Clinical trial NCT03149549
Conditions: Solid Tumor, Adult Breast Cancer Non Small Cell Lung Cancer Head and Neck Cancer Ovarian Cancer
Keywords: cancer solid tumor PROCLAIM CX-2009 PROBODY™ Therapeutic Drug Conjugate Antibody drug conjugate CD166
Sponsor: CytomX Therapeutics
Start date: 2017-06-01; Completion date: 2020-09-10
Enrollment: 99 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this first-in-human study of CX-2009 is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of CX-2009 in adult subjects with metastatic or locally advanced unresectable solid tumors. PROCLAIM: PRObody CLinical Assessment In Man CX-2009 clinical trial 001

PROBODY is a trademark of CytomX Therapeutics, Inc

Detailed description:

Arms: arm 1: Dose escalation and determination arm 2: Additional enrollment into previously cleared monotherapy dose levels arm 3: Dose expansion arm 4: Dose escalation and determination in selected tumor types
Interventions: intervention 1: CX-2009
Intervention descriptions: intervention 1: CX-2009 Monotherapy

Protocol documents:
Prot_000.pdf: 
CTMX-M-2009-001 
A Phase 1-2, Open-Label, Dose-Finding, Proof of Concept, First-in-Human Study to Evaluate 
the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CX-2009 in Adults With 
Metastatic or Locally Advanced Unresectable Solid Tumors (PROCLAIM-CX-2009) 
NCT# NCT03149549 
20/February/2020 


PROCLAIM CLINICAL STUDY
MODULE CX-2009
A Phase 1-2, Open-Label, Dose-Finding, Proof of Concept, First-in-Human 
Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and 
Pharmacodynamics of CX-2009 in Adults With Metastatic or Locally 
Advanced Unresectable Solid Tumors
(PROCLAIM-CX-2009)
Investigational Product:
CX-2009
Module Number:
CTMX-M-2009-001
IND Number:
130533
EudraCT Number:
2017-000625-12
Sponsor:
CytomX Therapeutics, Inc.
151 Oyster Point Boulevard, Suite 400
South San Francisco, CA 94080-1913
Telephone: +1-650-515-3185
Fax:
+1-650-351-0353
Medical Monitor/
Medical Expert:
Alison L. Hannah, MD
Chief Medical Officer
Clinical Development
CytomX Therapeutics, Inc.
Telephone: +1-650-383-0702
Fax:
+1-650-351-0353
Date of Original Module (v1.0): 13 April 2017
Date of Amendment 1 (v2.0):
15 May 2017
Date of Amendment 2:
31 October 2017
Date of Amendment 3:
09 March 2018
Date of Amendment 4:
10 September 2018
Date of Amendment 5:
13 February 2019
Date of Amendment 6:
09 August 2019
Date of Amendment 6.1:
16 December 2019
Date of Amendment 7:
20 February 2020
CONFIDENTIALITY STATEMENT
The information in this document is confidential and is not to be disclosed without the written consent of 
CytomX Therapeutics, Inc., except to the extent that disclosure would be required by law and for the purpose of 
evaluating and/or conducting a clinical study for CytomX Therapeutics, Inc. You are allowed to disclose the 
contents of this document only to your Institutional Review Board or Independent Ethics Committee and to study 
personnel directly involved with conducting this Module. Persons to whom the information is disclosed must be 
informed that the information is confidential and proprietary to CytomX Therapeutics, Inc., and that it may not be 
further disclosed to third parties.




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INVESTIGATOR AGREEMENT
By signing below I agree that:
I have read the contents of the Common Core Document CTMX-C-001,
Module CTMX-M-2009-001, and any subsequent amendments. I will provide copies of these 
documents, and access to all information furnished by CytomX Therapeutics, Inc. to all study 
personnel under my supervision. I will discuss this material with them to ensure they are fully 
informed about the study product and study procedures. I will let them know that this 
information is confidential and proprietary to CytomX Therapeutics, Inc., and that it may not be 
further disclosed to third parties. I understand that the study may be terminated or enrollment 
may be suspended at any time by CytomX Therapeutics, Inc., with or without cause, or by me if 
it becomes necessary to protect the health and well-being of the study subjects.
I agree to conduct this study in full accordance with: (i) the Common Core Document 
CTMX-C-001, Module CTMX-M-2009-001, and any subsequent amendments; (ii) applicable 
regulatory requirements; (iii) Institutional Review Board/Independent Ethics Committee 
regulations; and (iv) the International Council for Harmonisation Guidelines for Good Clinical 
Practices.
Investigator’s Signature
Date
Investigator’s Printed Name


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SYNOPSIS
TITLE
A Phase 1-2, Open-Label, Dose-Finding, Proof of Concept, First-in-Human Study to Evaluate the Safety, 
Tolerability, Pharmacokinetics, and Pharmacodynamics of CX-2009 in Adults With Metastatic or Locally 
Advanced Unresectable Solid Tumors (PROCLAIM-CX-2009)
MODULE NUMBER
CTMX-M-2009-001
INVESTIGATIONAL PRODUCT
CX-2009
PHASE
Phase 1-2
INDICATION(S)
Metastatic or locally advanced unresectable solid tumors
INTRODUCTION AND STUDY RATIONALE
CX-2009 is an antibody-based prodrug, referred to as a Probody™ therapeutic derived from a proprietary, 
humanized anti–cluster of differentiation 166 (CD166) monoclonal antibody (mAb), and conjugated to 
N-succinimidyl 4-(2-pyridyldithio) butanoate-N2c-deacetyl-N2c-(4-mercapto-4-methyl-1-oxopentyl)-
maytansine (DM4). CX-2009 has a drug to antibody ratio (DAR) of 3.5, similar to the DARs observed in 
other DM4 antibody-drug conjugates (ADCs) in clinical use. Expression, purification, DM4 conjugation, 
formulation, characterization, stability, and administration of CX-2009 are similar to those for other 
mAbs.
Probody therapeutics differ from unmodified mAbs by the recombinant addition of a prodomain at the 
amino-terminus of the light chain, which blocks the antibody binding to its target antigen and can be 
removed by tumor-associated protease activity. In this way, CX-2009 is expected to be activated in 
tumors and bind to its target CD166 but to be relatively inactive outside of the tumor microenvironment 
(TME). The substrate of CX-2009 is designed to be cleaved by a number of proteases associated with 
TMEs, including serine protease and matrix metalloproteinase classes. These proteases were chosen to 
activate CX-2009 because of their association with the human TME. In numerous cell line xenograft and 
patient-derived xenograft tumor models, treatment with CX-2009 has led to significant tumor growth 
inhibition or regression. It was also observed that, at the anticipated therapeutic dose levels, CX-2009
shows extended exposure in cynomolgus monkeys compared with the corresponding CD166-targeting 
ADC, consistent with CX-2009 avoidance of the antigen sink in normal tissues. Together, these results 
indicate that CX-2009 can be efficiently activated in the tumor, while maintaining low binding to normal 
tissues.
Parts A, B, and C of the study will test CX-2009 administered as monotherapy. Parts D and E will test the 
combination of CX-2009 plus CX-072, a Probody therapeutic directed against programmed death ligand 1 
(PD-L1), with the rationale that the combination of a maytansinoid ADC and an anti–PD-L1 antibody has 
the potential to produce durable clinical benefit. The rationale for the combination of an ADC with 
immune checkpoint inhibitor (ICI) is presented in Section 1.6, including non-clinical data combining 
CX-2009 with CX-072. Briefly, ADCs have been demonstrated to kill cancer cells, resulting in 


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immunogenic cell death. In addition, the cytotoxic payload may provide phenotypic and functional 
dendritic cell maturation and activation in a manner that may potentiate the activity of ICIs. Clinical trials 
investigating an ADC (such as ado-trastuzumab emtansine) in combination with an ICI (such as 
atezolizumab) are on-going. CX-2009 administered every 14 days and every 21 days as monotherapy and 
in combination with CX-072 will be evaluated in order to optimize the dosing regimen and facilitate other 
potential combination evaluations.
This study is composed of 2 distinct documents:
x
A common core (“Core”; see separate synopsis [Appendix A]), and 
x
A CX-2009-specific module (“Module”; this document).
Briefly, the Core is a stable document that contains all the design features typically included in a standard 
Phase 1-2 protocol, but without reference to a specific experimental agent. The exact same core document 
is used for all Probody therapeutic first in human (FIH) studies, serving as a centerpiece for all Probody 
therapeutics in development. It includes, for example, guidelines for drug accountability, efficacy and 
safety parameters, and study administrative procedures. The CX-2009 Module (this current document), on 
the other hand, is customized for this specific Probody therapeutic, and all protocol guidelines necessary 
to safely manage subject care are included within the Module. Familiarity with both the Core and the 
CX-2009 Module is required for proper conduct of the study.
The Core plus Module system is a mechanism for bundling the clinical evaluation of Probody
therapeutics within 1 unified program, with a common study design and common Investigator oversight. 
See the Core synopsis for a more detailed discussion of the Core design and rationale.
OBJECTIVES
Primary Objectives
Part A – CX-2009 Monotherapy: Every 21-Day Dosing Regimen
The primary objective of Part A is to determine the safety profile of CX-2009, the maximum tolerated 
dose (MTD)/recommended Phase 2 dose (RP2D), and the dose-limiting toxicities (DLTs) of CX-2009
when administered intravenously (IV) every 21 days as monotherapy to subjects with selected advanced 
or recurrent solid tumors. 
Part A2 – CX-2009 Monotherapy: Every 21-Day Dosing Regimen
The primary objectives of Part A2 are to determine the following in subjects treated with CX-2009 every 
21 days:
x
Characterize the protease activity and measure the cleavage of CX-2009 in tumor biopsies and 
peripheral blood; and
x
Obtain additional characterization of the safety of CX-2009 when administered as monotherapy at 
dose levels evaluated in Part A.
Part B – CX-2009 Monotherapy: Every 21-Day Dosing Regimen
The primary objective of Part B is to evaluate the efficacy of CX-2009 when administered IV every 
21 days as monotherapy at the MTD/RP2D (as defined in consideration of available data from Part A and 
Part A2) in subjects with selected advanced or recurrent solid tumors. Efficacy will be assessed on the 
basis of the objective response rate (ORR) by the Response Evaluation Criteria in Solid Tumours 
(RECIST) Version 1.1.


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Part C1 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen
The primary objective of Part C1 is to determine the safety profile of CX-2009, the MTD/RP2D, and the 
DLTs of CX-2009 when administered IV every 14 days as monotherapy to subjects with selected 
advanced or recurrent solid tumors.
Part C2 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen
The primary objective of Part C2 is to evaluate the efficacy of CX-2009 when administered IV every 
14 days as monotherapy at the MTD/RP2D to subjects with selected advanced or recurrent solid tumors.
Efficacy will be assessed on the basis of the ORR by the RECIST Version 1.1.
Part D1 – CX-2009 + CX-072 Combination: Every 14-Day Dosing Regimen
The primary objective of Part D1 is to determine the safety profile, the MTD/RP2D, and the DLTs of 
CX-2009 in combination with CX-072, both administered IV every 14 days to subjects with selected 
advanced or recurrent solid tumors.
Part D2 – CX-2009 + CX-072 Combination: Every 14-Day Dosing Regimen
The primary objective of Part D2 is to evaluate the efficacy of CX-2009 in combination with CX-072, 
both administered IV every 14 days at the MTD/RP2D to subjects with selected advanced or recurrent 
solid tumors. Efficacy will be assessed on the basis of ORR per RECIST Version 1.1.
Part E1 – CX-2009 + CX-072 Combination: Every 21-Day Dosing Regimen
The primary objective of Part E1 is to determine the safety profile, the MTD/RP2D, and the DLTs of 
CX-2009 in combination with CX-072, both administered IV every 21 days to subjects with selected 
advanced or recurrent solid tumors.
Part E2 – CX-2009 + CX-072 Combination: Every 21-Day Dosing Regimen
The primary objective of Part E2 is to evaluate the efficacy of CX-2009 in combination with CX-072, 
both administered IV every 21 days at the MTD/RP2D to subjects with selected advanced or recurrent 
solid tumors. Efficacy will be assessed on the basis of ORR per RECIST Version 1.1.
Secondary Objectives
Part A – CX-2009 Monotherapy: Every 21-Day Dosing Regimen
The secondary objectives of Part A are to determine the following in subjects treated with CX-2009 every 
21 days:
x
Evaluate preliminary efficacy in subjects treated with CX-2009 as monotherapy on the basis of:
— ORR by the RECIST Version 1.1;
— Time to tumor response (TTR);
— Duration of response (DOR); 
— Progression-free survival (PFS); and
— Overall survival (OS);
x
Characterize the pharmacokinetics (PK) of CX-2009 with respect to the following analytes:
— Intact CX-2009 (referring to the prodrug form of CX-2009 r DM4);
— Total CX-2009 (intact and activated forms of CX-2009 r DM4);
— Total CX-2009-conjugated DM4 (antibody conjugated-DM4);


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— Free DM4; and
— S-methyl DM4 (DM4-Me) - a DM4 metabolite with potent cytotoxic activity; and 
x
Assess the incidence of antidrug antibody (ADA) formation to CX-2009.
Part A2 – CX-2009 Monotherapy: Every 21-Day Dosing Regimen
The secondary objectives of Part A2 are to determine the following in subjects treated with CX-2009
every 21 days:
x
Evaluate preliminary efficacy in subjects treated with CX-2009 as monotherapy on the basis of:
— ORR by the RECIST Version 1.1;
— TTR;
— DOR;
— PFS; and
— OS;
x
Characterize the PK of CX-2009 with respect to the following analytes:
— Intact CX-2009 (referring to the prodrug form of CX-2009 r DM4);
— Total CX-2009 (intact and activated forms of CX-2009 r DM4);
— Total CX-2009-conjugated DM4 (antibody conjugated-DM4);
— Free DM4; and
— DM4-Me; and 
x
Assess the incidence of ADA formation to CX-2009. 
Part B – CX-2009 Monotherapy: Every 21-Day Dosing Regimen
The secondary objectives of Part B are to determine the following in subjects treated with CX-2009 every 
21 days:
x
Obtain additional characterization of the safety of CX-2009 at the MTD/RP2D;
x
Evaluate efficacy in subjects treated with CX-2009 as monotherapy on the basis of:
— DOR; 
— TTR;
— PFS; and
— OS;
x
Characterize the PK of CX-2009 with respect to the following analytes:
— Intact CX-2009 (referring to the prodrug form of CX-2009 r DM4);
— Total CX-2009 (intact and activated forms of CX-2009 r DM4);
— Total CX-2009-conjugated DM4 (antibody conjugated-DM4);
— Free DM4; and
— DM4-Me; and
x
Assess the incidence of ADA formation to CX-2009.


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Part C1 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen
The secondary objectives of Part C1 are to determine the following in subjects treated with CX-2009
every 14 days:
x
Evaluate preliminary efficacy in subjects treated with CX-2009 as monotherapy on the basis of:
— ORR by the RECIST Version 1.1;
— TTR;
— DOR;
— PFS; and
— OS;
x
Characterize the PK of CX-2009 with respect to the following analytes:
— Intact CX-2009 (referring to the prodrug form of CX-2009 r DM4);
— Total CX-2009 (intact and activated forms of CX-2009 r DM4);
— Total CX-2009-conjugated DM4 (antibody conjugated-DM4);
— Free DM4; and
— DM4-Me; and
x
Assess the incidence of ADA formation to CX-2009.
Part C2 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen
The secondary objectives of Part C2 are to determine the following in subjects treated with CX-2009
every 14 days:
x
Obtain additional characterization of the safety of CX-2009 at the MTD/RP2D;
x
Evaluate efficacy in subjects treated with CX-2009 as monotherapy on the basis of:
— DOR;
— TTR;
— PFS; and
— OS;
x
Characterize the PK of CX-2009 with respect to the following analytes:
— Intact CX-2009 (referring to the prodrug form of CX-2009 r DM4);
— Total CX-2009 (intact and activated forms of CX-2009 r DM4);
— Total CX-2009-conjugated DM4 (antibody conjugated-DM4);
— Free DM4; and
— DM4-Me; and
x
Assess the incidence of ADA formation to CX-2009.
Part D1 – CX-2009 + CX-072 Combination: Every 14-Day Dosing Regimen
The secondary objectives of Part D1 are to determine the following in subjects treated with CX-2009 plus 
CX-072 every 14 days:
x
Evaluate preliminary efficacy in subjects treated with CX-2009 plus CX-072 on the basis of:
— ORR by the RECIST Version 1.1;
— ORR by immune-related RECIST (irRECIST) as defined in the Core;
— TTR;


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— DOR;
— PFS; and
— OS;
x
Characterize the PK of CX-2009 when it is administered in combination with CX-072 with respect to 
the following analytes:
— Intact CX-2009 (referring to the prodrug form of CX-2009 r DM4);
— Total CX-2009 (intact and activated forms of CX-2009 r DM4);
— Total CX-2009-conjugated DM4 (antibody conjugated-DM4);
— Free DM4; and
— DM4-Me; 
x
Assess the incidence of ADA formation to CX-2009 when it is administered in combination with 
CX-072;
x
Characterize the PK profile of CX-072 when it is administered in combination with CX-2009; and
x
Assess the incidence of ADA formation to CX-072 when it is administered in combination with 
CX-2009.
Part D2 – CX-2009 + CX-072 Combination: Every 14-Day Dosing Regimen
The secondary objectives of Part D2 are to determine the following in subjects treated with CX-2009 plus 
CX-072 every 14 days:
x
Obtain additional characterization of the safety of CX-2009 administered with CX-072 at the 
MTD/RP2D;
x
Evaluate efficacy in subjects treated with CX-2009 plus CX-072 on the basis of:
— DOR;
— TTR;
— PFS;
— OS; and
— ORR by irRECIST as defined in the Core;
x
Characterize the PK of CX-2009 when it is administered in combination with CX-072 with respect to 
the following analytes:
— Intact CX-2009 (referring to the prodrug form of CX-2009 r DM4);
— Total CX-2009 (intact and activated forms of CX-2009 r DM4);
— Total CX-2009-conjugated DM4 (antibody conjugated-DM4);
— Free DM4; and
— DM4-Me; 
x
Assess the incidence of ADA formation to CX-2009 when it is administered in combination with 
CX-072;
x
Characterize the PK profile of CX-072 when it is administered in combination with CX-2009; and
x
Assess the incidence of ADA formation to CX-072 when it is administered in combination with 
CX-2009.


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Part E1 – CX-2009 + CX-072 Combination: Every 21-Day Dosing Regimen
The secondary objectives of Part E1 are to determine the following in subjects treated with CX-2009 plus 
CX-072 every 21 days:
x
Evaluate preliminary efficacy in subjects treated with CX-2009 plus CX-072 on the basis of:
— ORR by the RECIST Version 1.1;
— ORR by irRECIST as defined in the Core;
— TTR;
— DOR;
— PFS; and
— OS;
x
Characterize the PK of CX-2009 when it is administered in combination with CX-072 with respect to 
the following analytes:
— Intact CX-2009 (referring to the prodrug form of CX-2009 r DM4);
— Total CX-2009 (intact and activated forms of CX-2009 r DM4);
— Total CX-2009-conjugated DM4 (antibody conjugated-DM4);
— Free DM4; and
— DM4-Me; 
x
Assess the incidence of ADA formation to CX-2009 when it is administered in combination with 
CX-072;
x
Characterize the PK profile of CX-072 when it is administered in combination with CX-2009; and
x
Assess the incidence of ADA formation to CX-072 when it is administered in combination with 
CX-2009.
Part E2 – CX-2009 + CX-072 Combination: Every 21-Day Dosing Regimen
The secondary objectives of Part E2 are to determine the following in subjects treated with CX-2009 plus 
CX-072 every 21 days:
x
Obtain additional characterization of the safety of CX-2009 administered with CX-072 at the 
MTD/RP2D;
x
Evaluate efficacy in subjects treated with CX-2009 plus CX-072 on the basis of:
— DOR;
— TTR;
— PFS;
— OS; and
— ORR by irRECIST as defined in the Core;
x
Characterize the PK of CX-2009 when it is administered in combination with CX-072 with respect to 
the following analytes:
— Intact CX-2009 (referring to the prodrug form of CX-2009 r DM4);
— Total CX-2009 (intact and activated forms of CX-2009 r DM4);
— Total CX-2009-conjugated DM4 (antibody conjugated-DM4);
— Free DM4; and
— DM4-Me; 


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x
Assess the incidence of ADA formation to CX-2009 when it is administered in combination with 
CX-072;
x
Characterize the PK profile of CX-072 when it is administered in combination with CX-2009; and
x
Assess the incidence of ADA formation to CX-072 when it is administered in combination with 
CX-2009.
Exploratory Objectives
Part A – CX-2009 Monotherapy: Every 21-Day Dosing Regimen
The exploratory objectives of Part A are to determine the following in subjects treated with CX-2009
every 21 days:
x
Explore potential predictive markers associated with CX-2009 clinical activity such as CD166 
expression in tumor specimens prior to and while receiving treatment; and
x
Characterize the protease activity in optional pretreatment tumor biopsies and activation of CX-2009
in optional on-treatment tumor biopsies and peripheral blood.
Part A2 – CX-2009 Monotherapy: Every 21-Day Dosing Regimen
The exploratory objectives of Part A2 are to determine the following in subjects treated with CX-2009
every 21 days:
x
Evaluate the relationship between CX-2009 dose and exposure, exploratory biomarkers, safety, and 
efficacy of CX-2009 as monotherapy in subjects with selected advanced or recurrent solid tumors; 
and
x
Explore potential predictive markers associated with CX-2009 clinical activity such as CD166 
expression in tumor specimens while receiving treatment.
Part B – CX-2009 Monotherapy: Every 21-Day Dosing Regimen
The exploratory objectives of Part B are to determine the following in subjects treated with CX-2009
every 21 days:
x
Explore potential predictive markers associated with CX-2009 clinical activity such as CD166 
expression in tumor specimens prior to and while receiving treatment;
x
Measure the intact and activated CX-2009 in on-treatment tumor biopsies and peripheral blood; and 
x
Characterize the protease activity in pretreatment tumor biopsies.
Part C1 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen
The exploratory objectives of Part C1 are to determine the following in subjects treated with CX-2009
every 14 days:
x
Explore potential predictive markers associated with CX-2009 clinical activity such as CD166 
expression in tumor specimens prior to and while receiving treatment; and
x
Characterize the protease activity in optional pretreatment tumor biopsies and activation of CX-2009
in optional on-treatment tumor biopsies and peripheral blood.


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Part C2 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen
The exploratory objectives of Part C2 are to determine the following in subjects treated with CX-2009
every 14 days:
x
Explore potential predictive markers associated with CX-2009 clinical activity such as CD166 
expression in tumor specimens prior to and while receiving treatment; and
x
Characterize the activation of CX-2009 in on-treatment tumor biopsies and peripheral blood.
Part D1 – CX-2009 + CX-072 Combination: Every 14-Day Dosing Regimen
The exploratory objectives of Part D1 are to determine the following in subjects treated with CX-2009
plus CX-072 every 14 days:
x
Explore potential predictive markers associated with clinical activity of the treatment combination 
such as CD166 expression and PD-L1 status in tumor specimens prior to and while receiving 
treatment;
x
Characterize the protease activity and the activation of CX-2009 and CX-072 in optional on-treatment 
tumor biopsies and peripheral blood; and
x
Investigate the immunomodulatory activity of the treatment combination in optional on-treatment 
tumor biopsies (fixed and frozen).
Part D2 – CX-2009 + CX-072 Combination: Every 14-Day Dosing Regimen
The exploratory objectives of Part D2 are to determine the following in subjects treated with CX-2009
plus CX-072 every 14 days:
x
Explore potential predictive markers associated with clinical activity of the treatment combination 
such as CD166 expression and PD-L1 status in tumor specimens prior to and while receiving 
treatment;
x
Characterize the protease activity and the activation of CX-2009 and CX-072 in optional on-treatment 
tumor biopsies and peripheral blood; and
x
Investigate the immunomodulatory activity of the treatment combination in optional on-treatment 
tumor biopsies (fixed and frozen).
Part E1 – CX-2009 + CX-072 Combination: Every 21-Day Dosing Regimen
The exploratory objectives of Part E1 are to determine the following in subjects treated with CX-2009
plus CX-072 every 21 days:
x
Explore potential predictive markers associated with clinical activity of the treatment combination 
such as CD166 expression and PD-L1 status in tumor specimens prior to and while receiving 
treatment;
x
Characterize the protease activity and the activation of CX-2009 and CX-072 in optional on-treatment 
tumor biopsies and peripheral blood; and
x
Investigate the immunomodulatory activity of the treatment combination in optional on-treatment 
tumor biopsies (fixed and frozen).


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Part E2 – CX-2009 + CX-072 Combination: Every 21-Day Dosing Regimen
The exploratory objectives of Part E2 are to determine the following in subjects treated with CX-2009
plus CX-072 every 21 days:
x
Explore potential predictive markers associated with clinical activity of the treatment combination 
such as CD166 expression and PD-L1 status in tumor specimens prior to and while receiving 
treatment;
x
Characterize the protease activity and the activation of CX-2009 and CX-072 in optional on-treatment 
tumor biopsies and peripheral blood; and
x
Investigate the immunomodulatory activity of the treatment combination in optional on-treatment 
tumor biopsies (fixed and frozen).
STUDY DESIGN
This is a Phase 1-2, open-label, multicenter, dose-finding, and proof of concept study for CX-2009 as 
monotherapy and (where permitted by local Health Authority) in combination with CX-072 in subjects 
with advanced solid tumors in the following indications: breast cancer (BC), castrate-resistant prostate 
carcinoma (CRPC), non-small cell lung carcinoma (NSCLC), ovarian epithelial cancer (OEC), 
endometrial carcinoma (EC), head and neck squamous cell carcinoma (HNSCC), or cholangiocellular 
carcinoma (CCC). See Table 4 for an overview of the eligible tumor types and enrollment numbers for 
each part. These tumor types have been selected for their known high levels of CD166 expression and 
sensitivity to microtubule inhibitors (MTIs).
The study is divided into 9 parts: Parts A, A2, B, C1, C2, D1, D2, E1, and E2 (see Figure 4), each 
designed to inform dose selection for the next phase of development. Part A is designed to define the 
MTD in 2 separate stages: a standard 3+3 escalation followed by a modified toxicity probability interval 2 
(mTPI-2) cohort, in subjects receiving CX-2009 every 21 days. Part A2 is designed for biomarker 
evaluation (particularly Probody therapeutic activation) in order to further inform dose optimization. 
Part B is focused on expanding clinical experience in order to further define the safety profile at the 
MTD/RP2D as well as to obtain a preliminary assessment of efficacy in a select number of cancers. 
Part B may be initiated as soon as the MTD/RP2D is defined in Part A and available data from Part A2 
are reviewed in consultation with the Safety Review Committee (SRC; see Appendix E). Part C1 is 
designed to define the MTD/RP2D in subjects receiving CX-2009 every 14 days. Part C2 is focused on 
expanding clinical experience in order to further define the safety profile of CX-2009 and to obtain a 
preliminary assessment of efficacy when administered every 14 days at the MTD/RP2D. Dose expansion 
for CX-2009 monotherapy may occur under the every 21-day dosing regimen (Part B) and/or the every 
14-day dosing regimen (Part C2), depending on available data from Parts A, A2, and C1.
Parts D and E involve co-administration of CX-2009 and CX-072. As such, these cohorts are only open to
those countries in which the Health Authority permits these cohorts to activate. Part D1 is designed to
define the MTD/RP2D in subjects receiving CX-2009 in combination with CX-072 every 14 days. 
Part D2 is focused on expanding clinical experience to further define the safety profile of CX-2009
administered in combination with CX-072 and to obtain a preliminary assessment of efficacy of the 
combination when administered every 14 days at the MTD/RP2D. Part E1 is designed to define the 
MTD/RP2D in subjects receiving CX-2009 in combination with CX-072 every 21 days. Part E2 is 
focused on expanding clinical experience to further define the safety profile of CX-2009 administered in 
combination with CX-072 and to obtain a preliminary assessment of efficacy of the combination when 
administered every 21 days at the MTD/RP2D.


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Part A: 
Dose escalation and determination of the MTD/RP2D of the CX-2009 monotherapy every 21-day 
dosing regimen (n d 79: based on actual enrollment of initial cohorts and assumption of remaining 
cohorts and up to 38 total subjects enrolled into the mTPI-2 design cohort)
This part initiates with accelerated dose titration in 1 single-subject cohort (0.25 mg/kg, adjusted ideal 
body weight [AIBW]), followed by a standard 33 design to determine the MTD, and ends in an mTPI-2
design cohort with up to 38 subjects with demonstrated high CD166 expression to determine the RP2D. 
The mTPI-2 design is a rule-based design similar to the 33 design and allows dose 
escalation/de-escalation. It is assumed to be of similar accuracy in determining the optimal dose as 
model-based design (Ji 2007) but allows a more flexible sample size. To understand the statistical 
rationale for the design, please refer to Section 9 and Appendix C.
One subject will be enrolled into the first cohort until the first dose level is enrolled and treated 
successfully. Should a subject in cohort 1 experience a tGrade 2 adverse event (AE) that is at least 
possibly related to the study drug, 2 more subjects will be enrolled at that dose level and evaluated based 
on 33 design rules. Should the first subject in cohort 1 experience a DLT, the dose level will be 
expanded to 3 subjects and if there is no additional DLT, the dose level will be expanded to 6 subjects. 
All subsequent cohorts will utilize a 33 design and will enroll sufficient evaluable subjects to allow for 
DLT evaluation. Dosing increments will be less than 100.0% if a subject in the single-subject cohort 
experiences a tGrade 2 toxicity. The first subject in each new dose cohort will be dosed at least 24 hours 
prior to any other subjects in that cohort being dosed, to allow for observation of possible severe and/or 
serious acute (eg, infusion-related) toxicities that might affect subsequent subject enrollment or dosing 
decisions. 
Enrollment will continue in each cohort until the MTD or the RP2D is defined, or the highest dose 
(ie, 10 mg/kg, AIBW) has been tested and deemed safe, whichever is lower. AIBW should be applied 
using the formula provided in Appendix F.
Once the MTD is defined or the highest dose is tested (ie, 10 mg/kg, AIBW), up to 38 subjects can be 
enrolled at the MTD to refine dose selection using mTPI-2, a rule-based design similar to the 3+3 design 
that allows dose escalation/de-escalation. Up to 6 subjects can be treated at each dose level and up to 
14 subjects can be treated at the identified MTD/RP2D dose level. Assuming that up to 5 dose levels 
(6 mg/kg to 10 mg/kg, AIBW) may be explored in the mTPI-2 cohort, a maximum sample size of 
38 subjects may be enrolled. AEs that meet DLT criteria (within the 21-day DLT period) and delayed 
AEs that lead to treatment interruption/discontinuation within the first 6 weeks, thus encompassing the 
first 3 doses (DLT rate d30.0%; delayed AE rate d20.0%), will be monitored. Decision for dose 
escalation/de-escalation will be made by the Sponsor in consultation with the SRC guided by the 
decision-making table (Appendix C). The selection of MTD/RP2D will be based predominantly on safety 
and may take other factors into account such as PK/pharmacodynamics (PD) and clinical activity. 
Subjects may be permitted individual dose escalations to previously cleared dose levels following 
consultation with the Medical Monitor.
The DLT assessment period for dose escalation is 21 days. 
Part A2: 
Additional enrollment into previously cleared CX-2009 monotherapy dose levels from Part A 
(n d 42) for every 21-day dosing regimen
Part A2 will help to inform selection of the optimal MTD/RP2D by requiring measurable disease,
mandating tumor biopsies to assess Probody therapeutic CX-2009 performance, and selecting for 
confirmed high CD166 expressing tumors by immunohistochemistry.


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Part A2 will initiate enrollment after the 4 mg/kg cohort in Part A has completed the DLT period and with 
the recommendation of the SRC. Six subjects must be enrolled into each cohort before the next sequential 
cohort can be enrolled. Doses administered in Part A2 can never exceed the most recently cleared dose in 
Part A. All toxicities observed in Part A2, regardless of whether they are observed early or late in the 
dosing course, will be reviewed by the SRC and used to make recommendations for further enrollment in 
all parts of the study.
Up to a total of 42 subjects will be enrolled at up to 7 dose levels with 6 subjects per cohort per dose. 
Available data from Part A2 will be considered by the SRC when making dosing recommendations and 
performing cohort review in Part A. As of November 2019, the RP2D for further study of CX-2009
monotherapy when given every 21 days in Part B was determined to be 7 mg/kg; this dose will continue 
to be assessed for safety and may be modified if supported by the data.
Part A2 will be restricted to subjects with BC, NSCLC, OEC, EC, and HNSCC. These tumor types have 
been selected for their responsiveness to MTIs and general availability of lesion safe to be biopsied.
Tumor biopsies are required 3 to 5 days after the first dose of CX-2009. To enroll a subject in Part A2, the 
Investigator must consider the subject safe to biopsy and the subject must consent to biopsy collection.
Part B: 
Dose expansion (proof of concept) at the MTD/RP2D of CX-2009 monotherapy every 21-day dosing 
regimen with proof of concept in selected tumor types (maximum n d 200)
Part B will explore efficacy of CX-2009 by requiring measurable disease. Part B will enroll up to a total 
of 40 subjects each in 1 or more of the following indications: triple-negative breast cancer (TNBC), 
hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative BC, 
NSCLC, OEC, or HNSCC. As of November 2019, Part B will be initiated in subjects with 
HR-positive/HER2-negative BC at a dose of 7 mg/kg.
Part C1: 
Dose escalation/de-escalation and determination of the MTD/RP2D of the CX-2009 monotherapy 
every 14-day dosing regimen (n d 24)
The highest dose level tested in this clinical study for CX-2009 was 10 mg/kg administered every
21 days, which successfully cleared the DLT evaluation period. The every 14-day dosing regimen 
equivalent of 10 mg/kg administered every 21 days is t7 mg/kg. In order to provide an additional margin 
of safety coverage for Part C1, the starting dose was 6 mg/kg, AIBW, administered every 14 days. The 
initial starting dose for Part C1 was not determined to be tolerated (see Section 1.3.4.1); a lower dose 
(4 mg/kg) will therefore be explored on the every 14-day schedule. Subsequent dose 
escalation/de-escalation (if any) will be based upon the observed safety tolerability profile as determined 
in consultation with the SRC. Prior to a dose escalation/de-escalation, a minimum of 3 evaluable subjects 
must be assessed (Figure 6). Part C1 will include up to 24 subjects. Subjects will be selected from the 
following indications: TNBC, HR-positive/HER2-negative BC, NSCLC, OEC, or HNSCC.
AEs that meet DLT criteria (within the 28-day DLT period) and delayed AEs that lead to treatment 
interruption/discontinuation within the first 6 weeks, thus encompassing the first 3 doses (DLT rate 
d30.0%; delayed AE rate d20.0%), will be monitored. Decision for dose escalation/de-escalation will be 
made by the Sponsor in consultation with the SRC guided by the decision-making table (Appendix C). 
The selection of MTD/RP2D at an every 14-day dosing regimen will be based predominantly on safety 
and may take other factors into account such as PK/PD and clinical activity.
Subjects who discontinue study drug administration for reasons other than DLTs may be replaced to 
ensure the minimum number of subjects required for DLT evaluation is enrolled.


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Part C2: 
Dose expansion at the MTD/RP2D of CX-2009 monotherapy every 14-day dosing regimen in 
selected tumor types (maximum n d 200)
Part C2 will explore efficacy of CX-2009. Part C2 will enroll up to a total of 40 subjects each in 1 or 
more of the following indications: TNBC, HR-positive/HER2-negative BC, NSCLC, OEC, or HNSCC. 
These tumor types have been selected for their responsiveness to MTIs and general availability of lesion 
safe to be biopsied. 
Part C2 may be initiated as soon as the MTD/RP2D for the 14-day regimen is defined in consultation with 
the SRC and will only be initiated if, after the review of dose escalation data (Part C1), an every 14-day 
dosing regimen is considered for further development.
Part D1: 
Dose escalation/de-escalation and determination of the MTD/RP2D for the CX-2009 + CX-072 
combination in an every 14-day dosing regimen in selected tumor types (n d 24)
Part D1 is only open to those countries in which the Health Authority permits the combination of 
CX-2009 and CX-072 to be investigated. The dose of CX-072 will be fixed at the RP2D (800 mg every 
14 days). The starting dose for CX-2009 will be set at the every 14-day monotherapy RP2D as determined 
in Part C1. Lower starting doses may be used based on emerging safety data and in consultation with the 
SRC. The mTPI-2 design will be used to determine the MTD/RP2D for the combination dosed every 
14 days. The following cohort’s dose will be increased or decreased according to the defined dose 
escalation rules based upon the observed safety tolerability profile as determined in consultation with the 
SRC. Prior to a dose escalation/de-escalation, a minimum of 3 evaluable subjects must be assessed per the 
mTPI-2 algorithm (Figure 6). Part D1 will enroll subjects in 1 or more of the following indications: 
TNBC, HR-positive/HER2-negative BC, NSCLC, OEC, or HNSCC.
Part D1 will evaluate dose levels based on DLT events and treatment-related AEs leading to treatment 
delay or discontinuation, including events of special interest (eg, ocular toxicity and peripheral 
neuropathy).
AEs that meet DLT criteria (within the 28-day DLT period) and delayed AEs that lead to treatment 
interruption/discontinuation within the first 6 weeks, thus encompassing the first 3 doses (DLT rate 
d30.0%; delayed AE rate d20.0%), will be monitored. Decision for dose escalation/de-escalation will be 
made by the Sponsor in consultation with the SRC guided by the decision-making table (Appendix C). 
The selection of MTD/RP2D will be based predominantly on safety and may take other factors into 
account such as PK/PD and clinical activity.
Subjects who discontinue study drug administration for reasons other than DLTs may be replaced to 
ensure the minimum number of subjects required for DLT evaluation is enrolled.
Part D2: 
Dose expansion at the MTD/RP2D of the CX-2009 + CX-072 combination in an every 14-day dosing 
regimen in selected tumor types (maximum n d 200) 
Part D2 is only open to those countries in which the Health Authority permits the combination of 
CX-2009 and CX-072 to be investigated. Part D2 will explore efficacy of CX-2009 plus CX-072 for the 
every 14-day dosing regimen at the dose selected in Part D1. Part D2 will enroll up to a total of 
40 subjects each in 1 or more of the following indications: TNBC, HR-positive/HER2-negative BC, 
NSCLC, OEC, or HNSCC. Part D2 may be initiated as soon as the MTD/RP2D for the 14-day 
combination regimen is defined in consultation with the SRC and will only be initiated if, after the review 
of dose escalation data (Part D1), an every 14-day combination dosing regimen is considered for further 
development.


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Part E1: 
Dose escalation and determination of the MTD/RP2D for the CX-2009 + CX-072 combination in an 
every 21-day dosing regimen in selected tumor types (n d 24)
Part E1 is only open to those countries in which the Health Authority permits the combination of 
CX-2009 and CX-072 to be investigated. The dose of CX-072 will be fixed at the RP2D (1200 mg every 
21 days). The starting dose of CX-2009 will be 7 mg/kg (the every 21-day monotherapy RP2D as 
determined in Parts A/A2). Lower starting doses may be used based on emerging data and in consultation 
with the SRC. The mTPI-2 design will be used to determine the MTD/RP2D for the combination dosed 
every 21 days. The following cohort’s dose will be increased or decreased according to the defined dose 
escalation rules based upon the observed safety tolerability profile as determined in consultation with the 
SRC. Prior to a dose escalation/de-escalation, a minimum of 3 evaluable subjects must be assessed per the 
mTPI-2 algorithm (Figure 6). Part E1 will enroll subjects in 1 or more of the following indications: 
TNBC, HR-positive/HER2-negative BC, NSCLC, OEC, or HNSCC. Part E1 will evaluate dose levels
based on DLT events and treatment-related AEs leading to treatment delay or discontinuation, including 
events of special interest (eg, ocular toxicity and peripheral neuropathy).
AEs that meet DLT criteria (within the 21-day DLT period) and delayed AEs that lead to treatment 
interruption/discontinuation within the first 6 weeks, thus encompassing the first 3 doses (DLT rate 
d30.0%; delayed AE rate d20.0%), will be monitored. Decision for dose escalation/de-escalation will be 
made by the Sponsor in consultation with the SRC guided by the decision-making table (Appendix C). 
The selection of MTD/RP2D will be based predominantly on safety and may take other factors into 
account such as PK/PD and clinical activity.
Subjects who discontinue study drug administration for reasons other than DLTs may be replaced to 
ensure the minimum number of subjects required for DLT evaluation is enrolled.
Part E2: 
Dose expansion at the MTD/RP2D of the CX-2009 + CX-072 combination in an every 21-day dosing 
regimen in selected tumor types (maximum n d 200) 
Part E2 is only open to those countries in which the Health Authority permits the combination of 
CX-2009 and CX-072 to be investigated. Part E2 will explore efficacy of CX-2009 plus CX-072 for the 
every 21-day dosing regimen at the dose selected in Part E1. Part E2 will enroll up to a total of 
40 subjects each in 1 or more of the following indications: TNBC, HR-positive/HER2-negative BC, 
NSCLC, OEC, or HNSCC. Part E2 may be initiated as soon as the MTD/RP2D for the 21-day 
combination regimen is defined in consultation with the SRC and will only be initiated if, after the review 
of dose escalation data (Part E1), an every 21-day combination dosing regimen is considered for further 
development.
Allocation of subjects between Parts C, D, and E: In case Parts C, D, and E are open for enrollment 
concurrently and subjects meet the eligibility criteria for all parts, the Sponsor in conjunction with the 
Principal Investigator will determine to which part the subjects are allocated. The Sponsor will determine 
which tumor types will be selected for additional evaluation for Parts B, C2, D2, and E2.
DOSAGE FORMS AND ROUTE OF ADMINISTRATION
CX-2009 will be supplied as a lyophilized powder (cake) in 25 mg vials to be reconstituted with 5 mL of 
sterile water for injection (WFI) to a final concentration of 5.0 mg/mL. CX-2009 will be administered as 
an IV infusion over 90 (r10) minutes with careful monitoring of infusion-related reactions (IRRs). The 
SRC can modify the infusion rate for any dose if a dGrade 2 IRR occurs or if it is deemed to improve safe 
administration of CX-2009. If a tGrade 3 IRR occurs, this Module may be amended.


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CX-072 drug product is currently being supplied as a sterile solution for IV administration. CX-072 is 
supplied in a 10 mL volume, and each vial contains 100 mg of CX-072 formulated with suitable 
compendial excipients. Upon regulatory approval, the CX-072 drug product is planned to be supplied as a 
lyophilized powder (cake) in single-use vials for reconstitution with sterile WFI before IV administration. 
CX-072 is administered at a fixed dose of 800 mg over 60 (r10) minutes for Parts D1 and D2 and 
1200 mg over 60 (r10) minutes for Parts E1 and E2.
When CX-2009 and CX-072 are administered on the same day, CX-072 is to be administered first, followed 
by a saline flush, followed by the CX-2009 infusion. CX-2009 is to be infused no sooner than 30 minutes 
after completion of the CX-072 infusion.
EFFICACY VARIABLES 
The primary criteria for defining evidence of anticancer activity and also for management of subject care 
will be a clinical response as defined by RECIST (Version 1.1). Efficacy in subjects treated with the 
combination CX-2009 plus CX-072 (Parts D1, D2, E1, and E2) will be explored additionally on the basis 
of ORR by irRECIST as defined in the Core (Appendix A). Management of subjects in Parts D1, D2, E1, 
and E2 may also take into consideration tumor response assessed by irRECIST.
PHARMACOKINETIC, IMMUNOGENICITY, AND EXPLORATORY BIOMARKER 
VARIABLES 
Pharmacokinetics
Concentration versus time data will be tabulated and plotted for the individual and mean CX-2009 (total 
and intact), CX-2009-conjugated DM4 and free DM4, and DM4-Me analytes and for total and intact 
CX-072 moieties. PK parameters, including area under the plasma concentration-time curve (AUC), 
maximal plasma concentration (Cmax), minimal plasma concentration (Cmin), clearance, and volume of 
distribution at steady state, will be calculated for CX-2009 (total and intact), DM4 (conjugated and free), 
and DM4-Me analytes as appropriate and as data allow. Additional parameters such as terminal 
elimination half-life and accumulation may be calculated, and dose proportionality will be assessed for 
subjects with sufficient data. Estimates for these parameters will be tabulated and summarized (eg, mean, 
standard deviation, and coefficient of variation). CX-072 (total and intact moieties) Cmax and Cmin will be 
tabulated individually and summarized using descriptive statistics (eg, mean, standard deviation, and 
coefficient of variation).
Additional exploratory model-based PK analyses may be conducted and the results of these analyses may 
be reported in a document separate from the clinical study report.
Exploratory Biomarkers
Probody therapeutics differ from unmodified mAbs by the recombinant addition of a prodomain at the 
amino-terminus of the light chain, which blocks the antibody binding to its target antigen and can be 
removed by tumor-associated protease activity. In this way, CX-2009 and CX-072 are expected to be 
activated in tumors and bind to their targets, CD166 and PD-L1 respectively, but to be relatively inactive 
outside of the TME. 
The overall goal of the biomarker portion of CTMX-M-2009-001 is to explore A) Probody therapeutic 
mechanistic proof of concept, and B) potential predictive markers associated with the clinical activity of 
CX-2009 alone or in combination with CX-072.


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Exploratory studies will include the evaluation of: 
x
Probody therapeutic activation in tumors and in blood;
x
The potential link between tumor markers, such as the target of CX-2009 (ie, CD166), the target of 
CX-072 (ie, PD-L1) and the biological activity of CX-2009 alone or in combination with CX-072; 
x
The potential link between exploratory biomarkers in blood and the biological activity of CX-2009 
alone or in combination with CX-072; and
x
The presence of activated proteases in the human TME capable of removing the peptide mask and 
thereby activating the Probody therapeutic.
In order to address the above objectives, tissue samples will be collected throughout the course of the 
study.
For Parts A and C1, pretreatment and on-treatment tumor biopsies will be optional. For the subjects who
consent, tumor biopsies will be collected during the Screening Period (baseline) and 3 to 5 days after the 
first dose of CX-2009, provided that the tumor is accessible and a biopsy is deemed safe by the treating 
physician.
For Part A2, tumor biopsies (fixed and frozen) are required 3 to 5 days after the first dose of CX-2009, 
provided that the tumor is accessible and a biopsy is deemed safe by the treating physician. 
For Parts B and C2, consent to pretreatment and on-treatment tumor biopsies will be mandatory in at 
least 7 subjects for each tumor type. For these subjects, tumor biopsies (fixed and frozen) will be 
collected during the Screening Period (baseline) and 3 to 5 days after the first dose of CX-2009, provided 
that the tumor is accessible and a biopsy is deemed safe by the treating physician.
For Parts D1, D2, E1, and E2, on-treatment tumor biopsies will be optional. For the subjects who
consent, tumor biopsies will be collected 3 to 5 days after the third dose, provided that the tumor is 
accessible and a biopsy is deemed safe by the treating physician.
SAFETY VARIABLES
Safety variables include the incidence and nature of DLTs, AEs, and serious adverse events (SAEs), as 
well as physical examinations, vital sign measurements, triplicate electrocardiograms, clinical laboratory 
evaluations, and treatment discontinuation due to toxicity. 
SAMPLE SIZE DETERMINATION
A maximum of 993 subjects will be enrolled into the study: Part A d79 subjects, Part A2 d42 subjects, 
Part B d200 subjects, Part C1 d24 subjects, Part C2 d200 subjects, Part D1 d24 subjects, 
Part D2 d200 subjects, Part E1d24 subjects, and Part E2d200 subjects. No more than 40 subjects will be 
enrolled with a given tumor type in each part. Dose expansion for CX-2009 monotherapy may occur
under the every 21-day dosing regimen (Part B) and/or the every 14-day dosing regimen (Part C2), 
depending on available data from Parts A, A2, and C1. Dose expansion for CX-2009 in combination with 
CX-072 may occur under the every 14-day dosing regimen (Part D2) and/or the every 21-day dosing 
regimen (Part E2), depending on available data from Parts D1 and E1. Selection of the regimen and tumor 
type for dose expansion will be made in consultation with the SRC.
Part A, dose escalation with an every 21-day dosing regimen, of the study consists of an accelerated 
titration design, followed by a 3+3 design, and ending in a cohort using the mTPI-2 design. During dose 
escalation (3+3 design), the exact sample size will be determined by the observed safety profile, which 
will determine the number of subjects per cohort and the number of cohorts. 
Once the MTD is defined or the highest dose is tested (ie, 10 mg/kg, AIBW), up to 38 subjects can be 
enrolled at the MTD to refine dose selection using mTPI-2, a rule-based design similar to the 3+3 design 


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that allows dose escalation/de-escalation. In November 2019, the selection of 7 mg/kg as the MTD/RP2D 
was made based on factors including safety, efficacy, and PK/PD, by the Sponsor with input from the 
SRC. 
Part B, with an every 21-day dosing regimen, is designed to provide a preliminary assessment of efficacy 
at the MTD/RP2D. Given the confirmed ORR seen to date in subjects with HR-positive/HER2-negative 
BC receiving monotherapy CX-2009 on the every 21-day schedule, a 2-stage enrollment design will no 
longer be incorporated. The SRC will continue to review on-going safety and efficacy data throughout the 
course of the clinical study. The sample size was selected to estimate the ORR. With 40 subjects treated, 
if 8 subjects have confirmed objective responses, the observed ORR will be 20% (90% CI: 10% - 33%); 
the lower bound of the 90% CI would therefore exclude an ORR of 10%.
Part C1, dose escalation/de-escalation using the mTPI-2 design with an every 14-day dosing regimen, 
will enroll up to 24 subjects (3 to 6 subjects at each dose level) for the purposes of MTD/RP2D decisions.
Part C2, with an every 14-day dosing regimen, is designed to provide a preliminary assessment of 
clinical activity at the MTD/RP2D. Once the MTD/RP2D is defined in Part C1, expansion cohorts of up 
to 40 subjects in selected tumor types will be enrolled as described in Part B to evaluate the antitumor 
activity using the MTD/RP2D in Part C2. A 2-stage design may be incorporated into this cohort.
Part D1, dose escalation/de-escalation using the mTPI-2 design for CX-2009 with an every 14-day 
dosing regimen in combination with CX-072, will enroll up to 24 subjects (3 to 6 subjects at each dose 
level) for the purposes of MTD/RP2D decisions. 
Part D2, dose expansion of CX-2009 plus CX-072 with an every 14-day dosing regimen, is designed to 
provide a preliminary assessment of clinical activity at the MTD/RP2D. Once the MTD/RP2D is defined 
in Part D1, expansion cohorts of 40 subjects in selected tumor types will be enrolled as described in 
Part B to evaluate the antitumor activity of CX-2009 plus CX-072. A 2-stage design may be incorporated 
into this cohort.
Part E1, dose escalation using the mTPI-2 design for CX-2009 with an every 21-day dosing regimen in 
combination with CX-072, will enroll up to 24 subjects (3 to 6 subjects at each dose level) for the 
purposes of MTD/RP2D decisions. 
Part E2, dose expansion of CX-2009 plus CX-072 with an every 21-day dosing regimen, is designed to 
provide a preliminary assessment of clinical activity at the MTD/RP2D. Once the MTD/RP2D is defined 
in Part E1, expansion cohorts of 40 subjects in selected tumor types will be enrolled as described in 
Part B to evaluate the antitumor activity of CX-2009 plus CX-072. A 2-stage design may be incorporated 
into this cohort.
Enrollment within the expansions will be suspended if either of the following Safety Stopping Rules are 
met in the first 6 subjects enrolled in Parts B, C2, D2, and E2:
x
DLT rate is >30% within 21 days (Parts B and E2) or within 28 days (Parts C2 and D2) of the first
dose of study drug
x
>20% of subjects have a treatment interruption or discontinuation within the first 6 weeks of the first 
dose of study drug or within 6 weeks of a single dose reduction step for subjects who experience 
events with their first dose of study drug
One of the major exploratory objectives aims at evaluating the relative Probody therapeutic activation in 
the tumor versus blood across various indications. The relative degree of Probody therapeutic activation 
in the tumor versus blood is expected to be influenced by Probody therapeutic dose, protease activity, and 
tumor target (CD166) expression. The variable nature of the protease activity and target expression in the 


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tumor between subjects is expected to lead to variation in relative Probody therapeutic activation. For 
Part A2, tumor biopsies are required 3 to 5 days after the first dose of CX-2009. For the dose expansion 
(Part B), consent to pretreatment and on-treatment tumor biopsies will be mandatory for at least 7 subjects 
for each tumor type.
Based on nonclinical data, the differential activation between tumor and blood has a mean of about 20.0% 
and a standard deviation of about 5.0%. For Part A2 with 6 subjects enrolled in a dose cohort, the 
90.0% CI (based on t-distribution with 5 degrees of freedom) for the differential activation is (16.0%, 
24.0%). For each of the expansion cohorts in Parts B and C2, the 90.0% CI (based on t-distribution with 
6 degrees of freedom) for the differential activation based on the best case scenario of 7 subjects is 
(16.3%, 23.7%), and based on the more likely scenario of 4 subjects is (14.1%, 25.9%). In addition, the 
variability in protease activity between subjects might further reduce our ability to measure Probody 
therapeutic activation in the tumor. It is anticipated that the requested tumor biopsies will provide 
reasonable estimates for this FIH study. If tumor biopsies are not mandatory, fewer subjects would be 
available for analysis, and the estimates would be less precise.
SITES
This is a multicenter study that will be conducted globally. Germany will participate only in Part B or C2 
of the study. UK will not participate in Parts D1, D2, E1, and E2 of the study. 
SPONSOR
CytomX Therapeutics, Inc.
151 Oyster Point Boulevard, Suite 400
South San Francisco, CA 94080-1913
USA
Telephone: +1-650-515-3185
Fax: +1-650-351-0353


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TABLE OF CONTENTS
SIGNATURE PAGE......................................................................................................................2 
INVESTIGATOR AGREEMENT ...............................................................................................3 
SYNOPSIS......................................................................................................................................4 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS.............................................30 
1 
INTRODUCTION AND BACKGROUND INFORMATION........................................34 
1.1 
CD166 (Activated Leukocyte Adhesion Molecule) in Human Cancer .............................34 
1.2 
Probody Therapeutics ........................................................................................................35 
1.3 
CX-2009 Overview............................................................................................................35 
1.3.1 
DM4 and DM4-Me Metabolism and Potential for Drug-Drug 
Interactions..........................................................................................................38 
1.3.2 
Nonclinical Toxicity Studies for CX-2009.........................................................38 
1.3.3 
CX-2009 Starting Dose for Escalation in Part A................................................39 
1.3.4 
Summary of CX-2009 Clinical Experience........................................................41 
1.4 
PD-1 and PD-L1 Inhibitors................................................................................................43 
1.5 
CX-072 Overview..............................................................................................................43 
1.5.1 
Summary of CX-072 Nonclinical Safety Data ...................................................44 
1.5.2 
Summary of CX-072 Clinical Experience..........................................................45 
1.6 
Rationale for the Combination of CX-2009 and CX-072..................................................46 
2 
STUDY OBJECTIVES.......................................................................................................48 
2.1 
Primary Objectives.............................................................................................................48 
2.1.1 
Part A – CX-2009 Monotherapy: Every 21-Day Dosing Regimen....................48 
2.1.2 
Part A2 – CX-2009 Monotherapy: Every 21-Day Dosing Regimen..................48 
2.1.3 
Part B – CX-2009 Monotherapy: Every 21-Day Dosing Regimen ....................48 
2.1.4 
Part C1 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen ..................49 
2.1.5 
Part C2 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen ..................49 
2.1.6 
Part D1 – CX-2009 + CX-072 Combination: Every 14-Day Dosing 
Regimen..............................................................................................................49 


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2.1.7 
Part D2 – CX-2009 + CX-072 Combination: Every 14-Day Dosing 
Regimen..............................................................................................................49 
2.1.8 
Part E1 – CX-2009 + CX-072 Combination: Every 21-Day Dosing 
Regimen..............................................................................................................49 
2.1.9 
Part E2 – CX-2009 + CX-072 Combination: Every 21-Day Dosing 
Regimen..............................................................................................................49 
2.2 
Secondary Objectives.........................................................................................................50 
2.2.1 
Part A – CX-2009 Monotherapy: Every 21-Day Dosing Regimen....................50 
2.2.2 
Part A2 – CX-2009 Monotherapy: Every 21-Day Dosing Regimen..................50 
2.2.3 
Part B – CX-2009 Monotherapy: Every 21-Day Dosing Regimen ....................51 
2.2.4 
Part C1 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen ..................51 
2.2.5 
Part C2 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen ..................52 
2.2.6 
Part D1 – CX-2009 + CX-072 Combination: Every 14-Day Dosing 
Regimen..............................................................................................................52 
2.2.7 
Part D2 – CX-2009 + CX-072 Combination: Every 14-Day Dosing 
Regimen..............................................................................................................53 
2.2.8 
Part E1 – CX-2009 + CX-072 Combination: Every 21-Day Dosing 
Regimen..............................................................................................................54 
2.2.9 
Part E2 – CX-2009 + CX-072 Combination: Every 21-Day Dosing 
Regimen..............................................................................................................54 
2.3 
Exploratory Objectives ......................................................................................................55 
2.3.1 
Part A – CX-2009 Monotherapy: Every 21-Day Dosing Regimen....................55 
2.3.2 
Part A2 – CX-2009 Monotherapy: Every 21-Day Dosing Regimen..................55 
2.3.3 
Part B – CX-2009 Monotherapy: Every 21-Day Dosing Regimen ....................56 
2.3.4 
Part C1 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen ..................56 
2.3.5 
Part C2 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen ..................56 
2.3.6 
Part D1 – CX-2009 + CX-072 Combination: Every 14-Day Dosing 
Regimen..............................................................................................................56 
2.3.7 
Part D2 – CX-2009 + CX-072 Combination: Every 14-Day Dosing 
Regimen..............................................................................................................57 
2.3.8 
Part E1 – CX-2009 + CX-072 Combination: Every 21-Day Dosing 
Regimen..............................................................................................................57 


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2.3.9 
Part E2 – CX-2009 + CX-072 Combination: Every 21-Day Dosing 
Regimen..............................................................................................................57 
3 
STUDY DESCRIPTION ....................................................................................................58 
3.1 
Summary of Study Design.................................................................................................58 
3.1.1 
Duration of Treatment, Follow-Up, and Study Completion...............................64 
3.2 
Part A (CX-2009 Monotherapy): Dose Escalation and Determination of 
MTD/RP2D for Every 21-Day Dosing Regimen (n d 79: Based on Actual 
Enrollment of Initial Cohorts and Assumption of Remaining Cohorts and Up 
to 38 Total Subjects Enrolled Into the Modified Toxicity Probability Interval-2
Design Cohort)...................................................................................................................65 
3.3 
Dose-Limiting Toxicity .....................................................................................................66 
3.4 
Part A2 (CX-2009 Monotherapy): Additional Enrollment Into Previously Cleared 
Dose Levels From Part A (n d 42) for Every 21-Day Dosing Regimen............................68 
3.5 
Part B (CX-2009 Monotherapy): Dose Expansion/Proof of Concept at 
MTD/RP2D for Every 21-Day Dosing Regimen With Proof of Concept in 
Selected Tumor Types (Maximum n d 200)......................................................................69 
3.6 
Part C1 (CX-2009 Monotherapy): Dose Escalation/De-escalation and 
Determination of MTD/RP2D for Every 14-Day Dosing Regimen (n d 24) ....................69 
3.7 
Part C2 (CX-2009 Monotherapy): Dose Expansion at the MTD/RP2D for Every 
14-Day Dosing Regimen in Selected Tumor Types (Maximum n d 200).........................70 
3.8 
Part D1 (CX-2009 + CX-072): Dose Escalation/De-escalation and Determination 
of MTD/RP2D for Every 14-Day Dosing Regimen in Selected Tumor Types 
(n d 24)...............................................................................................................................70 
3.9 
Part D2 (CX-2009 + CX-072): Dose Expansion for Every 14-Day Dosing 
Regimen in Selected Tumor Types (Maximum n d 200) ..................................................71 
3.10 
Part E1 (CX-2009 + CX-072): Dose Escalation and Determination of MTD/RP2D 
for Every 21-Day Dosing Regimen in Selected Tumor Types (n d 24)............................71 
3.11 
Part E2 (CX-2009 + CX-072): Dose Expansion for Every 21-Day Dosing 
Regimen in Selected Tumor Types (Maximum n d 200) ..................................................72 
4 
SELECTION AND WITHDRAWAL OF SUBJECTS ...................................................73 
4.1 
Inclusion Criteria ...............................................................................................................73 
4.2 
Exclusion Criteria ..............................................................................................................77 
4.3 
Additional Exclusion Criteria for Parts D1, D2, E1, and E2.............................................79 


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4.4 
Withdrawal Criteria ...........................................................................................................79 
5 
STUDY TREATMENTS....................................................................................................81 
5.1 
Treatment Groups ..............................................................................................................81 
5.2 
Rationale for Dosing..........................................................................................................81 
5.2.1 
CX-2009 as Monotherapy...................................................................................81 
5.2.2 
CX-2009 + CX-072 as Combination Therapy Every 14 Days, Dose 
Escalation/De-escalation (Part D1) and Expansion (Part D2)............................82 
5.2.3 
CX-2009 + CX-072 as Combination Therapy Every 21 Days, Dose 
Escalation (Part E1) and Expansion (Part E2)....................................................83 
5.3 
Randomization and Blinding .............................................................................................84 
5.4 
Breaking the Blind.............................................................................................................84 
5.5 
Drug Supplies and Administration.....................................................................................84 
5.5.1 
Formulation and Packaging ................................................................................84 
5.5.2 
Study Drug Preparation and Dispensing.............................................................84 
5.5.3 
Study Drug Administration.................................................................................84 
5.5.4 
Treatment Delays, Dose Modification, and Missed Doses.................................88 
5.5.5 
CX-072 Management of Immune-related Toxicity ............................................93 
5.5.6 
Adverse Event Recovery Monitoring .................................................................98 
5.5.7 
Treatment Compliance........................................................................................98 
5.5.8 
Storage and Accountability.................................................................................99 
5.5.9 
Discontinuation of CX-2009 for Adverse Events...............................................99 
5.5.10 
Discontinuation of CX-072 for Adverse Events...............................................100 
5.5.11 
Additional Guidelines.......................................................................................100 
5.6 
Prior and Concomitant Medications and/or Procedures ..................................................100 
5.6.1 
Excluded Medications and/or Procedures.........................................................100 
5.6.2 
Restricted Medications and/or Procedures........................................................101 
5.7 
Advice to Investigators Related to Potential Drug Interactions.......................................102 
6 
EFFICACY ASSESSMENTS ..........................................................................................102 


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7 
PHARMACOKINETIC, IMMUNOGENICITY, AND EXPLORATORY 
BIOMARKER ASSESSMENTS .....................................................................................103 
7.1 
Pharmacokinetic Assessments .........................................................................................103 
7.2 
Exploratory Biomarkers...................................................................................................103 
7.3 
Exploratory Biomarkers Collection.................................................................................104 
8 
SAFETY ASSESSMENTS...............................................................................................105 
8.1 
Adverse Events ................................................................................................................105 
8.1.1 
Suspected Adverse Reaction.............................................................................105 
8.1.2 
Life-Threatening Adverse Event or Life-Threatening Suspected Adverse 
Reaction ............................................................................................................105 
8.1.3 
Serious Adverse Event or Serious Suspected Adverse Reaction......................105 
8.1.4 
Unexpected Adverse Event or Unexpected Suspected Adverse Reaction........106 
8.2 
Adverse Event Classification...........................................................................................106 
8.2.1 
Relationship to Investigational Drug ................................................................106 
8.2.2 
Severity .............................................................................................................106 
8.3 
Exposure in Utero ............................................................................................................107 
8.4 
Monitoring of Adverse Event Data..................................................................................107 
8.5 
Documentation of Adverse Events by Investigator .........................................................108 
8.6 
Notification About Serious Adverse Events and Suspected Unexpected Serious 
Adverse Reactions ...........................................................................................................109 
8.6.1 
Investigator Reporting to Sponsor ....................................................................109 
8.6.2 
Serious Adverse Events Follow-Up..................................................................110 
8.6.3 
Reporting to Regulatory Agencies and Central Institutional Review 
Board/Independent Ethics Committees ............................................................110 
8.7 
Rapid Notification of Adverse Events of Special Interest...............................................111 
8.8 
Module-Specified Events.................................................................................................112 
9 
STATISTICAL CONSIDERATIONS ............................................................................113 
9.1 
Populations.......................................................................................................................115 
9.2 
Other Statistical Analyses................................................................................................115 


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10 
DATA SAFETY MONITORING BOARD ....................................................................115 
11 
INVESTIGATOR REQUIREMENTS AND QUALITY CONTROL.........................116 
11.1 
Ethical Conduct of the Study...........................................................................................116 
11.2 
Institutional Review Board or Independent Ethics Committee .......................................116 
11.3 
Subject Information and Informed Consent.....................................................................116 
11.4 
Retention of Records........................................................................................................117 
11.5 
Publication Policy............................................................................................................117 
11.6 
Financial and Insurance ...................................................................................................117 
12 
STUDY ADMINISTRATIVE INFORMATION ...........................................................118 
12.1 
Protocol Amendments......................................................................................................118 
12.2 
Address List .....................................................................................................................118 
12.2.1 
Sponsor .............................................................................................................118 
12.2.2 
Contract Research Organization .......................................................................118 
12.2.3 
Drug Safety.......................................................................................................118 
12.2.4 
Biological Specimens........................................................................................118 
13 
REFERENCES..................................................................................................................119 
LIST OF APPENDICES
Appendix A:   
Common Core Document CTMX-C-001 .......................................................122 
Appendix B:   
Schedule of Procedures...................................................................................123 
Appendix C:   
Synopsis of the mTPI-2 Design ......................................................................151 
Appendix D:   
Data Safety Monitoring Board........................................................................154 
Appendix E:   
Safety Review Committee ..............................................................................155 
Appendix F:   
Adjusted Ideal Body Weight Calculation .......................................................156 
Appendix G:   
List of Concomitant Medications Representing Inhibitors of CYP3A...........157 
Appendix H:   
List of Concomitant Medications Requiring Avoidance ................................158 
Appendix I:  
Description of Criteria to Assess CD166 Immunohistochemistry 
Staining ...........................................................................................................159 
Appendix J:   
Prior Lines of Therapy Counting Rule Guidance ...........................................160 


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LIST OF TABLES
Table 1.  
Prevalence of CD166 Expression in Human Cancers.......................................36 
Table 2.  
Human MTD for Disulfide Bond-DM4-containing ADCs...............................39 
Table 3.  
Neurotoxicity of CX-2009 and Other Maytansinoid ADCs in Monkeys .........41 
Table 4.  
Tumor Types and Enrollment by Part in Study CTMX-M-2009-001 ..............59 
Table 5.  
Dose-Limiting Toxicity.....................................................................................67 
Table 6.  
Monotherapy Dose Escalation Rules for 33 Design.......................................68 
Table 7.  
Management of Allergic Reactions...................................................................86 
Table 8.  
CX-2009 Dose Modifications for Select Adverse Events.................................89 
Table 9.  
Management of Treatment-emergent Ocular Disorders ...................................90 
Table 10.  
CX-072 Dose Modifications for Select Adverse Events...................................92 
Table 11.  
Adverse Event Severity...................................................................................107 
Table 12.   
Safety Contact Information: Medpace Clinical Safety ...................................109 
Table 13.  
Schedule of Procedures: Parts A, A2, and B...................................................124 
Table 14.  
Schedule of Procedures: Parts C1 and C2.......................................................128 
Table 15.  
Schedule of Procedures: Parts D1 and D2 ......................................................132 
Table 16.   
Schedule of Procedures: Parts E1 and E2 .......................................................136 
Table 17.  
Schedule of Vital Signs Measurements: All Parts ..........................................140 
Table 18.  
Schedule of PK and ADA Assessments: Parts A and A2...............................141 
Table 19.  
Schedule of PK and ADA Assessments: Part B..............................................142 
Table 20.  
Schedule of PK and ADA Assessments: Part C1............................................143 
Table 21.  
Schedule of PK and ADA Assessments: Parts C2..........................................144 
Table 22.  
Schedule of PK and ADA Assessments: Part D1 ...........................................145 
Table 23.  
Schedule of PK and ADA Assessments: Part D2 ...........................................147 
Table 24.   
Schedule of PK and ADA Assessments: Part E1............................................148 
Table 25.   
Schedule of PK and ADA Assessments: Part E2............................................150 
Table 26.  
List of Concomitant Medications Representing Inhibitors of CYP3A..........157 
Table 27.  
List of Concomitant Medications Requiring Avoidance ................................158 


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LIST OF FIGURES
Figure 1.   
CD166 Expression in CX-2009 Breast Cancer Sub-types................................36 
Figure 2.   
CD166 Expression in Breast Cancer Sub-types (TCGA) .................................37 
Figure 3.  
CX-2009 Enhances the Antitumor Activity of a Mouse Anti-PD-1
Probody Therapeutic in the CT26 HuCD166 Syngeneic Model ......................47 
Figure 4.   
Study Design Schema: Parts A, A2, and B (Every 21-Day Dosing 
Regimen)...........................................................................................................63 
Figure 5.  
Study Periods ....................................................................................................64 
Figure 6.  
Decision Table for mTPI-2 Cohort (Target Toxicity 
Probability = 30.0%).......................................................................................152 
Figure 7.  
Decision Table for mTPI-2 Cohort (Target Toxicity 
Probability = 20.0%).......................................................................................153 


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Page 1 of 4
a.m.
ante meridian, before noon
ACTH
adrenocorticotropic hormone
AD
acceptable dose
ADA
antidrug antibody
ADC
antibody-drug conjugate
ADL
activities of daily living
AE
adverse event
AIBW
adjusted ideal body weight
ALK
anaplastic lymphoma kinase
ALP
alkaline phosphatase
ALT
alanine aminotransferase 
aPTT
activated partial thromboplastin time
ASCO
American Society for Clinical Oncology
AST
aspartate aminotransferase
AUC
area under the concentration-time curve
BC
breast cancer
BRCA
BReast CAncer gene
BSA
body surface area
BUN
blood urea nitrogen
CA125
cancer antigen 125
CBC
complete blood count
CCC
cholangiocellular carcinoma
CDx
cluster of differentiation x
CFR
Code of Federal Regulations
CI
confidence interval
Cmax
maximal plasma concentration
Cmin
minimal plasma concentration
CMV
cytomegalovirus
CR
complete response
CRPC
castrate-resistant prostate carcinoma
CT
computed tomography
CTCAE
Common Terminology Criteria for Adverse Events
CV
cardiovascular
CYP
cytochrome P450
d
day
DAR
drug to antibody ratio
dL
deciliter
DLT
dose-limiting toxicity


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List of Abbreviations and Definitions of Terms 
Page 2 of 4
DM1
N2ƍ-deacetyl-N2ƍ-(3-mercapto-1-oxopropyl) maytansine
DM4
N2c-deacetyl-N2c-(4-mercapto-4-methyl-1-oxopentyl)-maytansine
DM4-Me
S-methyl DM4
DOR
duration of response
DOV
day of visit
DSMB
Data and Safety Monitoring Board
EC
endometrial carcinoma
ECG
electrocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
EDC
electronic data capture
EGFR
epidermal growth factor receptor
EOI
end of infusion
EOT
end of treatment
FDA
Food and Drug Administration
FIH
first in human
)5Į
folate receptor alpha
FSH
follicle-stimulating hormone
FT4
free thyroxine
g
gram
GI
gastrointestinal
GLP
Good Laboratory Practices
HCG
human chorionic gonadotropin
HER2
human epidermal growth factor receptor 2
HIV
human immunodeficiency virus
HNSCC
head and neck squamous cell carcinoma
HNSTD
highest nonseverely toxic dose
HR
hormone receptor
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use
ICI
immune checkpoint inhibitor
IEC
independent ethics committee
IgG1
immunoglobulin G subclass 1
IHC
immunohistochemistry
INR
international normalized ratio
irAE
immune-related adverse event
IRB
institutional review board
IRR
infusion-related reaction


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List of Abbreviations and Definitions of Terms 
Page 3 of 4
irRECIST
Immune-related Response Criteria in Solid Tumours
IV
intravenous(ly)
kg
kilogram
L
liter
LDH
lactate dehydrogenase
LH
luteinizing hormone
m2
square meter
mAb
monoclonal antibody
mg
milligram
mIU
milli-International Unit
mL
milliliter
mpk
milligram per kilogram
MRI
magnetic resonance imaging
MTD
maximum tolerated dose
mTPI-2
modified toxicity probability interval 2
MUC1
mucin 1
NA
not applicable
NCCN
National Comprehensive Cancer Network
NCI
National Cancer Institute
NE
not evaluated
nM
nanomolar
NOAEL
no observed adverse effect level
NSAID
nonsteroidal anti-inflammatory drug
NSCLC
non-small cell lung carcinoma
OEC
ovarian epithelial cancer
ORR
objective response rate
OS
overall survival
PAB
partial additive bag
PARP
polyadenosine diphosphate ribose
PD
pharmacodynamic(s)
PD-1
programmed death 1
PD-L1
programmed death ligand 1
PFS
progression-free survival
PK
pharmacokinetic(s)
PLT
platelet count
PO
per os, oral
POPPK
population pharmacokinetics
PR
partial response


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List of Abbreviations and Definitions of Terms 
Page 4 of 4
PSA
prostate-specific antigen
PT
prothrombin time
QSP
quantitative systems pharmacology
qxw
once every x weeks
RANK-L
receptor activator of nuclear factor kappa-B ligand
RECIST
Response Evaluation Criteria in Solid Tumours
RO
receptor occupancy
RP2D
recommended Phase 2 dose
SAE
serious adverse event
SD
stable disease
SGOT
serum glutamic oxaloacetic transaminase
SGPT
serum glutamic pyruvic transaminase
SPDB-DM4
N-succinimidyl 4-(2-pyridyldithio) butanoate-DM4
SRC
safety review committee
SUSAR
suspected unexpected serious adverse reaction
T-DM1
ado-trastuzumab emtansine
TEAE
treatment-emergent adverse event
TK
tyrosine kinase
TKI
tyrosine kinase inhibitor
TME
tumor microenvironment
TNBC
triple-negative breast cancer
71)Į
tumor necrosis factor alpha
TRAE
treatment-related adverse event
TSH
thyroid-stimulating hormone
TTR
time to tumor response
ULN
upper limit of normal
WFI
water for injection
g
microgram
L
microliter
m
micrometer
M
micromolar


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1
INTRODUCTION AND BACKGROUND INFORMATION 
This study is composed of 2 distinct documents:
•
A common core (“Core”; see separate synopsis [Appendix A]), and 
•
A CX-2009-specific module (“Module”; this document).
Briefly, the Core is a stable document that contains all the design features typically included in a 
standard Phase 1-2 protocol, but without reference to a specific experimental agent. The exact 
same core document is used for all Probody therapeutic first in human (FIH) studies, serving as a
centerpiece for all Probody therapeutics in development. It includes, for example, guidelines for
drug accountability, efficacy and safety parameters, and study administrative procedures. The 
CX-2009 Module (this current document), on the other hand, is customized for this specific 
Probody therapeutic, and all protocol guidelines necessary to safely manage subject care are 
included within the Module. Familiarity with both the Core and the CX-2009 Module is required 
for proper conduct of the study.
The Core plus Module system is a mechanism for bundling the clinical evaluation of Probody 
therapeutics within 1 unified program, with a common study design and common Investigator 
oversight. See the Core synopsis for a more detailed discussion of the Core design and rationale.
1.1
CD166 (Activated Leukocyte Adhesion Molecule) in Human Cancer
Antibody-drug conjugates (ADCs) are monoclonal antibodies (mAbs) that have been conjugated 
to cytotoxic small molecules through a linker. ADCs have shown their greatest clinical utility 
when targeting antigens expressed at very high levels on cancer cells. This is exemplified by the 
approvals of ado-trastuzumab emtansine (Kadcyla£) for human epidermal growth factor 
receptor 2 (HER2)-positive breast cancer (BC) and brentuximab vedotin (Adcetris£) for cluster 
of differentiation 30 (CD30)-positive Hodgkin disease and anaplastic large cell lymphoma. There 
are cell surface antigens that are highly expressed on cancer cells and therefore attractive for 
ADC targets, but may not have been progressed as ADC therapeutics because of concerns 
around their expression in normal tissues. One such target is CD166, also known as activated 
leukocyte cell adhesion molecule. CD166 is reported to be a cell adhesion molecule and to be
expressed on many cell types, including activated leukocytes, neurons, as well as epithelial and 
endothelial cells. CD166 has been reported to be a ligand for the CD6 receptor, which is 
expressed on T lymphocytes and implicated in T cell proliferation and activation (Weidle 2010).
However, the biological functions of CD166 are not well established.
CD166 shows homogenous high (3+) expression by immunohistochemistry (IHC) in most 
samples of multiple cancer types, but also is expressed in multiple normal tissues, including 
lung, gastrointestinal (GI) tract, and liver. Thus, CD166 has not previously been developed as a 
target for traditional ADCs.


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1.2
Probody Therapeutics
Trademark of CytomX Therapeutics, Inc. (Probody™) therapeutics are fully recombinant 
antibody prodrugs, activated preferentially by proteases present in tumor microenvironments
(TMEs). Because Probody therapeutics are designed to minimize interaction with targets outside 
of the TME, they potentially enable an ADC approach to effectively and safely target antigens 
such as CD166, which are expressed both in tumors and normal tissues. Nonclinical in vivo
studies show that Probody therapeutics remain substantially unable to bind its target in normal 
tissues and in circulation.
1.3
CX-2009 Overview
CytomX has developed an anti-human CD166 Probody therapeutic, termed CX-2009, selected 
for specific binding, internalization, and ability to elicit cytotoxicity. In addition, CX-2009
exhibits cross reactivity to cynomolgus monkeys, thus facilitating safety assessments in this 
species. CX-2009 is a humanized immunoglobulin G subclass 1 (IgG1) isotype N-succinimidyl 
4-(2-pyridyldithio) butanoate-N2c-deacetyl-N2c-(4-mercapto-4-methyl-1-oxopentyl)-maytansine 
(SPDB-DM4) drug conjugate and has been tested in nonclinical models for efficacy and safety. 
Treatment with CX-2009 at therapeutically relevant doses has led to significant tumor growth 
inhibition or regression in models of multiple tumor types including: lung, breast cancer (BC),
ovarian epithelial cancer (OEC), head and neck squamous cell carcinoma (HNSCC), and 
cholangiocellular carcinoma (CCC). These same doses were demonstrated to be well tolerated in 
cynomolgus monkeys. 
CD166 expression is particularly high in a number of cancers that are also sensitive to 
maytansinoid payloads or other microtubule inhibitors (MTIs) (National Comprehensive Cancer 
Network Guidelines). Maytansine, or its derivatives such as N2c-deacetyl-N2c-(4-mercapto-4-
methyl-1-oxopentyl)-maytansine (DM4), is a benzoansamacrolide and is considered to have a 
high affinity for tubulin located at the ends of microtubules. The suppression of microtubule 
dynamics causes cells to undergo cell cycle arrest, ultimately resulting in cell death via 
apoptosis. Two maytansine derivatives: emtansine, also referred to as N2c-deacetyl-N2c-
(3-mercapto-1-oxopropyl)-maytansine (DM1); and ravtansine, also referred to as SPDB-DM4, 
have been widely used in combination with irreversible and reversible linkers to generate ADCs 
(Bouchard 2014).
Frequently occurring cancer types also have high CD166 expression. These include breast, 
prostate, lung, ovarian, endometrial, head and neck, and biliary cancers, where prevalence of 
high CD166 expression (t2+ IHC) ranges from approximately 60.0% to greater than 90.0%
(Table 1). Thus, CX-2009 potentially represents a novel therapeutic approach, addressing a 
significant unmet medical need for a significant proportion of subjects across multiple cancer 
types.


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Table 1.
Prevalence of CD166 Expression in Human Cancers
Cancer Type
Prevalence of t2+IHC 
CD166 Expression
(IHC t2+) (%)
Prevalence of 
CD166-Negativity 
(IHC <1+) (%)
Number of Cases 
Examined (n)
Biliary
56.5
11.9
177
Breast
87.1
1.7
533
Endometrial
75.2
6.0
315
HNSCC
81.1
0.8
122
Lung
71.0
8.2
465
Ovarian
70.5
3.9
129
Prostate
98.3
0.8
119
CD166 = cluster of differentiation 166; HNSCC = head and neck squamous cell carcinoma; IHC = immunohistochemistry.
Source: CytomX Report RPT-NC-N-0025-00-01.
In the Sponsor’s analysis using the selected antibody for the IHC assay and tumor specimen data 
from the initial 39 BC subjects enrolled in this study in the central laboratory, it is estimated that 
greater than 90% of hormone receptor (HR)-positive/HER2-negative BC subjects will express 
CD166 and that approximately 50% of triple-negative breast cancer (TNBC) subjects will 
express CD166 (Figure 1). These data are replicated by using transcriptomic [messenger 
ribonucleic acid] assays based on 2 separate publicly available databases (METABRIC and The 
Cancer Genome Atlas [Figure 2]).
Figure 1.
CD166 Expression in CX-2009 Breast Cancer Sub-types 
CD166 = cluster of differentiation 166; Her2 = human epidermal growth factor receptor 2; HR = hormone receptor; 
TNBC = triple-negative breast cancer.


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Figure 2.
CD166 Expression in Breast Cancer Sub-types (TCGA)
CD166 = cluster of differentiation 166; ER = estrogen receptor; mRNA = messenger ribonucleic acid; PR = progesterone 
receptor; TCGA = The Cancer Genome Atlas; TNBC = triple negative breast cancer.
Subject selection in TNBC will help to eliminate subjects who have zero or low levels of CD166 
expression and are unlikely to respond to CX-2009.
CX-2009 is a Probody therapeutic derived from a proprietary, humanized anti-CD166 mAb, and 
conjugated to SPDB-DM4. CX-2009 has a drug to antibody ratio (DAR) of 3.5, similar to the
DARs observed in other DM4 ADCs in clinical use. Expression, purification, DM4 conjugation, 
formulation, characterization, stability, and administration of CX-2009 are similar to those for 
other mAbs.
The substrate of CX-2009 is designed to be cleaved by a number of proteases associated with
TMEs, including serine protease and matrix metalloproteinase classes (Overall 2006, 
LeBeau 2013). These proteases were chosen to activate CX-2009 because of their association 
with the human TME. In numerous cell line xenograft and patient-derived xenograft tumor 
models, treatment with CX-2009 has led to significant tumor growth inhibition or regression. It 
was also observed that, at the anticipated therapeutic dose levels, CX-2009 shows extended 
exposure in cynomolgus monkeys compared with the corresponding CD166-targeting ADC, 
consistent with CX-2009 avoidance of the antigen sink in normal tissues. Together, these results 


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indicate that CX-2009 can be efficiently activated in the tumor, while maintaining low binding to 
normal tissues. 
1.3.1
DM4 and DM4-Me Metabolism and Potential for Drug-Drug Interactions
In vitro studies evaluated the potential for involvement of human cytochrome P450 (CYP) 
isoforms in the metabolism of DM4 and S-methyl DM4 (DM4-Me). These studies identified 
CYP3A4 as the predominant CYP enzyme responsible for the oxidative metabolism of DM4 and 
DM4-Me in human hepatic microsomes. The biological significance of DM4 metabolism by 
CYP3A4 remains to be determined as the primary metabolite of DM4, DM4-Me, is not a product 
of oxidative metabolism but involves the methylation of DM4 by thiol S-methyltransferase
(Sun 2011). Cytochrome P450 3A4 may however play a primary role in the biotransformation of 
DM4-Me.
The potential for induction of specific CYP enzymes (CYP1A2, CYP2B6, and CYP3A4) by 
DM4 and DM4-Me was evaluated in cultured primary human hepatocytes. The results show no 
evidence for induction of CYP1A2, CYP2B6, and CYP3A4 in cultured human hepatocytes 
exposed to DM4 or DM4-Me. These data suggest that DM4-containing ADCs including 
CX-2009 will have a low likelihood of causing a drug-drug interaction mediated by induction of 
CYP isoforms.
1.3.2
Nonclinical Toxicity Studies for CX-2009
The toxicity of CX-2009 was evaluated in a Good Laboratory Practices (GLP)-compliant 21-day 
repeat-dose study in cynomolgus monkeys, where findings included injury to nerves (spinal cord 
and sciatic), hematologic tissues (bone marrow and lymphoid), and epithelial tissues (skin, 
tongue, and corneal). 
Hematologic findings consisted primarily of decreased cellularity in the bone marrow and lymph 
nodes; these findings were accompanied by hematology changes including moderate to marked 
decreases in neutrophils and were largely reversed following a 21-day recovery period. Myeloid 
toxicity is frequently observed with microtubule-targeted agents and was the primary toxicity 
noted in monkeys following administration of free DM4.
Epithelial findings noted in the skin, tongue, and cornea consisted of single-cell necrosis and 
increased mitoses, sometimes accompanied by inflammation or infiltrates, epidermal 
hyperplasia, and hyperkeratosis. In skin, these microscopic findings correlated with clinical 
observations of black, red, dry, swollen, or flaking skin. In the cornea, the findings correlated 
with ophthalmic observations of diffuse, very slight to moderate pigmentation of the epithelium,
and 1 case of blepharitis and ulcerative keratitis. The epithelial findings were reversed or in the 
process of reversing following a 21-day recovery period. Ocular toxicity has been a common
dose-limiting toxicity (DLT) for several DM4-ADCs (Younes 2012, Moore 2017).


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The CX-2009-related finding of axonal degeneration was present at all dose levels; while it was 
not reversed following a 21-day recovery period, the finding was of minimal or slight severity, 
did not result in measurable neurological impairment, and the lesion did not progress in severity 
over the duration of the study. Peripheral neuropathy is a well-described side effect of MTIs
(Dumontet 2010). While generally not dose limiting, peripheral neuropathy has been reported in 
clinical trials of Kadcyla (ado-trastuzumab emtansine or T-DM1) as well as most DM4-ADCs 
and is an expected toxicity for CX-2009 (Younes 2012, Diéras 2014, Moore 2017).
1.3.3
CX-2009 Starting Dose for Escalation in Part A
To avoid exposing subjects to unsafe levels of anticancer ADCs, but also minimize the number 
of subjects exposed to sub-efficacious dose levels, it has been suggested that the FIH starting 
dose for ADCs be at least 1 and fewer than 4 dose doublings below the expected maximum 
tolerated dose (MTD) (Saber 2015). The MTD for DM4-ADCs containing a cleavable disulfide 
linker (SPDB or sulfo-SPDB) and administered once every 3 weeks have been in a 4 mg/kg to 
6 mg/kg range (Table 2). CX-2009 is anticipated to have a MTD in the same range as other 
DM4-ADCs based on GLP toxicity study findings, which were similar to those reported for other 
maytansinoid ADCs and consistent with the activity of DM4. 
Based on the projected MTD of 4 mg/kg to 6 mg/kg, a CX-2009 starting dose of 0.25 mg/kg, 
which is 4 doublings below the lower end of the projected MTD range, is expected to be safe.
Table 2.
Human MTD for Disulfide Bond-DM4-containing ADCs
ADC
Target
Human MTD/RP2D/AD
Anetumab ravtansine 
(BAY 949343)
Mesothelin
6.5 mg/kg q3w
Note: half of subjects at MTD require dose reduction (Hassan 2015)
Coltuximab ravtansine 
(SAR3419)
CD19
160 mg/m2 (4.32 mg/kg) q3w (Younes 2012)
SAR566658,
huDS6-SPDB-DM4
CA6
190 mg/m² (5.14 mg/kg) q3w (Boni 2013)
IMGN242 (huC242-DM4)
MUC1
168 mg/m² (4.54 mg/kg) q3w (Goff 2009)
Indatuximab ravtansine 
(BT062)
CD138
160 mg/m2 (4.32 mg/kg) q3w
100 mg/m² (2.7 mg/kg) weekly x3 then 1 week off when combined 
with lenalidomide and low-dose dexamethasone (Zuber 2012, 
Kelly 2016)
Mirvetuximab 
soravtansine (IMGN853)
Folate 
receptor
6 mg/kg AIBW q3w (Borghaei 2015, Moore 2017)
AVE9633
CD33
150 mg/m2 (4.1 mg/kg) Days 1 and 8 every month 
(Lapusan 2012)
AD = acceptable dose; ADC = antibody-drug conjugate; AIBW = adjusted ideal body weight; CDx = cluster of differentiation x; 
DM4 = N2c-deacetyl-N2c-(4-mercapto-4-methyl-1-oxopentyl)-maytansine; MTD = maximum tolerated dose; MUC1 = mucin 1; 
q3w = every 3 weeks; RP2D = recommended Phase 2 dose; SPDB = N-succinimidyl 4-(2-pyridyldithio) butanoate.
Selection of the FIH starting dose based on the minimum anticipated biological effect level is not 
proposed as this would likely result in a starting dose that is approximately 10 dose doublings 


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below the anticipated MTD of CX-2009 and therefore inconsistent with the recommendations of 
Saber 2015. Additionally, the GLP toxicity study findings for CX-2009 are similar to those 
reported for other maytansinoid ADCs and are consistent with the effects of DM4.
Another approach to FIH starting dose selection for anticancer ADCs is to use 1/6 of the highest 
nonseverely toxic dose (HNSTD) in cynomolgus monkeys, scaled for body surface area (BSA). 
This formula has generally been found to result in an acceptable balance of safety and efficient 
dose escalation in Phase 1 trials of ADCs (Saber 2015). An HNSTD was not defined in the GLP 
toxicity study of CX-2009 due to histopathological findings of axonal degeneration, which did 
not reverse over a 3-week dose-free interval. There were no clinical observations consistent with 
functional neuropathy.
Peripheral neuropathy is a well-described side effect of MTIs (Dumontet 2010). While generally 
not dose limiting, peripheral neuropathy has been reported in clinical trials of Kadcyla as well as 
most DM4-ADCs and is an expected toxicity for CX-2009 (Diéras 2014, Moore 2017). 
Resolution rates of ADC-related peripheral neuropathy have ranged from ~19.0% to 54.0% upon 
treatment discontinuation (Stagg 2016).
In Table 3, CX-2009 is compared to 2 other maytansinoid ADCs, IMGN242 and Kadcyla, which 
also produced axonal degeneration in monkeys. The dose-dependent incidence and low severity 
of axonal injury associated with CX-2009 in monkeys appears generally similar to that of 
Kadcyla and IMGN242, which have been safely administered to cancer patients at starting doses 
of 0.3 mg/kg and 0.5 mg/kg, respectively.


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Table 3.
Neurotoxicity of CX-2009 and Other Maytansinoid ADCs in Monkeys
GLP Toxicity Study (Cynomolgus)
Clinical Starting Dose 
(mg/kg)
MTD (mg/kg)
DLT
Article 
(Schedule)
Dose Levels
(mg/kg)
Axonal Degeneration, 
Sciatic Nerve:
Incidence, Severity a
Axonal Degeneration,
Spinal Cord:
Incidence, Severity
CX-2009
(q3wu2)
C16-026
5
10
15
4/12, minimal to mild
8/12, minimal to mild
10/10, minimal to mild
5/12, minimal
11/12, minimal
10/10, minimal
IMGN242
(huC242-DM4)
(single dose)
CRT18-001
5 (NOAEL)
15 (HNSTD)
25
0/2
2/2, Grade 2
NE b
0/2
2/2, Grade 1
NE
5
4.54
Blurred vision
(Goff 2009)
Kadcyla
(T-DM1)
(q3wu4)
(Poon 2013)
3
10 (HNSTD)
30
0/14
6/14, minimal
14/14, slight to severe
0/14
8/14, minimal
14/14, slight to severe
0.3
3.6
Thrombocytopenia
(Krop 2010)
a Male and female combined; terminal and recovery animals combined.
b Not evaluated; animals did not survive to scheduled sacrifice on Day 29.
ADC = antibody-drug conjugate; DLT = dose-limiting toxicity; DM1 = N2ƍ-deacetyl-N2ƍ-(3-mercapto-1-oxopropyl) 
maytansine; DM4 = N2c-deacetyl-N2c-(4-mercapto-4-methyl-1-oxopentyl)-maytansine; GLP = Good Laboratory Practices;
HNSTD = highest nonseverely toxic dose; MTD = maximum tolerated dose; NE = not evaluated; NOAEL = no observed 
adverse effect level; q3wu2 = once every 3 weeks with a maximum of 2 doses; q3wu4 = once every 3 weeks with a maximum 
of 4 doses.
Axonal degeneration in CX-2009-treated animals was of minimal or mild severity, did not 
progress over the course of the study, and was not associated with clinical signs of neuropathy. 
Considering these factors, as well as the predictable and dose-dependent nature of this finding, 
and the monitorability of peripheral neuropathy in the clinic, an FIH starting dose of 0.25 mg/kg 
is considered to provide a reasonable safety factor while still allowing for efficient dose 
escalation in patients with advanced cancer. This dose is slightly below the human dose 
equivalent to 1/6 of the lowest dose tested in the GLP toxicity study (5 mg/kg) after scaling for 
BSA ([5 mg/kg ÷ 6] ÷ 3.1 = 0.27 mg/kg). No ocular toxicity was observed at the 5 mg/kg dose 
level in monkeys. A starting dose of 0.25 mg/kg is also 4 doublings below the lower end of the 
projected MTD range of 4 mg/kg to 6 mg/kg and is therefore consistent with published guidance 
as described above. An FIH starting dose of 0.25 mg/kg is therefore proposed for CX-2009.
1.3.4
Summary of CX-2009 Clinical Experience
Clinical data from Module CTMX-M-2009-001 as of a 30 November 2019 data lock point are 
summarized below.
Median duration of exposure to CX-2009 as of the data lock point was 7.3 weeks (maximum 
60 weeks).


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1.3.4.1
Summary of CX-2009 Clinical Safety
A total of 92 subjects treated with CX-2009 had available safety data. All but 6 subjects received 
CX-2009 once every 21 days at doses ranging from 0.25 mg/kg to 10 mg/kg. Six subjects 
received CX-2009 once every 14 days at a dose of 6 mg/kg. Please refer to the Investigator’s 
Brochure (IB) for the most up-to-date information.
Overview of Treatment-emergent Adverse Events
Approximately 91.3% (84 of 92) of subjects had adverse events (AEs) that were judged by the 
Investigator to be related to study treatment. Forty-two (45.7%) had ocular toxicity that was 
related to CX-2009, with symptoms similar to other DM4 ADCs. 
Twenty-six (28.3%) subjects experienced peripheral neuropathy related to CX-2009. The 
majority (13/26) had events that were Grade 1. Five subjects had Grade 3 peripheral neuropathy 
related to CX-2009.
Twenty (21.7%) subjects experienced infusion-related reactions (IRRs), the majority of which 
were Grade 1 or 2 (1 subject had a Grade 3 IRR). A previous analysis noted that the majority of 
subjects who had an IRR at the first infusion cycle, did not experience recurrence at subsequent 
infusions when premedication was administered.
Treatment-related SAEs and Treatment-related AEs Grade 3 or Higher 
Eleven (12.0%) subjects experienced treatment-related serious adverse events (SAEs). 
Thirty-four (37.0%) subjects experienced Grade 3/4 treatment-related adverse events (TRAEs), 
including 10 with ocular toxicity (n = 8 Grade 3, n = 2 Grade 4) and 5 with peripheral 
neuropathy (all Grade 3). 
There was 1 death related to study treatment according to Investigator’s assessment.
Refer to the most recent version of the CX-2009 IB for the most updated and complete safety 
data.
Dose-Limiting Toxicities
One DLT was observed in Part A (8 mg/kg every 21 days); a Grade 3 event of vomiting that 
resolved (22 subjects were treated at this dose and schedule). No DLTs were observed at 9 and 
10 mg/kg in 9 and 8 subjects, respectively.   
Three DLTs were reported in 2 out of 5 evaluable subjects who received CX-2009 at a dose of 
6 mg/kg every 14 days (Part C1) including a Grade 3 increased aspartate aminotransferase (AST)
and a Grade 3 increased alanine aminotransferase (ALT) in 1 subject, and a Grade 3 peripheral 
neuropathy in another subject.


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Treatment-emergent Adverse Events Related to CX-2009 at the Every 21-day 
Monotherapy RP2D of 7 mg/kg
As of 30 November 2019, treatment-emergent adverse events (TEAEs) related to CX-2009
reported in 2 or more subjects who received a dose of 7 mg/kg (n=9) administered every 21 days 
included nausea (44%), fatigue and infusion-related reactions (33% each), vomiting and 
arthralgia (22% each). Grade 3 TEAEs related to CX-2009 occurred in 2 subjects (1 subject with 
a Grade 3 peripheral neuropathy and a second subject reporting both Grade 3 nausea and Grade 3 
vomiting). No Grade 4 TEAEs related to CX-2009 or DLTs were reported at this dose level. 
Following a review of the safety and PK data, 7 mg/kg was determined as the monotherapy 
every 21-day RP2D (see Section 5.2).
1.3.4.2
Summary of CX-2009 Clinical Efficacy
As of 30 November 2019, 2 out of 92 (2.2%) response-evaluable subjects had a confirmed partial 
response (PR), 6 out of 92 (6.5%) had unconfirmed PRs, and 21 out of 92 (22.8%) achieved
stable disease ([SD]; at least 1 on-study scan with SD).
1.4
PD-1 and PD-L1 Inhibitors
The immune system has recently emerged as a highly promising target for the treatment of 
cancer. T cells are capable of recognizing many cancers as foreign, and, when optimally 
mobilized, can induce potent and durable responses in patients against many cancer types. 
However, tumors can evade immunity by exploiting the same mechanisms that in healthy tissue 
serve to regulate immune function. One such mechanism is through expression of programmed 
death ligand 1 (PD-L1), a ligand that negatively regulates T cell activity through its interaction 
with programmed death 1 (PD-1), an inhibitory receptor expressed on activated T cells. The 
normal role of PD-L1 is to minimize immune-mediated damage to tissues under conditions of 
chronic T cell stimulation or from attack by autoreactive T cells. Expression of PD-L1 is 
dynamic and induced most potently by interferon gamma produced by activated T cells, and it 
functions in a negative feedback loop to suppress the activity of T cells involved in a local tissue 
attack. PD-L1 is now understood to be a dominant means by which tumors can evade the 
immune system. Clinical trials have confirmed the capacity of PD-1/PD-L1 blockade to restore 
tumor specific immunity and improve outcomes for patients with cancer, leading to regulatory 
approvals to treat a number of tumor types (Balar 2017).
1.5
CX-072 Overview
CX-072 is a Probody therapeutic directed against PD-L1 for the treatment of cancer and is the 
first under the CytomX Probody platform to be studied in humans. CX-072 is designed to widen 
the therapeutic window by reducing interaction with PD-L1 in normal tissue environments while 
maintaining interaction with tumor tissue. 


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CX-072 is a Probody therapeutic derived from a proprietary human anti–PD-L1 mAb. In patients 
with various cancers, anti–PD-L1 mAb (atezolizumab, avelumab, and durvalumab) and 
anti-PD-1 mAb (nivolumab, pembrolizumab, and cemiplimab) have demonstrated clinical safety 
and effectiveness as monotherapy and/or in combination with other immunotherapies
(LaFleur 2018). However, significant life-threatening toxicities have been observed with these 
agents, particularly in combination regimens. The most common SAEs that lead to premature 
discontinuation of therapy or death are immune-related and are most likely attributable to 
drug-induced inflammation outside of the tumor (Larkin 2015). CX-072 is intended to provide 
antitumor efficacy similar to that of other PD-L1 and PD-1 inhibitors, but with an improved 
safety profile, especially when given in combination with other therapeutics. 
Expression, purification, formulation, characterization, quality attributes, stability, and 
administration of CX-072 are similar to that of other mAbs.
CX-072 is designed to be activated by a number of proteases associated with the TME, including 
serine proteases and matrix metalloproteinases classes. These proteases were chosen because 
there is published evidence that they are activated in human tumors (Overall 2006, 
LeBeau 2013), and generally, they have low activity in blood or in select normal tissues.
1.5.1
Summary of CX-072 Nonclinical Safety Data
GLP-compliant 4-week repeat-dose general toxicity studies of CX-072 were conducted in rats 
and cynomolgus monkeys. These studies evaluated dose levels of 20, 60, and 200 mg/kg 
administered once weekly over 28 days (5 doses) by IV infusion, followed by a 4-week postdose 
recovery. 
CX-072 was well tolerated by rats and monkeys in the GLP toxicity studies, with no significant 
effect on clinical signs, body weights, clinical pathology, ophthalmology, or safety 
pharmacology endpoints. No toxicologically significant effects on immune function were noted 
with CX-072 treatment as assessed by peripheral blood immunophenotyping and plasma 
cytokine analyses. A single mortality in one 200 mg/kg/dose female monkey that occurred soon 
after the third dose was considered possibly procedure-related.
In the rat GLP-compliant study, CX-072–related microscopic findings included liver Kupffer cell 
hypertrophy, pancreatic acinar cell atrophy, and pancreatic mononuclear cell inflammation. 
Changes in the pancreas persisted in recovery animals. An additional finding in recovery animals 
was mononuclear cell inflammation of the thyroid. The inflammatory changes in the pancreas 
and thyroid are suggestive of immune checkpoint inhibition and, as such, are consistent with the 
anticipated pharmacological effects of CX-072. The marked severity and persistent nature of the 
thyroid and pancreas findings in some mid-dose and high-dose animals was considered 
potentially adverse, therefore the no observed adverse effect level (NOAEL) was 20 mg/kg.
In the monkey GLP study, CX-072 was associated with microscopic findings of perivascular 
inflammation, primarily in the gallbladder, heart, aorta, pancreas, and multiple levels of the GI 


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tract. This pattern of inflammation is characteristic of biotherapeutic induced vasculitis in animal 
species, a finding that is often attributed to immunogenicity but may also be a direct 
pharmacological effect of ICIs such as CX-072 (Frazier 2015). While adverse, these changes 
were not observed in recovery animals and were therefore reversible. Based on these findings, 
the NOAEL was 60 mg/kg/dose for females and could not be determined for males. The HNSTD 
in male and female monkeys was 200 mg/kg.
Additional information may be found in the CX-072 IB.
1.5.2
Summary of CX-072 Clinical Experience
Study CTMX-M-072-001, an FIH, Phase 1-2a study is currently ongoing and is composed of 
7 parts: Part A – monotherapy dose escalation; Part A2 – biomarker assessment and dose effect;
Parts B1 and B2 – combination with ipilimumab; Part C – combination with vemurafenib; and 
Parts D and E – monotherapy treatment expansion in select tumor types.
Enrollment in the dose escalation phase of Part A (the Phase 1 monotherapy portion of the study; 
CX-072 doses up to 30 mg/kg) has been completed without reaching the MTD. The 
recommended Phase 2 dose (RP2D) was determined to be 10 mg/kg CX-072 once every 14 days, 
which is equivalent to the 800 mg every 14 days fixed dose. 
Clinical data from Parts A, A2, and D (monotherapy) are summarized below.
1.5.2.1
Summary of CX-072 Clinical Safety 
Overview of Treatment-emergent Adverse Events
As of 30 November 2019, 111 out of 114 (approximately 97%) subjects who received CX-072
monotherapy at the 10 mg/kg dose level experienced a TEAE, 61 (53.5%) subjects experienced a 
TEAE Grade 3, and 3 (2.6%) subjects experienced an immune-related adverse event (irAE) 
Grade 3.
Twelve out of 114 (approximately 11%) subjects who received CX-072 monotherapy at the 
10 mg/kg dose level experienced IRRs, all RIZKLFKZHUH*UDGH
Treatment-related SAEs and Treatment-related AEs Grade 3 or Higher 
Of 114 subjects who received CX-072 monotherapy at the 10 mg/kg dose level, 
6 (5.3%) subjects had treatment-related SAEs, and 12 (10.5%) subjects KDG75$(V*UDGH
There were no treatment-related deaths reported according to Investigator’s assessment.
Refer to the most recent version of the CX-072 IB for the most recent and complete safety data.


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1.5.2.2
Summary of CX-072 Clinical Efficacy
As of 30 November 2019, in the 114 efficacy-evaluable subjects who received 10 mg/kg CX-072
as monotherapy in Parts A, A2, and D, 12 (10.5%) subjects achieved a PR (10 confirmed, 
2 unconfirmed) and 37 (32.5%) subjects achieved SD. The disease control rate was 43.0%.
1.6
Rationale for the Combination of CX-2009 and CX-072
Immune checkpoint inhibitors (ICIs) have been shown to induce potent and durable antitumor
immunity in many cancer types. Nevertheless, a minority of patients benefit from single-agent 
immunotherapy (Du 2017; Jacquelot 2017). Combination of ICIs with conventional 
chemotherapy has been evaluated for that reason in various indications and led to several 
approvals (KEYNOTE 189 Gandhi 2018; Impower 133 Horn 2018; Impassion 130 
Schmid 2018; and Impower 150 Socinski 2018). Combinations with conventional chemotherapy 
come with the liability of chemotherapy-related toxicities. A more targeted approach with an 
ADC may offer means to mitigate part of this toxicity. Data summarized below suggest that 
combining ICIs with ADC or Probody drug conjugate therapeutics may provide enhanced 
antitumor activity compared to monotherapy. It has been demonstrated that ADCs are not only 
capable of killing cancer cells but also can modulate the immune response. Cytotoxic 
payload/ADCs have been shown to induce immunogenic cell death in vitro and in vivo 
(Rios-Doria 2017). Immunologic cell death is described as the release of danger signals or 
damage-associated molecular patterns that elevate the immunogenic potential of dying cells 
(Garg 2015). In addition to elevating the immunogenic potential of cancer cells, cytotoxic 
payloads can also provoke phenotypic and functional dendritic cell maturation and activation 
(Müller 2014). Thus, it appears that cytotoxic payloads not only have cytotoxic effects, but may 
also potentiate an immune response through multiples modalities. These observations provide a 
mechanistic rationale for the combination of ADCs and ICIs.
These concepts have been translated in published nonclinical studies where the combination of 
ADCs bearing various payloads synergized with immunotherapies (Müller 2015, 
Rios-Doria 2017). Müller et al also reported that T cells are recruited in the TME upon T-DM1 
therapy in human and murine BCs (Müller 2015). 
The activity of CX-2009 in combination with an effector-null surrogate Probody therapeutic to 
mouse PD-1 was investigated in a subcutaneous mouse cell line cancer model (Liu 2019 and data 
on file). As both anti–PD-1 and anti–PD-L1 block signaling in this pathway which results in 
inhibition of T cell responses, the use of anti–PD-1 Probody therapeutic was considered 
sufficient to address the impact of pathway blockade in these combination studies. The syngeneic 
CT26 mouse colon cancer cell line was transfected with human CD166 (CT26-hCD166), the 
target for CX-2009, to render the cell line sensitive to CX-2009 activity. BALB/c mice were 
implanted subcutaneously with CT26-hCD166, and tumors allowed to establish prior to the 
initiation of CX-2009 and anti–PD-1 Probody therapeutic dosing. Neither CX-2009 nor 


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anti-PD-1 Probody therapeutic monotherapy result in regressions in mice with established 
CT26-hCD166 tumors (Figure 3); however, the combination produced tumor regressions in 51% 
of mice (highlighted in red). These results suggest that a Probody therapeutic to the PD-1
pathway combined with CX-2009 can synergize to improve antitumor activity in this nonclinical 
model.
Figure 3.
CX-2009 Enhances the Antitumor Activity of a Mouse Anti-PD-1
Probody Therapeutic in the CT26 HuCD166 Syngeneic Model
Notes: Red graph lines indicate the combination of CX-2009 + PD-1 Pb-Tx produced tumor regressions in 51% of mice.
huCD166 = human cluster of differentiation 166; Pb-Tx = Probody therapeutic; PBS = phosphate-buffered saline; 
PD-1 = programmed death 1.
Source: data on file.
Data are available from 2 clinical studies of maytansinoid-based ADCs in combination with ICIs
which support the benefit of these combinations in patients. In the Phase 1b FORWARD II 
study, mirvetuximab soravtansine, a folate receptor alpha (FRĮ)-targeting ADC, was combined 
with pembrolizumab in platinum-resistant ovarian cancer patients. The confirmed objective 
response rate (ORR) suggests a trend toward clinical benefit (Matulonis 2018). 
The KATE2 trial was a randomized Phase 2 study of atezolizumab combined with trastuzumab 
emtansine (T-DM1) versus placebo combined with T-DM1 in previously treated HER2-positive 
advanced BC patients. In the PD-L1+ subgroups, the combination of T-DM1 + atezolizumab 
R E G :  5 1 %
R E G :  0 %
R E G :  0 %
R E G :  0 %


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resulted in a 54% ORR while the T-DM1 + placebo arm had a 33% ORR (Emens 2018). In the 
PD-L1+ subgroups, progression-free survival (PFS) was extended from 4.1 months in the 
T-DM1 + placebo group to 8.5 months in the T-DM1 + atezolizumab group (stratified hazard 
ratio, 0.60). These data indicate a potential durable clinical benefit for combination of 
an anti-PD-L1 antibody and a maytansinoid ADC in a PD-L1+ patient population.
In this module, CX-2009 will be combined with CX-072 investigating 2 schedules (every 
14 days and every 21 days). Given the safety profile of CX-072, the starting dose for CX-072
will be fixed at 800 and 1200 mg for these 2 schedules, respectively. The starting dose for 
CX-2009 for these 2 schedules (every 14 days and every 21 days) will be set at the every 14-day
monotherapy RP2D as determined in Part C1 and at 7 mg/kg every 21 days (the every 21-day 
RP2D as previously determined in Part A/A2), respectively. Lower starting doses may be used 
based on emerging safety data and in consultation with the SRC.
2
STUDY OBJECTIVES
2.1
Primary Objectives
2.1.1
Part A – CX-2009 Monotherapy: Every 21-Day Dosing Regimen
The primary objective of Part A is to determine the safety profile of CX-2009, the MTD/RP2D, 
and the DLTs of CX-2009 when administered intravenously (IV) every 21 days as monotherapy 
to subjects with selected advanced or recurrent solid tumors.
2.1.2
Part A2 – CX-2009 Monotherapy: Every 21-Day Dosing Regimen
The primary objectives of Part A2 are to determine the following in subjects treated with CX-2009
every 21 days:
•
Characterize the protease activity and measure the cleavage of CX-2009 in tumor biopsies 
and peripheral blood; and
•
Obtain additional characterization of the safety of CX-2009 when administered as 
monotherapy at dose levels evaluated in Part A.
2.1.3
Part B – CX-2009 Monotherapy: Every 21-Day Dosing Regimen
The primary objective of Part B is to evaluate the efficacy of CX-2009 when administered IV 
every 21 days as monotherapy at the MTD/RP2D (as defined in consideration of available data 
from Part A and Part A2) in subjects with selected advanced or recurrent solid tumors. Efficacy 
will be assessed on the basis of the ORR by the Response Evaluation Criteria in Solid Tumours 
(RECIST) Version 1.1.


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2.1.4
Part C1 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen
The primary objective of Part C1 is to determine the safety profile of CX-2009, the MTD/RP2D, 
and the DLTs of CX-2009 when administered IV every 14 days as monotherapy to subjects with 
selected advanced or recurrent solid tumors.
2.1.5
Part C2 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen
The primary objective of Part C2 is to evaluate the efficacy of CX-2009 when administered IV 
every 14 days as monotherapy at the MTD/RP2D to subjects with selected advanced or recurrent 
solid tumors. Efficacy will be assessed on the basis of the ORR by the RECIST Version 1.1.
2.1.6
Part D1 – CX-2009 + CX-072 Combination: Every 14-Day Dosing Regimen
The primary objective of Part D1 is to determine the safety profile, the MTD/RP2D, and the 
DLTs of CX-2009 in combination with CX-072, both administered IV every 14 days to subjects 
with selected advanced or recurrent solid tumors.
2.1.7
Part D2 – CX-2009 + CX-072 Combination: Every 14-Day Dosing Regimen
The primary objective of Part D2 is to evaluate the efficacy of CX-2009 in combination with 
CX-072, both administered IV every 14 days at the MTD/RP2D to subjects with selected 
advanced or recurrent solid tumors. Efficacy will be assessed on the basis of ORR per RECIST 
Version 1.1.
2.1.8
Part E1 – CX-2009 + CX-072 Combination: Every 21-Day Dosing Regimen
The primary objective of Part E1 is to determine the safety profile, the MTD/RP2D, and the 
DLTs of CX-2009 in combination with CX-072, both administered IV every 21 days to subjects 
with selected advanced or recurrent solid tumors.
2.1.9
Part E2 – CX-2009 + CX-072 Combination: Every 21-Day Dosing Regimen
The primary objective of Part E2 is to evaluate the efficacy of CX-2009 in combination with 
CX-072, both administered IV every 21 days at the MTD/RP2D to subjects with selected 
advanced or recurrent solid tumors. Efficacy will be assessed on the basis of ORR per RECIST 
Version 1.1.


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2.2
Secondary Objectives
2.2.1
Part A – CX-2009 Monotherapy: Every 21-Day Dosing Regimen
The secondary objectives of Part A are to determine the following in subjects treated with 
CX-2009 every 21 days:
•
Evaluate preliminary efficacy in subjects treated with CX-2009 as monotherapy on the basis 
of:
–
ORR by the RECIST Version 1.1;
–
Time to tumor response (TTR);
–
Duration of response (DOR);
–
PFS; and
–
Overall survival (OS);
•
Characterize the pharmacokinetics (PK) of CX-2009 with respect to the following analytes:
–
Intact CX-2009 (referring to the prodrug form of CX-2009 r DM4);
–
Total CX-2009 (intact and activated forms of CX-2009 r DM4);
–
Total CX-2009-conjugated DM4 (antibody conjugated-DM4);
–
Free DM4; and
–
DM4-Me - a DM4 metabolite with potent cytotoxic activity; and 
•
Assess the incidence of antidrug antibody (ADA) formation to CX-2009.
2.2.2
Part A2 – CX-2009 Monotherapy: Every 21-Day Dosing Regimen
The secondary objectives of Part A2 are to determine the following in subjects treated with 
CX-2009 every 21 days:
•
Evaluate preliminary efficacy in subjects treated with CX-2009 as monotherapy on the basis 
of:
–
ORR by the RECIST Version 1.1;
–
TTR;
–
DOR;
–
PFS; and
–
OS;
•
Characterize the PK of CX-2009 with respect to the following analytes:
–
Intact CX-2009 (referring to the prodrug form of CX-2009 r DM4);
–
Total CX-2009 (intact and activated forms of CX-2009 r DM4);
–
Total CX-2009-conjugated DM4 (antibody conjugated-DM4);


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–
Free DM4; and
–
DM4-Me; and
•
Assess the incidence of ADA formation to CX-2009.
2.2.3
Part B – CX-2009 Monotherapy: Every 21-Day Dosing Regimen
The secondary objectives of Part B are to determine the following in subjects treated with 
CX-2009 every 21 days:
•
Obtain additional characterization of the safety of CX-2009 at the MTD/RP2D;
•
Evaluate efficacy in subjects treated with CX-2009 as monotherapy on the basis of:
–
DOR;
–
TTR;
–
PFS; and
–
OS;
•
Characterize the PK of CX-2009 with respect to the following analytes:
–
Intact CX-2009 (referring to the prodrug form of CX-2009 r DM4);
–
Total CX-2009 (intact and activated forms of CX-2009 r DM4);
–
Total CX-2009-conjugated DM4 (antibody conjugated-DM4);
–
Free DM4; and
–
DM4-Me; and
•
Assess the incidence of ADA formation to CX-2009.
2.2.4
Part C1 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen
The secondary objectives of Part C1 are to determine the following in subjects treated with 
CX-2009 every 14 days:
•
Evaluate preliminary efficacy in subjects treated with CX-2009 as monotherapy on the basis 
of:
–
ORR by the RECIST Version 1.1;
–
TTR;
–
DOR;
–
PFS; and
–
OS;
•
Characterize the PK of CX-2009 with respect to the following analytes:
–
Intact CX-2009 (referring to the prodrug form of CX-2009 r DM4);
–
Total CX-2009 (intact and activated forms of CX-2009 r DM4);
–
Total CX-2009-conjugated DM4 (antibody conjugated-DM4);


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–
Free DM4; and
–
DM4-Me; and
•
Assess the incidence of ADA formation to CX-2009.
2.2.5
Part C2 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen
The secondary objectives of Part C2 are to determine the following in subjects treated with 
CX-2009 every 14 days:
•
Obtain additional characterization of the safety of CX-2009 at the MTD/RP2D;
•
Evaluate efficacy in subjects treated with CX-2009 as monotherapy on the basis of:
–
DOR;
–
TTR;
–
PFS; and
–
OS;
•
Characterize the PK of CX-2009 with respect to the following analytes:
–
Intact CX-2009 (referring to the prodrug form of CX-2009 r DM4);
–
Total CX-2009 (intact and activated forms of CX-2009 r DM4);
–
Total CX-2009-conjugated DM4 (antibody conjugated-DM4);
–
Free DM4; and
–
DM4-Me; and
•
Assess the incidence of ADA formation to CX-2009.
2.2.6
Part D1 – CX-2009 + CX-072 Combination: Every 14-Day Dosing Regimen
The secondary objectives of Part D1 are to determine the following in subjects treated with 
CX-2009 plus CX-072 every 14 days:
•
Evaluate preliminary efficacy in subjects treated with CX-2009 plus CX-072 on the basis of:
–
ORR by the RECIST Version 1.1;
–
ORR by immune-related RECIST (irRECIST) as defined in the Core;
–
TTR;
–
DOR;
–
PFS; and
–
OS;
•
Characterize the PK of CX-2009 when it is administered in combination with CX-072 with 
respect to the following analytes:
–
Intact CX-2009 (referring to the prodrug form of CX-2009 r DM4);
–
Total CX-2009 (intact and activated forms of CX-2009 r DM4);
–
Total CX-2009-conjugated DM4 (antibody conjugated-DM4);


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–
Free DM4; and
–
DM4-Me; 
•
Assess the incidence of ADA formation to CX-2009 when it is administered in combination 
with CX-072;
•
Characterize the PK profile of CX-072 when it is administered in combination with 
CX-2009; and 
•
Assess the incidence of ADA formation to CX-072 when it is administered in combination 
with CX-2009.
2.2.7
Part D2 – CX-2009 + CX-072 Combination: Every 14-Day Dosing Regimen
The secondary objectives of Part D2 are to determine the following in subjects treated with 
CX-2009 plus CX-072 every 14 days:
•
Obtain additional characterization of the safety of CX-2009 administered with CX-072 at the 
MTD/RP2D;
•
Evaluate efficacy in subjects treated with CX-2009 plus CX-072 on the basis of:
–
DOR;
–
TTR;
–
PFS;
–
OS; and
–
ORR by irRECIST as defined in the Core; 
•
Characterize the PK of CX-2009 when it is administered in combination with CX-072 with 
respect to the following analytes:
–
Intact CX-2009 (referring to the prodrug form of CX-2009 r DM4);
–
Total CX-2009 (intact and activated forms of CX-2009 r DM4);
–
Total CX-2009-conjugated DM4 (antibody conjugated-DM4);
–
Free DM4; and
–
DM4-Me; 
•
Assess the incidence of ADA formation to CX-2009 when it is administered in combination 
with CX-072;
•
Characterize the PK profile of CX-072 when it is administered in combination with 
CX-2009; and
•
Assess the incidence of ADA formation to CX-072 when it is administered in combination 
with CX-2009.


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2.2.8
Part E1 – CX-2009 + CX-072 Combination: Every 21-Day Dosing Regimen
The secondary objectives of Part E1 are to determine the following in subjects treated with 
CX-2009 plus CX-072 every 21 days:
•
Evaluate preliminary efficacy in subjects treated with CX-2009 plus CX-072 on the basis of:
–
ORR by the RECIST Version 1.1;
–
ORR by irRECIST as defined in the Core;
–
TTR;
–
DOR;
–
PFS; and
–
OS;
•
Characterize the PK of CX-2009 when it is administered in combination with CX-072 with 
respect to the following analytes:
–
Intact CX-2009 (referring to the prodrug form of CX-2009 r DM4);
–
Total CX-2009 (intact and activated forms of CX-2009 r DM4);
–
Total CX-2009-conjugated DM4 (antibody conjugated-DM4);
–
Free DM4; and
–
DM4-Me; 
•
Assess the incidence of ADA formation to CX-2009 when it is administered in combination 
with CX-072;
•
Characterize the PK profile of CX-072 when it is administered in combination with 
CX-2009; and 
•
Assess the incidence of ADA formation to CX-072 when it is administered in combination 
with CX-2009.
2.2.9
Part E2 – CX-2009 + CX-072 Combination: Every 21-Day Dosing Regimen
The secondary objectives of Part E2 are to determine the following in subjects treated with 
CX-2009 plus CX-072 every 21 days:
•
Obtain additional characterization of the safety of CX-2009 administered with CX-072 at the 
MTD/RP2D;
•
Evaluate efficacy in subjects treated with CX-2009 plus CX-072 on the basis of:
–
DOR;
–
TTR;
–
PFS;
–
OS; and
–
ORR by irRECIST as defined in the Core; 


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•
Characterize the PK of CX-2009 when it is administered in combination with CX-072 with 
respect to the following analytes:
–
Intact CX-2009 (referring to the prodrug form of CX-2009 r DM4);
–
Total CX-2009 (intact and activated forms of CX-2009 r DM4);
–
Total CX-2009-conjugated DM4 (antibody conjugated-DM4);
–
Free DM4; and
–
DM4-Me; 
•
Assess the incidence of ADA formation to CX-2009 when it is administered in combination 
with CX-072;
•
Characterize the PK profile of CX-072 when it is administered in combination with 
CX-2009; and
•
Assess the incidence of ADA formation to CX-072 when it is administered in combination 
with CX-2009.
2.3
Exploratory Objectives
2.3.1
Part A – CX-2009 Monotherapy: Every 21-Day Dosing Regimen
The exploratory objectives of Part A are to determine the following in subjects treated with 
CX-2009 every 21 days:
•
Explore potential predictive markers associated with CX-2009 clinical activity such as
CD166 expression in tumor specimens prior to and while receiving treatment; and
•
Characterize the protease activity in optional pretreatment tumor biopsies and activation of 
CX-2009 in optional on-treatment tumor biopsies and peripheral blood.
2.3.2
Part A2 – CX-2009 Monotherapy: Every 21-Day Dosing Regimen
The exploratory objectives of Part A2 are to determine the following in subjects treated with 
CX-2009 every 21 days:
•
Evaluate the relationship between CX-2009 dose and exposure, exploratory biomarkers, 
safety, and efficacy of CX-2009 as monotherapy in subjects with selected advanced or 
recurrent solid tumors; and
•
Explore potential predictive markers associated with CX-2009 clinical activity such as 
CD166 expression in tumor specimens while receiving treatment.


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2.3.3
Part B – CX-2009 Monotherapy: Every 21-Day Dosing Regimen
The exploratory objectives of Part B are to determine the following in subjects treated with 
CX-2009 every 21 days:
•
Explore potential predictive markers associated with CX-2009 clinical activity such as 
CD166 expression in tumor specimens prior to and while receiving treatment;
•
Measure the intact and activated CX-2009 in on-treatment tumor biopsies and peripheral 
blood; and
•
Characterize the protease activity in pretreatment tumor biopsies.
2.3.4
Part C1 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen
The exploratory objectives of Part C1 are to determine the following in subjects treated with 
CX-2009 every 14 days:
•
Explore potential predictive markers associated with CX-2009 clinical activity such as 
CD166 expression in tumor specimens prior to and while receiving treatment; and
•
Characterize the protease activity in optional pretreatment tumor biopsies and activation of 
CX-2009 in optional on-treatment tumor biopsies and peripheral blood.
2.3.5
Part C2 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen
The exploratory objectives of Part C2 are to determine the following in subjects treated with 
CX-2009 every 14 days:
•
Explore potential predictive markers associated with CX-2009 clinical activity such as 
CD166 expression in tumor specimens prior to and while receiving treatment; and
•
Characterize the activation of CX-2009 in on-treatment tumor biopsies and peripheral blood.
2.3.6
Part D1 – CX-2009 + CX-072 Combination: Every 14-Day Dosing Regimen
The exploratory objectives of Part D1 are to determine the following in subjects treated with 
CX-2009 plus CX-072 every 14 days:
•
Explore potential predictive markers associated with clinical activity of the treatment 
combination such as CD166 expression and PD-L1 status in tumor specimens prior to and 
while receiving treatment;
•
Characterize the protease activity and the activation of CX-2009 and CX-072 in optional 
on-treatment tumor biopsies and peripheral blood; and
•
Investigate the immunomodulatory activity of the treatment combination in optional 
on-treatment tumor biopsies (fixed and frozen).


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2.3.7
Part D2 – CX-2009 + CX-072 Combination: Every 14-Day Dosing Regimen
The exploratory objectives of Part D2 are to determine the following in subjects treated with 
CX-2009 plus CX-072 every 14 days:
•
Explore potential predictive markers associated with clinical activity of the treatment 
combination such as CD166 expression and PD-L1 status in tumor specimens prior to and 
while receiving treatment;
•
Characterize the protease activity and the activation of CX-2009 and CX-072 in optional 
on-treatment tumor biopsies and peripheral blood; and
•
Investigate the immunomodulatory activity of the treatment combination in optional 
on-treatment tumor biopsies (fixed and frozen).
2.3.8
Part E1 – CX-2009 + CX-072 Combination: Every 21-Day Dosing Regimen
The exploratory objectives of Part E1 are to determine the following in subjects treated with 
CX-2009 plus CX-072 every 21 days:
•
Explore potential predictive markers associated with clinical activity of the treatment 
combination such as CD166 expression and PD-L1 status in tumor specimens prior to and 
while receiving treatment;
•
Characterize the protease activity and the activation of CX-2009 and CX-072 in optional 
on-treatment tumor biopsies and peripheral blood; and
•
Investigate the immunomodulatory activity of the treatment combination in optional 
on-treatment tumor biopsies (fixed and frozen).
2.3.9
Part E2 – CX-2009 + CX-072 Combination: Every 21-Day Dosing Regimen
The exploratory objectives of Part E2 are to determine the following in subjects treated with 
CX-2009 plus CX-072 every 21 days:
•
Explore potential predictive markers associated with clinical activity of the treatment 
combination such as CD166 expression and PD-L1 status in tumor specimens prior to and 
while receiving treatment;
•
Characterize the protease activity and the activation of CX-2009 and CX-072 in optional 
on-treatment tumor biopsies and peripheral blood; and
•
Investigate the immunomodulatory activity of the treatment combination in optional 
on-treatment tumor biopsies (fixed and frozen).


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3
STUDY DESCRIPTION
3.1
Summary of Study Design
This is a Phase 1-2, open-label, multicenter, dose-finding, and proof of concept study for 
CX-2009 as monotherapy and (where permitted by local Health Authority) in combination with 
CX-072 in subjects with advanced solid tumors in the following indications: breast cancer (BC), 
castrate-resistant prostate carcinoma (CRPC), non-small cell lung carcinoma (NSCLC), OEC,
endometrial carcinoma (EC), HNSCC, or CCC. Table 4 provides an overview of the eligible 
tumor types and enrollment numbers for each part. These tumor types have been selected for 
their known high levels of CD166 expression and sensitivity to MTIs. A maximum of 
993 subjects will be enrolled into the study. No more than 40 subjects will be enrolled with a
given tumor type in each part.
The study is divided into 9 parts: Parts A, A2, B, C1, C2, D1, D2, E1, and E2 (see Figure 4), 
each designed to inform dose selection for the next phase of development. Part A is designed to 
define the MTD in 2 separate stages: a standard 3+3 escalation followed by a modified toxicity 
probability interval 2 (mTPI-2) cohort, in subjects receiving CX-2009 every 21 days. Part A2 is 
designed for biomarker evaluation (particularly Probody therapeutic activation) in order to 
further inform dose optimization. Part B is focused on expanding clinical experience in order to 
further define the safety profile at the MTD/RP2D as well as to obtain a preliminary assessment
of efficacy in a select number of cancers. Part B may be initiated as soon as the MTD/RP2D is 
defined in Part A and available data from Part A2 are reviewed in consultation with the Safety 
Review Committee (SRC; see Appendix E). Part C1 is designed to define the MTD/RP2D in 
subjects receiving CX-2009 every 14 days. Part C2 is focused on expanding clinical experience 
in order to further define the safety profile of CX-2009 and to obtain a preliminary assessment of 
efficacy when administered every 14 days at the MTD/RP2D. Dose expansion for CX-2009
monotherapy may occur under the every 21-day dosing regimen (Part B) and/or the every 14-day 
dosing regimen (Part C2), depending on available data from Parts A, A2, and C1.
Parts D and E involve co-administration of CX-2009 and CX-072. As such, these cohorts are 
only open to those countries in which the Health Authority permits these cohorts to activate. 
Part D1 is designed to define the MTD/RP2D in subjects receiving CX-2009 in combination with 
CX-072 every 14 days. Part D2 is focused on expanding clinical experience to further define the 
safety profile of CX-2009 administered in combination with CX-072 and to obtain a preliminary 
assessment of efficacy of the combination when administered every 14 days at the MTD/RP2D.
Part E1 is designed to define the MTD/RP2D in subjects receiving CX-2009 in combination with 
CX-072 every 21 days. Part E2 is focused on expanding clinical experience to further define the 
safety profile of CX-2009 administered in combination with CX-072 and to obtain a preliminary 
assessment of efficacy of the combination when administered every 21 days at the MTD/RP2D.


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Table 4.
Tumor Types and Enrollment by Part in Study CTMX-M-2009-001
Tumor Type
Study Part
A
A2
B
C1
C2
D1
D2
E1
E2
BC
X
X
TNBC
X
X
X
X
X
X
X
HR-positive/
HER2-negative BC
X
X
X
X
X
X
X
CRPC
  X a
NSCLC, including 
adenocarcinoma and squamous 
cell subtypes
X
X
X
X
X
X
X
X
X
OEC
  X a
X
X
X
X
X
X
X
X
EC
  X a
X
HNSCC
X
X
X
X
X
X
X
X
X
CCC
  X a
Total Enrollment (N  993):


b,c
24
 b,c

c

c
a Not an eligible tumor type for the mTPI-2 cohort.
b Dose expansion for CX-2009 monotherapy may occur under the every 21-day dosing regimen 
(Part B) and/or the every 14-day dosing regimen (Part C2), depending on available data from 
Parts A, A2, and C1. 
c No more than 40 subjects will be enrolled with a given tumor type in each part. 
BC = breast cancer; CCC = cholangiocellular carcinoma; CRPC = castrate-resistant prostate carcinoma; 
EC = endometrial carcinoma; HER2 = human epidermal growth factor receptor 2; HNSCC = head and
neck squamous cell carcinoma; HR = hormone receptor; NSCLC = non-small cell lung carcinoma; 
OEC = ovarian epithelial cancer; TNBC = triple-negative breast cancer.
The study will be conducted in US, UK, Spain, Netherlands, and Germany. Germany will 
participate only in Part B or C2 of the study. UK will not participate in Parts D1, D2, E1, and E2
of the study.
For all Parts, subjects who have enrolled in the study and have withdrawn prior to receiving the 
first dose will be designated as screen failures.
A definition of high CD166 expression is provided in Appendix I.
A DLT-evaluable subject is defined as one having received at least 1 dose of CX-2009 (or 
CX-2009 and CX-072) and then having completed the full DLT observation period (either 21 or 
28 days depending on the schedule), or one who subsequently withdrew due to a drug-related 
toxicity.


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Part A:
Dose escalation and determination of the MTD/RP2D of the CX-2009 monotherapy every 
21-day dosing regimen (n d 79: based on actual enrollment of initial cohorts and 
assumption of remaining cohorts and up to 38 total subjects enrolled into the mTPI-2
design cohort)
This part initiates with accelerated dose titration in 1 single-subject cohort (0.25 mg/kg, adjusted 
ideal body weight [AIBW]), followed by a standard 33 design to determine the MTD, and ends
in an mTPI-2 design cohort with up to 38 subjects with demonstrated high CD166 expression to 
determine the RP2D. The mTPI-2 design is a rule-based design similar to the 33 design and 
allows dose escalation/de-escalation. It is assumed to be of similar accuracy in determining the 
optimal dose as model-based design (Ji 2007) but allows a more flexible sample size. To 
understand the statistical rationale for the design, please refer to Section 9 and Appendix C.
Part A2:
Additional enrollment into previously cleared CX-2009 monotherapy dose levels from 
Part A (n d 42) for every 21-day dosing regimen
Part A2 will help to inform selection of the optimal MTD/RP2D by requiring measurable 
disease, mandating tumor biopsies to assess Probody therapeutic CX-2009 performance, and 
selecting for confirmed high CD166 expressing tumors by IHC.
Part B:
Dose expansion (proof of concept) at the MTD/RP2D of CX-2009 monotherapy every 
21-day dosing regimen with proof of concept in selected tumor types (maximum n d 200)
Part B will explore efficacy of CX-2009 by requiring measurable disease. Part B will enroll up to 
a total of 40 subjects each in 1 or more of the tumor types listed in Table 4. As of
November 2019, Part B will be initiated in subjects with HR-positive/HER2-negative BC at a 
dose of 7 mg/kg.
Part C1:
Dose escalation/de-escalation and determination of the MTD/RP2D of the CX-2009
monotherapy every 14-day dosing regimen (n d 24)
The highest dose level tested in this clinical study for CX-2009 was 10 mg/kg administered 
every 21 days, which successfully cleared the DLT evaluation period. The every 14-day dosing 
regimen equivalent of 10 mg/kg administered every 21 days is t7 mg/kg. In order to provide an 
additional margin of safety coverage for Part C1, the starting dose was 6 mg/kg, AIBW, 
administered every 14 days. The initial starting dose for Part C1 was not determined to be 
tolerated (see Section 1.3.4.1); a lower dose (4 mg/kg) will therefore be explored on the every 
14-day schedule. Subsequent dose escalation/de-escalation (if any) will be based upon the 


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observed safety tolerability profile as determined in consultation with the SRC. Prior to a dose 
escalation/de-escalation, a minimum of 3 evaluable subjects must be assessed (Figure 6). Part C1 
will include up to 24 subjects. Subjects will be selected from the following indications: TNBC, 
HR-positive/HER2-negative BC, NSCLC, OEC, or HNSCC.
Part C2:
Dose expansion at the MTD/RP2D of CX-2009 monotherapy every 14-day dosing regimen 
in selected tumor types(maximum n d 200)
Part C2 will explore efficacy of CX-2009. Part C2 will enroll up to a total of 40 subjects each in
1 or more of the tumor types listed in Table 4. Part C2 may be initiated as soon as the 
MTD/RP2D for the 14-day regimen is defined in consultation with the SRC and will only be 
initiated if, after the review of dose escalation data (Part C1), an every 14-day dosing regimen is 
considered for further development.
Part D1: 
Dose escalation/de-escalation and determination of the MTD/RP2D for the CX-2009 + 
CX-072 combination in an every 14-day dosing regimen in selected tumor types (n d 24)
Part D1 is only open to those countries in which the Health Authority permits the combination of 
CX-2009 and CX-072 to be investigated. The dose of CX-072 will be fixed at the RP2D (800 mg 
every 14 days). The starting dose for CX-2009 will be set at the every 14-day monotherapy 
RP2D as determined in Part C1. Lower starting doses may be used based on emerging safety 
data and in consultation with the SRC. The mTPI-2 design will be used to determine the 
MTD/RP2D for the combination dosed every 14 days. The following cohort’s dose will be 
increased or decreased according to the defined dose escalation rules based upon the observed 
safety tolerability profile as determined in consultation with the SRC. Prior to a dose 
escalation/de-escalation, a minimum of 3 evaluable subjects must be assessed per the mTPI-2
algorithm (Figure 6). Part D1 will enroll subjects in 1 or more of the tumor types listed in 
Table 4.
Part D2:
Dose expansion at the MTD/RP2D of the CX-2009 + CX-072 combination in an every 
14-day dosing regimen in selected tumor types (maximum n d 200)
Part D2 is only open to those countries in which the Health Authority permits the combination of 
CX-2009 and CX-072 to be investigated. Part D2 will explore efficacy of CX-2009 plus CX-072
for the every 14-day dosing regimen at the dose selected in Part D1. Part D2 will enroll up to a
total of 40 subjects each in 1 or more of the tumor types listed in Table 4. Part D2 may be 
initiated as soon as the MTD/RP2D for the 14-day combination regimen is defined in 
consultation with the SRC and will only be initiated if, after the review of dose escalation data 
(Part D1), an every 14-day combination dosing regimen is considered for further development.


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Part E1: 
Dose escalation and determination of the MTD/RP2D for the CX-2009 + CX-072
combination in an every 21-day dosing regimen in selected tumor types (n d 24) 
Part E1 is only open to those countries in which the Health Authority permits the combination of 
CX-2009 and CX-072 to be investigated. The dose of CX-072 will be fixed at the RP2D 
(1200 mg every 21 days). The starting dose of CX-2009 will be 7 mg/kg (the every 21-day 
monotherapy RP2D as determined in Parts A/A2). Lower starting doses may be used based on
emerging data and in consultation with the SRC. The mTPI-2 design will be used to determine 
the MTD/RP2D for the combination dosed every 21 days. The following cohort’s dose will be 
increased or decreased according to the defined dose escalation rules based upon the observed 
safety tolerability profile as determined in consultation with the SRC. Prior to a dose 
escalation/de-escalation, a minimum of 3 evaluable subjects must be assessed per the mTPI-2
algorithm (Figure 6). Part E1 will enroll subjects in 1 or more of the tumor types listed in 
Table 4.
Part E2:
Dose expansion at the MTD/RP2D of the CX-2009 + CX-072 combination in an every 
21-day dosing regimen in selected tumor types (maximum n d 200). 
Part E2 is only open to those countries in which the Health Authority permits the combination of 
CX-2009 and CX-072 to be investigated. Part E2 will explore efficacy of CX-2009 plus CX-072
for the every 21-day dosing regimen at the dose selected in Part E1. Part E2 will enroll up to a 
total of 40 subjects each in 1 or more of the tumor types listed in Table 4. Part E2 may be 
initiated as soon as the MTD/RP2D for the 21-day combination regimen is defined in 
consultation with the SRC and will only be initiated if, after the review of dose escalation data 
(Part E1), an every 21-day combination dosing regimen is considered for further development.
Allocation of Subjects Between Parts C, D, and E
In case Parts C, D, and E are open for enrollment concurrently and subjects meet the eligibility 
criteria for all parts, the Sponsor in conjunction with the Principal Investigator will determine to 
which part the subjects are allocated. The Sponsor will determine which tumor types will be 
selected for additional evaluation for Parts B, C2, D2, and E2.


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Figure 4.
Study Design Schema: Parts A, A2, and B (Every 21-Day Dosing Regimen)
a Part A eligible tumor types: BC, CRPC, NSCLC, OEC, EC, HNSCC, and CCC.
b Part A2 restricted to subjects with BC, NSCLC, OEC, EC, and HNSCC.
c Part A mTPI-2 cohort eligible tumor types: BC, NSCLC, and HNSCC.
d Part B eligible tumor types: TNBC, HR-positive/HER2-negative BC, NSCLC, OEC, and HNSCC.
Note: Parts A (mTPI-2 cohort only) and A2 will enroll subjects with confirmed high CD166 expressing tumors.
BC = breast cancer; CCC = cholangiocellular carcinoma; CRPC = castrate-resistant prostate carcinoma; EC = endometrial carcinoma; HER2 = human epidermal growth factor 
receptor 2; HNSCC = head and neck squamous cell carcinoma; HR = hormone receptor; mpk = mg/kg; MTD = maximum tolerated dose; mTPI-2 = modified toxicity probability 
interval 2; NSCLC = non-small cell lung carcinoma; OEC = ovarian epithelial cancer; RP2D = recommended Phase 2 dose; TNBC = triple negative breast cancer.


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3.1.1
Duration of Treatment, Follow-Up, and Study Completion
The study is divided into periods with associated evaluations and procedures that must be 
performed at specific time points. The schedules of procedures in Appendix B summarize the 
frequency and timing of efficacy, safety, and other study measurements. Refer to the Core 
(Appendix A) for a description of each procedure. 
As with any Phase 1 study, an individual subject’s participation in the study is difficult to 
predict. It is estimated that average treatment will last approximately 6 months, followed by
Follow-Up contact every 3 to 6 months for another 1 to 2 years, or as long as the subject remains 
alive (Figure 5).
Figure 5.
Study Periods
Notes: An EOT Visit will be conducted 30 days (r7 days) after the last infusion of study treatment. Follow-Up: If subject has not 
had progression, imaging assessments will continue until progression is documented. If subject had documented progression, the
subject may continue in the study if experiencing clinical benefit (as assessed by the Investigator) following consultation with the 
Medial Monitor; otherwise, the subject will continue in survival Follow-Up Visits every 3 months (r14 days) after the EOT Visit 
for 1 year and then every 6 months (r14 days) (this may be by telephone), or until death. Subsequent cancer treatment will be 
collected. Survival Follow-Up will be done every 3 months (r14 days) as described above.
DLT = dose-limiting toxicity; EOT = end of treatment; IV = intravenous; q14 = every 14; q21 = every 21.
Following the completion of study treatment, subjects with progressive disease per RECIST (or 
irRECIST, for subjects in Parts D1, D2, E1, and E2) will return for an End of Treatment (EOT) 
Visit and then enter the Follow-Up Period for monitoring of survival. Subjects who for other 
reasons stop study drug treatment and have SD, PR, or complete response will enter the 
Follow-Up Period for monitoring of DOR and PFS. 
The study will be completed approximately 2 years from the date the last subject is enrolled or 
when the last subject has completed treatment and the last Follow-Up Visit.
The EOT Visit will be conducted 30 days (r7 days) after the last infusion of study treatment.
Once a subject experiences progressive disease, the subject may continue in the study if 
experiencing clinical benefit (as assessed by the Investigator) following consultation with the 
Medial Monitor; otherwise, the subject will continue to be monitored for survival. All subjects 
will return for Follow-Up Visits every 3 months after the EOT Visit for 1 year and then every 
6 months to ensure resolution of toxicities and as applicable, confirm negative pregnancy status.


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During the EOT Visit, subjects will be followed for resolution of toxicity. Women of 
childbearing potential will undergo monthly pregnancy testing while on study drug and through 
50 days after the last dose of CX-2009, or 6 months after the last dose of CX-072, as applicable, 
whichever is later. Thereafter, Follow-Up Visits will be conducted for survival information and 
may be performed by telephone.
3.2
Part A (CX-2009 Monotherapy):
Dose Escalation and Determination of MTD/RP2D for Every 21-Day Dosing 
Regimen (n d 79: Based on Actual Enrollment of Initial Cohorts and Assumption of 
Remaining Cohorts and Up to 38 Total Subjects Enrolled Into the Modified Toxicity 
Probability Interval-2 Design Cohort)
The primary objectives of Part A are to assess safety, tolerability, and to determine the 
MTD/RP2D and DLTs of CX-2009 when administered as monotherapy. Up to 79 subjects with 
measurable advanced or recurrent solid tumors will be enrolled in the dose escalation portion of 
the study to determine the MTD/RP2D. As of November 2019, this cohort was closed with 
47 subjects enrolled.
One subject will be enrolled into the first cohort until the first dose level is enrolled and treated 
successfully. Should a subject in cohort 1 experience a tGrade 2 AE that is at least possibly 
related to the study drug, 2 more subjects will be enrolled at that dose level and evaluated based 
on 33 design rules. Should the first subject in cohort 1 experience a DLT, the dose level will be 
expanded to 3 subjects and if there is no additional DLT, the dose level will be expanded to 
6 subjects. All subsequent cohorts will utilize a 33 design and will enroll sufficient evaluable 
subjects to allow for DLT evaluation. Dosing increments will be less than 100.0% if a subject in 
the single-subject cohort experiences a tGrade 2 toxicity. The first subject in each new dose 
cohort will be dosed at least 24 hours prior to any other subjects in that cohort being dosed, to 
allow for observation of possible severe and/or serious acute (eg, infusion-related) toxicities that 
might affect subsequent subject enrollment or dosing decisions.
Enrollment will continue in each cohort until the MTD or the RP2D is defined, or the highest 
dose (ie, 10 mg/kg, AIBW) has been tested and deemed safe, whichever is lower. AIBW should 
be applied using the formula provided in Appendix F.
Once the MTD is defined or the highest dose is tested (ie, 10 mg/kg, AIBW), up to 38 subjects 
can be enrolled at the MTD to refine dose selection using mTPI-2, a rule-based design similar to
the 3+3 design that allows dose escalation/de-escalation. Up to 6 subjects can be treated at each 
dose level and up to 14 subjects can be treated at the identified MTD/RP2D dose level. 
Assuming that up to 5 dose levels (6 mg/kg to 10 mg/kg, AIBW) may be explored in the mTPI-2
cohort, a maximum sample size of 38 subjects may be enrolled. AEs that meet DLT criteria 
(within the 21-day DLT period) and delayed AEs that lead to treatment 
interruption/discontinuation within the first 6 weeks, thus encompassing the first 3 doses (DLT 
rate d30.0%; delayed AE rate d20.0%), will be monitored. Decision for dose 


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escalation/de-escalation will be made by the Sponsor in consultation with the SRC guided by the 
decision-making table (Appendix C). The selection of MTD/RP2D will be based predominantly 
on safety and may take other factors into account such as PK/pharmacodynamics (PD) and 
clinical activity. 
The mTPI-2 cohort will evaluate up to 5 dose levels based on DLT events and TRAEs leading to 
treatment delay or discontinuation, including events of special interest (eg, ocular toxicity and 
peripheral neuropathy). As events of special interest have been observed at later time points, 
TRAEs leading to treatment interruption (ie, missed dose) or treatment discontinuation will be 
evaluated over an extended interval that encompasses the first 3 infusions (42 days). An event for 
the mTPI-2 cohort is defined as either a DLT or a TRAE leading to treatment interruption 
(ie, missed dose) or treatment discontinuation. The decision-making tables for the mTPI-2 cohort 
are provided in Appendix C.
For dosing, AIBW should be applied (Appendix F).
Subjects may be permitted individual dose escalations to previously cleared dose levels 
following consultation with the Medical Monitor.
The DLT assessment period for dose escalation is 21 days.
Subjects in Part A who discontinue study drug administration for reasons other than DLTs may 
be replaced to ensure the minimum number of subjects required for DLT evaluation is enrolled. 
As of November 2019, the RP2D for CX-2009 administered every 21 days was determined to be 
7 mg/kg. For justification of this dose, refer to Sections 1.3.4.1 and 5.2.
3.3
Dose-Limiting Toxicity
All AEs will be captured according to the National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI CTCAE) v4.03 (and considered for assessment of DLTs as 
outlined by the criteria in Table 5).


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Table 5.
Dose-Limiting Toxicity
Suspected DLT Criteria
DLT
Yes
No
Grade 5 AEs judged by the Investigator to be treatment-related or judged by the 
Sponsor as treatment-related, regardless of Investigator attribution.
X
Grade 4 AEs* judged by the Investigator to be treatment-related or judged by the 
Sponsor as a DLT, regardless of Investigator attribution.
X
*Grade 4 Exceptions
• The following Grade 4 hematologic AEs:
–
Grade 4 lymphopenia; and
–
Grade 4 neutropenia lasting <7 days that is not associated with fever, or other 
clinically significant symptoms, or is corrected with supportive measures 
(eg, growth factors)/appropriate management.
• Grade 4 electrolyte imbalances/abnormalities that are not associated with clinical 
sequelae and are corrected with supplementation/appropriate management within 
72 hours of their onset.
X
Grade 3 AEs** judged by the Investigator to be treatment-related or by the 
Sponsor, regardless of Investigator attribution, including:
• Any Grade 3 AE that does not resolve to Grade d1 or to baseline with appropriate 
therapies within 7 days of onset;
• Any Grade 3 febrile neutropenia;
• Any clinically significant Grade 3 CNS event;
• Any Grade 3 neurotoxicity; and
• Any Grade 3 ocular toxicity (limiting self-care ADL) that does not resolve within 
7 days and which did occur despite proper application of preventive measures.
X
**Grade 3 Exceptions
• Isolated Grade 3 electrolyte imbalances/abnormalities that are not associated with 
clinical sequelae and are corrected with supplementation/appropriate 
management within 72 hours of their onset;
• Grade 3 asthenia which persists for up to 7 days;
• “Tumor flare” – defined as local pain, irritation, or rash localized at sites of 
known or suspected tumor; and
• Grade 3 infusion reaction which resolves to dGrade 1 within 6 hours.
X
Grade 2 pneumonitis, Guillain-Barré syndrome, transverse myelitis, myocarditis, 
pericarditis, and arrhythmias necessitating discontinuation of CX-072.
X
Any clinically significant immune-mediated AE judged by the Investigator to be
related to CX-072 that necessitates discontinuation of CX-072.
X
ADL = activities of daily living; AE = adverse event; CNS = central nervous system; DLT = dose-limiting toxicity.
Enrollment will continue in each cohort until the MTD or the RP2D is defined, or the highest 
dose (ie, 10 mg/kg, AIBW) has been tested and deemed safe, whichever is lower. Interim dose 
level(s) may be explored in consultation with the SRC.
The first subject in each new dose cohort will be dosed at least 24 hours prior to any other 
subjects in that cohort to allow for observation of possible severe and/or serious acute 
(eg, infusion-related) toxicities that might affect subsequent subject enrollment or dosing
decisions. The first dose level will be enrolled as a single-subject cohort. Dose escalation rules 
are outlined in Table 6.


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Table 6.
Monotherapy Dose Escalation Rules for 33 Design
3.4
Part A2 (CX-2009 Monotherapy):
Additional Enrollment Into Previously Cleared Dose Levels From Part A (n d 42)
for Every 21-Day Dosing Regimen
Part A2 will help to inform selection of the optimal MTD/RP2D by investigating Probody 
therapeutic concentration and activation within the tumor. For that purpose, subjects will be 
asked to consent to on-treatment tumor biopsies. 
Part A2 will initiate enrollment after the 4 mg/kg cohort in Part A has completed the DLT period 
and with the recommendation of the SRC. Six subjects must be enrolled into each cohort before 
the next sequential cohort can be enrolled. Doses administered in Part A2 can never exceed the 
most recently cleared dose in Part A. All toxicities observed in Part A2, regardless of whether 
they are observed early or late in the dosing course, will be reviewed by the SRC and used to 
make recommendations for further enrollment in all parts of the study.
Up to a total of 42 subjects will be enrolled at up to 7 dose levels with 6 subjects per cohort per 
dose. As of November 2019, this cohort was closed with 39 subjects enrolled. 
Available data from Part A2 will be considered by the SRC when making dosing 
recommendations and performing cohort review in Part A. As of November 2019, the RP2D for 
further study of CX-2009 monotherapy when given every 21 days in Part B was determined to be
7 mg/kg; this dose will continue to be assessed for safety and may be modified if supported by 
the data.
Part A2 will be restricted to subjects with BC, NSCLC, OEC, EC, and HNSCC. These tumor 
types have been selected for their responsiveness to MTIs and general availability of lesion safe 
to be biopsied.
Tumor biopsies are required 3 to 5 days after the first dose of CX-2009. To enroll a subject in 
Part A2, the Investigator must consider the subject safe to biopsy and the subject must consent to 
biopsy collection.
Number of 
Subjects 
in Cohort
Number of
DLTs/Subjects
Action
1
0/1
Monotherapy dose completed
1
1/1
Add 2 additional subjects to the cohort (add 3 additional subjects if no further 
DLTs are observed); all subsequent cohorts 3+3 design
3
0/3
Monotherapy dose completed
3
1/3
Add 3 additional subjects to the cohort
3
t2/3
Dose level is above the MTD, escalation ceases
6
1/6
Monotherapy dose completed
6
t2/6
Dose level is above the MTD, escalation ceases
DLT = dose-limiting toxicity; MTD = maximum tolerated dose.


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3.5
Part B (CX-2009 Monotherapy):
Dose Expansion/Proof of Concept at MTD/RP2D for Every 21-Day Dosing Regimen
With Proof of Concept in Selected Tumor Types (Maximum n d 200)
To explore efficacy of CX-2009, indication-specific expansion cohorts will be opened to obtain 
preliminary evidence of clinical activity. Part B will enroll up to a total of 40 subjects each in 
1 or more of the tumor types listed in Table 4. As of November 2019, the RP2D of CX-2009 was 
determined to be 7 mg/kg on the 21-day schedule. Part B will begin enrollment; the initial tumor 
type selected will be HR-positive/HER2-negative breast cancer. Additional tumor types may also 
be selected.
If subjects with a specific tumor type are previously treated at the MTD/RP2D in Part A2, they 
may count towards the first 14 subjects targeted for that tumor type for Part B.
Note: Dose expansion for CX-2009 monotherapy may occur under the every 21-day dosing 
regimen (Part B) and/or the every 14-day dosing regimen (Part C2), depending on available data 
from Parts A, A2, and C1. Selection of the regimen for dose expansion will be made in 
consultation with the SRC.
3.6
Part C1 (CX-2009 Monotherapy):
Dose Escalation/De-escalation and Determination of MTD/RP2D for Every 14-Day
Dosing Regimen (n d 24)
Part C1 initiated at a dose level of 6 mg/kg every 14 days, AIBW (selected from among the 
following indications: BC, NSCLC, or HNSCC). Prior to a dose escalation/de-escalation, a 
minimum of 3 evaluable subjects must be assessed (Figure 6). Subsequent dose 
escalation/de-escalation (if any) will be based upon the observed safety tolerability profile as 
determined in consultation with the SRC. 
Part C1 will evaluate dose levels based on DLT events and TRAEs leading to treatment delay or 
discontinuation, including events of special interest (eg, ocular toxicity and peripheral 
neuropathy).
AEs that meet DLT criteria (within the 28-day DLT period) and delayed AEs that lead to 
treatment interruption/discontinuation within the first 6 weeks, thus encompassing the first 
3 doses (DLT rate d30.0%; delayed AE rate d20.0%), will be monitored. Decision for dose 
escalation/de-escalation will be made by the Sponsor in consultation with the SRC guided by the 
decision-making table (Appendix C). The selection of MTD/RP2D with an every 14-day dosing 
regimen will be based predominantly on safety and may take other factors into account such as 
PK/PD and clinical activity.
Subjects who discontinue study drug administration for reasons other than DLTs may be 
replaced to ensure the minimum number of subjects required for DLT evaluation is enrolled. 


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3.7
Part C2 (CX-2009 Monotherapy):
Dose Expansion at the MTD/RP2D for Every 14-Day Dosing Regimen in 
Selected Tumor Types (Maximum n d 200)
To explore efficacy of CX-2009 for every 14-day dosing regimen, indication-specific expansion 
cohorts will be opened to obtain preliminary evidence of clinical activity. Part C2 will enroll up
to a total of 40 subjects each in 1 or more of the tumor types listed in Table 4. These tumor types 
have been selected for their responsiveness to MTIs and general availability of lesion safe to be 
biopsied. Part C2 may be initiated as soon as the MTD/RP2D for the 14-day regimen is defined 
in consultation with the SRC and will only be initiated if, after the review of dose escalation data 
(Part C1), an every 14-day dosing regimen is considered for further development.
Allocation of Subjects Between Parts C, D, and E. In case Parts C, D, and E are open for 
enrollment concurrently and subjects meet the eligibility criteria for all parts, the Sponsor in 
conjunction with the Principal Investigator will determine to which part the subjects are 
allocated. The Sponsor will determine which tumor types will be selected for additional 
evaluation for Parts B, C2, D2, and E2.
Note: Dose expansion for CX-2009 monotherapy may occur under the every 21-day dosing 
regimen (Part B) and/or the every 14-day dosing regimen (Part C2), depending on available data 
from Parts A, A2, and C1. Selection of the regimen for dose expansion will be made in 
consultation with the SRC.
3.8
Part D1 (CX-2009 + CX-072):
Dose Escalation/De-escalation and Determination of MTD/RP2D for Every 14-Day 
Dosing Regimen in Selected Tumor Types (n d 24)
Part D1 is only open to those countries in which the Health Authority permits the combination of 
CX-2009 and CX-072 to be investigated. The dose of CX-072 will be fixed at the RP2D (800 mg 
every 14 days). The starting dose for CX-2009 will be set at the every 14-day monotherapy 
RP2D as determined in Part C1. Lower starting doses may be used based on emerging safety 
data and in consultation with the SRC. The mTPI-2 design will be used to determine the 
MTD/RP2D for this schedule. The following cohort’s dose will be increased or decreased 
according to the defined dose escalation rules based upon the observed safety tolerability profile 
as determined in consultation with the SRC. Prior to a dose escalation/de-escalation, a minimum 
of 3 evaluable subjects must be assessed per the mTPI-2 algorithm (Figure 6). Part D1 will enroll
subjects in 1 or more of the tumor types listed in Table 4. The tumor types have been selected for 
their responsiveness to MTIs and general availability of lesion safe to be biopsied.
Part D1 will evaluate dose levels based on DLT events and TRAEs leading to treatment delay or 
discontinuation, including events of special interest (eg, ocular toxicity and peripheral 
neuropathy). 


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AEs that meet DLT criteria (within the 28-day DLT period) and delayed AEs that lead to 
treatment interruption/discontinuation within the first 6 weeks, thus encompassing the first 
3 doses (DLT rate d30.0%; delayed AE rate d20.0%), will be monitored. Decision for dose 
escalation/de-escalation will be made by the Sponsor in consultation with the SRC guided by the 
decision-making table (Appendix C). The selection of MTD/RP2D will be based predominantly 
on safety and may take other factors into account such as PK/PD and clinical activity.
Subjects who discontinue study drug administration for reasons other than DLTs may be 
replaced to ensure the minimum number of subjects required for DLT evaluation is enrolled. 
3.9
Part D2 (CX-2009 + CX-072):
Dose Expansion for Every 14-Day Dosing Regimen in Selected Tumor Types
(Maximum n d 200)
Part D2 is only open to those countries in which the Health Authority permits the combination of 
CX-2009 and CX-072 to be investigated. To explore efficacy of CX-2009 plus CX-072 for the 
every 14-day dosing regimen, indication-specific expansion cohorts will be opened to obtain 
preliminary evidence of clinical activity. Part D2 will enroll up to a total of 40 subjects each in 
1 or more of the tumor types listed in Table 4. The tumor types have been selected for their 
responsiveness to MTIs and general availability of lesion safe to be biopsied. The expansion may 
be initiated as soon as the MTD/RP2D for the 14-day regimen is defined in consultation with the 
SRC and will only be initiated if after the review of dose escalation data (Part D1), an every 
14-day dosing regimen is considered for further development.
3.10
Part E1 (CX-2009 + CX-072):
Dose Escalation and Determination of MTD/RP2D for Every 21-Day Dosing 
Regimen in Selected Tumor Types (n d 24)
Part E1 is only open to those countries in which the Health Authority permits the combination of 
CX-2009 and CX-072 to be investigated. The dose of CX-072 will be fixed at the RP2D 
(1200 mg every 21 days). The starting dose of CX-2009 will be 7 mg/kg (the every 21-day 
monotherapy RP2D as determined in Parts A/A2). Lower starting doses may be used based on
emerging data and in consultation with the SRC. The mTPI-2 design will be used to determine 
the MTD/RP2D for this schedule. The following cohort’s dose will be increased or decreased
according to the defined dose escalation rules based upon the observed safety tolerability profile 
as determined in consultation with the SRC. Prior to a dose escalation/de-escalation, a minimum 
of 3 evaluable subjects must be assessed per the mTPI-2 algorithm (Figure 6). Part E1 will enroll
subjects in 1 or more of the tumor types listed in Table 4. The tumor types have been selected for 
their responsiveness to MTIs and general availability of lesion safe to be biopsied.
Part E1 will evaluate dose levels based on DLT events and TRAEs leading to treatment delay or 
discontinuation, including events of special interest (eg, ocular toxicity and peripheral 
neuropathy). 


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AEs that meet DLT criteria (within the 21-day DLT period) and delayed AEs that lead to 
treatment interruption/discontinuation within the first 6 weeks, thus encompassing the first 
3 doses (DLT rate d30.0%; delayed AE rate d20.0%), will be monitored. Decision for dose 
escalation/de-escalation will be made by the Sponsor in consultation with the SRC guided by the 
decision-making table (Appendix C). The selection of MTD/RP2D will be based predominantly 
on safety and may take other factors into account such as PK/PD and clinical activity.
Subjects who discontinue study drug administration for reasons other than DLTs may be 
replaced to ensure the minimum number of subjects required for DLT evaluation is enrolled. 
3.11
Part E2 (CX-2009 + CX-072):
Dose Expansion for Every 21-Day Dosing Regimen in Selected Tumor Types 
(Maximum n d 200)
Part E2 is only open to those countries in which the Health Authority permits the combination of 
CX-2009 and CX-072 to be investigated. To explore efficacy of CX-2009 plus CX-072 for the 
every 21-day dosing regimen, indication-specific expansion cohorts will be opened to obtain 
preliminary evidence of clinical activity. Part E2 will enroll up to a total of 40 subjects each in 
1 or more of the tumor types listed in Table 4. The tumor types have been selected for their 
responsiveness to MTIs and general availability of lesion safe to be biopsied. The expansion may 
be initiated as soon as the MTD/RP2D for the 21-day regimen is defined in consultation with the 
SRC and will only be initiated, if after the review of dose escalation data (Part E1), an every 
21-day dosing regimen is considered for further development.


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4
SELECTION AND WITHDRAWAL OF SUBJECTS 
A subject may be approached for informed consent so that archival tumor tissue may be tested 
for CD166 expression (prior to the subject being otherwise eligible for entry into this study). An 
abbreviated informed consent form would be used for this purpose.
After signing the informed consent form (ICF), subjects will be evaluated for 
CTMX-M-2009-001 study eligibility during the Screening Period (no more than 30 days before 
study drug administration) according to the following inclusion/exclusion criteria.
4.1
Inclusion Criteria
Subjects who fulfill the following criteria at Screening will be eligible for admission into the 
study:
1. Histologically confirmed diagnosis of active metastatic or locally advanced unresectable 
solid tumor in subjects who have disease progression after treatment with available therapies 
that are known to confer clinical benefit, or who are intolerant to treatment, in the following 
indications (with guidance for standard treatment below).
Subjects participating in Parts A and A2 and all subjects except those with 
HR-positive/HER2-negative must submit an archival tumor tissue sample to the central 
laboratory for evaluation of CD166 expression and demonstrate confirmed high CD166 
expression by IHC. For subjects without available archival tumor tissue, only those subjects 
who consent and for whom the Principal Investigator determines that tumor biopsy can be 
safely performed can undergo biopsy collection for the purpose of determining eligibility.
Eligible Indications, by Part: see Table 4
Criterion Specific to Parts B, C, D, and E:
•
Subjects must have received the standard prior treatments for metastatic or advanced 
unresectable measurable disease as outlined below:
Standard Prior Treatments, by Tumor Type:
TNBC (Parts B, C1, C2, D1, D2, E1, and E2):
•
Histologically or cytologically confirmed TNBC based on the most recent analyzed 
biopsy or other pathology specimen. Pathologic results should show HR-positive <10%
by IHC and HER2-negative disease by American Society for Clinical Oncology (ASCO)
guidelines (Allison 2020); the Principal Investigator should use his/her best medical 
judgment to decide whether the subject’s BC should be best managed as HR-positive or 
triple-negative disease;
•
Refractory to or relapsed after 1 but no more than 3 prior standard therapeutic regimens 
for advanced/metastatic TNBC (for regimen counting rules, see Appendix J); rapid 
progression following adjuvant therapy (<12 months from last dose) will count as a 


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regimen for advanced/metastatic disease. If locally approved, this must include an ICI in 
combination with cytotoxic chemotherapy (such as atezolizumab with nab-paclitaxel).
Standard therapeutic regimens may include cytotoxic therapy, an ADC, a polyadenosine 
diphosphate ribose (PARP) inhibitor, or an investigational therapy;
•
Subjects must have received a taxane (paclitaxel or docetaxel)-based regimen in any 
setting (neoadjuvant, adjuvant, localized or advanced/metastatic disease); and
•
Parts D and E: PD-L1 expression data are not required; subjects with known PD-L1 
negative disease (using any commercially available antibody) are not eligible;
HR-positive/HER2-negative BC (Parts B, C1, C2, D1, D2, E1, and E2):
•
Tumor tissue must be obtained and forwarded to the central laboratory for determination 
of CD166 expression by IHC but this result is not required during the screening period;
•
Refractory to or relapsed after at least 2 and no more than 4 prior systemic chemotherapy 
regimens for metastatic BC (not including single-agent hormonal therapy);
•
An eligible subject must have received:
–
At least 1 prior anticancer hormonal treatment in any setting (neoadjuvant, adjuvant, 
locally advanced or metastatic disease);
–
At least 1 cyclin-dependent kinase inhibitor 4/6 in any setting (eg, palbociclib, 
abemaciclib, ribociclib, or a member of this class);
–
At least 1 prior cytotoxic chemotherapy in the metastatic setting (eg, 
microtubulin-targeted agents including taxanes, antimetabolites, anthracyclines, 
alkylating agents, topoisomerase 1 or 2 inhibitor, etc), or mammalian target of rapamycin 
inhibitor;
–
Investigational drugs and drugs that are commercially available but not approved for BC 
count as a regimen (for regimen counting rules, see Appendix J); and 
•
Parts D and E: PD-L1 expression data are not required; subjects with known PD-L1 
negative disease (using any commercially available antibody) are not eligible;
CRPC (Part A):
•
Received at least 1 prior therapy (eg, abiraterone  prednisone, or 
docetaxel  prednisone, or enzalutamide);
NSCLC, Including Adenocarcinoma and Squamous Cell Subtypes (All Parts):
•
No more than 3 prior regimens for locally advanced/metastatic disease (including 
chemoradiation);
•
Should have received at least 1 platinum-containing regimen, at least 1 taxane-containing 
regimen, and 1 anti–PD-1 or anti–PD-L1 therapy (if anti-PD-1 or anti-PD-1 therapy is 
approved and available for the subject’s indication in their locality); and 
•
Subjects harboring known genomic aberrations for which an approved targeted therapy is 
locally available (eg, non-resistant epidermal growth factor receptor [EGFR] mutations, 


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EGFR T790M mutation, anaplastic lymphoma kinase (ALK) rearrangement, ROS 
rearrangement, BRAF V600E mutation) must have received at least 1 prior treatment 
with an approved targeted therapy;
OEC (All Parts):
•
Subjects must have platinum-resistant or platinum-refractory ovarian carcinoma 
(progression within 180 or 90 days from last dose of platinum); no more than 2 prior 
platinum-containing regimens are permitted;
•
Subjects with platinum-resistant disease must have also progressed on chemotherapy plus 
bevacizumab; 
•
Subjects with BRCA mutations must be refractory to or ineligible per local prescribing 
guidelines for PARP inhibitors (eg, olaparib or rucaparib) if approved and available; and
•
Subjects may have received up to 3 regimens for advanced/metastatic disease;
EC (Parts A, A2):
•
Should have received at least 1 platinum-containing regimen for extra-uterine or 
advanced disease;
HNSCC (All Parts):
•
Must have received a platinum-containing regimen and anti–PD-1 if approved and 
available for subject’s indication in their locality;
•
Must have progressed on at least 1 additional regimen for advanced/metastatic disease 
including either a taxane, cetuximab, or methotrexate; and
•
Subjects may have received up to 3 regimens for advanced/metastatic disease;
CCC (Part A):
•
Failed at least 1 prior line of a gemcitabine-containing regimen;
2. Agrees to provide tumor tissue; archival, new, or recent acquisition confirmed to be available 
prior to initiation of study drug for performance of correlative tissue and cellular studies from 
a tumor site not previously irradiated:
•
Part A2: subjects must consent to an on-treatment tumor biopsy at 3 to 5 days after the 
first dose of CX-2009; and
•
Parts B and C2 (monotherapy dose expansions): at least 7 subjects of each tumor type 
must consent to provide a pretreatment and on-treatment tumor biopsy and peripheral 
blood samples 3 to 5 days after the first dose of CX-2009; 
3. Evaluable or measurable disease required for dose escalation (Part A) and measurable disease 
per RECIST v1.1 required for all other parts;
4. Subjects with treated brain metastases (surgery, stereotactic radiation, whole brain radiation, 
or a combination of these modalities) are eligible if the subject’s brain metastases have been 
documented to be stable by head imaging (2 scans at least 28 days apart, including the scan 


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obtained during the screening period) and the screening clinical examination and the subject 
does not require radiation therapy, or high-dose steroids (defined as prednisone 10 mg/day or 
its equivalent). Active screening for subjects not known to have brain metastases (eg, brain 
computed tomography or magnetic resonance imaging) is not required;
5. At least 18 years of age;
6. Eastern Cooperative Oncology Group performance status of 0 or 1;
7. Anticipated life expectancy of at least 3 months;
8. Screening laboratory values must meet the following criteria: 
•
Absolute neutrophil count t1500/PL;
•
Platelet count t75 u 103/PL (must not have been transfused within previous 10 days);
•
Hemoglobin t9.0 g/dL (may have been transfused);
•
Serum creatinine d1.5 u institution’s upper limit of normal (ULN);
•
AST d2.5 u institution’s ULN; ALT d2.5 u institution’s ULN (AST, ALT <5 u ULN for 
subjects with CCC with liver metastases);
•
Serum total bilirubin d1.5 u institutional ULN (total bilirubin must be d3.0 u institution’s 
ULN in subjects with Gilbert’s syndrome). Serum total bilirubin d3.0 u institutional ULN 
for subjects with CCC with liver metastases;
•
For Parts B, C, D, and E only:
–
Hemoglobin t 9.0 g/dL (without transfusion within 30 days of Cycle 1 Day 1);
–
AST, ALT, and alkaline phosphatase (ALP) îinstitution’s ULN (without 
exemption for liver or bone metastases);
–
International normalized ratio (INR) and activated partial thromboplastin time (aPTT) 
 × ULN (unless subject is on therapeutic anticoagulation, at which time the INR 
and aPTT must be in the target therapeutic anticoagulation range); and
–
6HUXPDOEXPLQ g/dL.
9. Women of childbearing potential (defined as women who have experienced menarche and
who are not permanently sterile or postmenopausal; postmenopausal is defined as 
12 consecutive months with no menses without an alternative medical cause) and males must 
agree to use a highly effective method of contraception prior to study entry, while on study
drug, and for a period of 50 days after the last dose of CX-2009 or 6 months after the last 
dose of CX-072, whichever is later;
•
Highly effective methods of contraception which result in a low failure rate 
(ie, 1.0% per year) when used consistently and correctly include implants, injectables, 
combined hormonal contraceptives, some intrauterine devices, sexual abstinence, or a 
vasectomized partner;
–
True abstinence, when in line with the preferred and usual lifestyle of the subject, is 
considered a highly effective method only if defined as refraining from heterosexual 


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intercourse during the entire period of risk associated with the study treatments. 
(Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation method] 
and withdrawal are not acceptable methods of contraception.); and
10. The ability to understand and the willingness to sign a written informed consent document 
and adhere to study schedule and prohibitions.
4.2
Exclusion Criteria
Subjects who fulfill any of the following criteria at Screening will not be eligible for admission:
1. Neuropathy !Grade 1;
2. Active or chronic corneal disorder, including but not limited to the following: Fuchs corneal 
dystrophy (requiring treatment), history of corneal transplantation, active herpetic keratitis, 
and also active ocular conditions requiring ongoing treatment/monitoring such as wet 
age-related macular degeneration requiring intravitreal injections, active diabetic retinopathy 
with macular edema, presence of papilledema, and acquired monocular vision. In addition, 
the following exclusions apply:
•
Subjects with cataract surgery until 30 days after last dose of steroid eye drops calculated 
from Cycle 1 Day 1 (subjects with untreated cataracts are not excluded);
•
Subjects with prior refractive surgery of any type (eg, Lasik surgery) within 1 year prior 
to Cycle 1 Day 1;
•
Subjects with any other type of recent ocular surgery excluded until 30 days after last 
dose of eye drops calculated from Cycle 1 Day 1 (not including artificial tears); or
•
Subjects whose severe or refractory dry eye or other ocular surface disease requires 2 or 
more ophthalmic medications (not including artificial tears);
3. Serious concurrent illness, including, but not limited to the following: 
•
Clinically relevant active infection including known active hepatitis B or C, human 
immunodeficiency virus infection, or cytomegalovirus infection or any other known 
concurrent infectious disease, requiring IV antibiotic, antiviral, or antifungal therapy
within 2 weeks of study enrollment;
•
History of or current active autoimmune diseases, including but not limited to myasthenia 
gravis, inflammatory bowel diseases, rheumatoid arthritis, autoimmune thyroiditis which 
is not a sequela of prior immune checkpoint therapy, autoimmune hepatitis, systemic 
sclerosis, systemic lupus erythematosus, autoimmune vasculitis, autoimmune 
neuropathies, or type 1 insulin dependent diabetes mellitus;
•
Significant cardiac disease such as recent myocardial infarction (d6 months prior to 
Day 1), unstable angina pectoris, uncontrolled congestive heart failure (New York Heart 
Association >class II), uncontrolled hypertension (NCI CTCAE v4.03 Grade 3 or higher), 
uncontrolled cardiac arrhythmias, severe aortic stenosis, or tGrade 3 cardiac toxicity 
following prior chemotherapy;


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•
History of multiple sclerosis or other demyelinating disease, Eaton-Lambert syndrome 
(para-neoplastic syndrome), history of hemorrhagic or ischemic stroke within the last 
6 months, or alcoholic liver disease;
•
Non-healing wound(s) or ulcer(s) except for ulcerative lesions caused by the underlying 
neoplasm;
•
Psychiatric illness/social situations that would limit compliance with study requirements;
or
•
Interstitial lung disease irrespective of etiology;
4. Advanced or metastatic Stage IV NSCLC subjects with known EGFR or ALK genomic 
alterations unless they have progressed on treatment with appropriate targeted therapy;
5. Any other anticancer treatment such as chemotherapy, immunotherapy, biochemotherapy, 
radiotherapy, investigative therapy, or (Parts D and E only) high-dose steroids (defined as 
prednisone 10 mg/day or its equivalent) within 30 days of receiving study drug (14 days for 
oral medications). Subjects on stable doses of bisphosphonates or receptor activator of 
nuclear factor kappa-B ligand (RANK-L) agents are permitted to enroll. Low-dose steroids, 
luteinizing hormone-releasing hormone, aromatase inhibitors (eg, anastrozole), at doses that 
have been stable for t30 days are permitted for subjects with CRPC;
6. History of severe allergic or anaphylactic reactions to previous mAb therapy;
7. Prior treatment with maytansinoid-containing drug conjugates (eg, Kadcyla [T-DM1]);
8. Subjects with a previously documented absence of thiol-S-purine methyltransferase activity; 
9. Unresolved acute toxicity NCI CTCAE v4.03 Grade >1 (or baseline, whichever is greater) 
from prior anticancer therapy. Alopecia and other nonacute toxicities are acceptable;
10. History of malignancy that is active within the previous 2 years except for localized cancers 
that are not related to the current cancer being treated, are considered to have been cured and 
in the opinion of the Investigator, present a low risk for recurrence, including basal or 
squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the prostate, 
cervix or breast;
11. Currently receiving anticoagulation therapy with warfarin;
12. The subject has undergone major surgery (requiring general anesthesia) within 3 months 
prior to dosing. Subjects who have undergone major surgery within this time period may be 
enrolled, after consultation with the Medical Monitor;
13. Subjects who have received a live vaccine within 28 days prior to the planned first dose of 
CX-2009 (examples include, but are not limited to, the following: measles, mumps, rubella, 
chicken pox/zoster, yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine);
14. Participating in an ongoing clinical study involving treatment with medications, radiation, or 
surgery;


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15. Women who are pregnant or breast feeding; or
16. Subjects who are >20.0% below their ideal body weight, as determined using the formula in 
Appendix F.
4.3
Additional Exclusion Criteria for Parts D1, D2, E1, and E2
17. History of myocarditis regardless of the cause;
18. History of intolerance to prior ICI therapy defined as the need to discontinue treatment due to 
an irAE;
19. History of any syndrome or medical condition that requires treatment with systemic steroids 
 mg daily prednisone equivalents) or immunosuppressive medications. However, 
subjects who require brief courses of steroids (eg, as prophylaxis for IV contrast or for 
treatment of an allergic reaction) may be eligible with Sponsor approval. Inhaled or topical 
steroids are permitted;
20. History of allogeneic tissue/solid organ transplant, stem cell transplant, or bone marrow 
transplant.
21. For HR-positive/HER2-negative BC, subjects must have not received prior PD-1 or PD-L1 
inhibitors.
4.4
Withdrawal Criteria
Subject MUST discontinue the study drug for any of the following reasons:
•
The subject experiences clinically significant or confirmed (RECIST) disease progression (or 
irRECIST in Parts D1, D2, E1, and E2), unless the subject experiences clinical benefit (as 
assessed by the Investigator); treatment beyond progression is permitted following 
consultation with the Medical Monitor or designee; however, the subject should be 
monitored and if continued progression occurs as defined by irRECIST, the subject must be 
withdrawn from the study drug;
•
The subject is unwilling or unable to adhere to the Module;
•
The subject withdraws consent or is lost to follow-up;
•
The subject experiences an intercurrent illness that prevents further administration of study 
drug;
•
The subject requires new/other anticancer treatment;
•
The subject experiences an AE related to study drug which precludes further administration 
of the study drug;
•
The subject experiences a prolonged treatment delay (as defined in Section 5.5.4);
•
The subject becomes pregnant, either prior to the first dose of study drug or at any time 
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•
In the Investigator’s judgment, the subject should discontinue treatment;
•
Death of the subject; or
•
The Sponsor terminates the study.
Subjects who discontinue study drug administration for reasons other than TRAEs may be 
replaced to ensure the minimum number of subjects required for DLT evaluation is enrolled. 
Subjects who have enrolled in the study and have withdrawn prior to receiving the first dose will 
be designated as screen failures. The reason for subject withdrawal must be documented in the 
electronic case report form (eCRF).


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5
STUDY TREATMENTS
5.1
Treatment Groups
Subjects will be treated with CX-2009 as monotherapy or with CX-2009 in combination with 
CX-072. Table 4 provides an overview of the eligible tumor types and enrollment numbers for 
each part.
5.2
Rationale for Dosing
5.2.1
CX-2009 as Monotherapy
5.2.1.1
Every 14-day Dosing Regimen
The rationale for the every 14-day dosing regimen is based on both modeling results and 
observed preliminary clinical data as described below. A targeted concentration range of 90 to 
190 nM for CX-2009 was derived upon both (1) observed tumor growth inhibition data in a 
mouse xenograft model, and (2) a quantitative systems pharmacology (QSP) model that was used 
to scale these results from mouse to human. The QSP model captures known mechanisms of 
Probody therapeutic receptor binding, cleavage, elimination, tissue and tumor biodistribution,
and receptor and receptor-drug complex endocytosis (Desnoyers 2013). The targeted 
concentration range reflects a range of assumed tumor interstitial to plasma ratios from the 
literature (Baxter 1995). Preliminary population PK (POPPK) and exposure-response analyses 
have been conducted using available data from study CTMX-M-2009-001. Preliminary 
exploratory exposure-safety analyses as of October 2019 were examined for possible correlations 
between selected TEAEs, including ocular toxicity, and maximal plasma concentration (Cmax), 
minimal plasma concentration (Cmin), and area under the concentration-time curve (AUC) for 
intact CX-2009, free DM4 and DM4 Me, and total CX-2009-conjugated DM4. Overall, p-values 
were the lowest for the intact CX-2009 exposure metrics. For ocular toxicity of Grade 3 and 
higher, there were statistically significant relationships (p<0.05) for intact AUC, intact Cmax, and 
intact Cmin. These results suggest that relative to the every 21-day dosing regimen, an every
14-day dosing regimen may permit a greater fraction of subjects to remain above the 90 nM 
targeted Cmin with a lower dose of CX-2009, possibly reducing the fraction of subjects who 
experience Cmax-related TEAEs.
The highest dose level tested in this clinical study for CX-2009 was 10 mg/kg administered 
every 21 days, which successfully cleared the DLT evaluation period. The every 14-day dosing 
regimen (which will be further tested in Parts C1 and C2) equivalent of 10 mg/kg administered 
every 21 days is approximately 7 mg/kg. In order to provide an additional margin of safety 
coverage for Part C1, the starting dose was 6 mg/kg, AIBW administered every 14 days. 
Six subjects were enrolled in this cohort. There were 3 DLTs in 2 of 5 evaluable subjects (a
Grade 3 neuropathy in one and Grade 3 AST/ALT elevations in another). The SRC reviewed the 
data and recommended that subjects currently on 6mg/kg every 14-day dosing regimen be dose 


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reduced to 4 mg/kg every 14-day dosing regimen, this is the next planned dose for evaluation in 
Part C1.
5.2.1.2
Every 21-day Dosing Regimen
Selection of the starting dose of 0.25 mg/kg CX-2009 every 21 days is based on nonclinical 
safety data on CX-2009 as well as nonclinical and clinical experience with other 
DM4-conjugated antibodies. Initially selected dose levels for Part A in the original Module were 
based on publicly available data for antibodies conjugated to DM4. Dose levels being 
implemented a subsequent amendment were based on a subsequently conducted analysis using 
available toxicology, pharmacology, and the QSP analysis outlined in Section 5.2.1.1.
The monotherapy every 21-day RP2D of 7 mg/kg administered every 21 days has been selected 
for Part B based upon observed clinical data and POPPK simulations. In the every 21-day dosing 
regimen, doses up to 10mg/kg were given without a protocol-defined DLT. However, there was 
a difference noted in the incidence of Grade 3 or higher keratitis at doses above 7 mg/kg 
administered every 21 days versus lower doses. As of the 28 October 2019 data cut date,
observed clinical safety data suggest Grade 3 or greater ocular toxicity was reported more 
frequently at dose levels of 8 mg/kg administered every 21 days and above. There was 1 report 
of Grade 3 ocular toxicity at a doses of 5 mg/kg administered every 21 days (there were no 
Grade 4 ocular toxicities at any dose of 7 mg/kg administered every 21 days or lower) and 
9 reports of Grade 3/4 ocular toxicity at doses of 8 mg/kg administered every 21 days and above 
(6mg/kg administered every 14 days from Part C1 was included in this group). Evidence of 
clinical activity was also observed at doses of 4 mg/kg administered every 21 days or higher. At 
GRVHVRIPJNJRIsubjects treated, the ORR was approximately 8% (all uPR) in a heavily 
pretreated population. The POPPK simulations suggested that relative to the 8 mg/kg every 
21-day dose level, the next greatest fraction of subjects was expected to surpass the targeted 
90 nM Cmin at the 7 mg/kg every 21-day dose level.
5.2.2
CX-2009 + CX-072 as Combination Therapy Every 14 Days, Dose 
Escalation/De-escalation (Part D1) and Expansion (Part D2)
5.2.2.1
CX-072 Dose – Parts D1 and D2
A fixed dose of 800 mg CX-072 every 14 days (equivalent to the 10 mg/kg every 14 days
weight-based dose) is proposed for combination with CX-2009 in Part D of study 
CTMX-M-2009-001. The 800 mg CX-072 every 14-day dose is the RP2D for CX-072 
monotherapy in study CTMX-M-072-001, and subjects currently being enrolled in Parts A2 and 
D of that study are receiving 10 mg/kg CX-072 every 14 days (equivalent to the 800 mg CX-072 
every 14 days fixed dose) as monotherapy. Published exposure-response information for the 
PD-L1 inhibitor atezolizumab (Stroh 2017) as well as the totality of available nonclinical and 
preliminary clinical data from study CTMX-M-072-001 were leveraged to support the 800 mg 
every 14-day fixed dose monotherapy regimen. A targeted Cmin for CX-072 was established 


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based upon an assumed required PD-L1 receptor occupancy (RO) for efficacy for atezolizumab 
(Deng 2016) as well as on results from a QSP model that was used to incorporate the effect of 
Probody properties on the Cmin required for this RO in the tumor for CX-072. Preliminary data 
from study CTMX-M-072-001 suggest that ADAs have been observed in subjects receiving 
CX-072, and that a fraction of those receiving <10 mg/kg CX-072 every 14 days have not 
maintained the targeted Cmin despite repeat dosing. Subjects receiving 10 mg/kg CX-072 every 
14 days have maintained the targeted Cmin regardless of ADA status. Because at high 
concentrations CX-072 can bind to its target even when the mask is intact, 10 mg/kg CX-072, the 
minimum dose at which the targeted Cmin was maintained, was selected as the every 14-day dose.
A subsequent model-based evaluation did not suggest there would be a clinically meaningful 
change in exposure following the fixed dose of 800 mg CX-072 every 14 days (equivalent to the 
10 mg/kg every 14-day weight-based dose) for investigation as the monotherapy RP2D in study 
CTMX-M-072-001. Clinical safety data for CX-072 and CX-2009 further suggest that 10 mg/kg 
CX-072 every 14 days is well tolerated as monotherapy with a manageable toxicity profile, and 
that there would be non-overlapping toxicities for CX-072 and CX-2009. Accordingly, the 
CX-072 800 mg every 14-day monotherapy RP2D is proposed as the single dose level and 
schedule for combination with CX-2009 in Part D of study CTMX-M-2009-001.
5.2.2.2
CX-2009 Dosing – Parts D1 and D2
CX-2009 is planned to be administered in combination with CX-072 800 mg every 14 days in 
Parts D1 and D2 of study CTMX-M-2009-001. To match the every 14-day dosing schedule of 
CX-072, CX-2009 is likewise planned to be dosed every 14 days. The starting dose for CX-2009
will be set at the every 14-day monotherapy RP2D as determined in Part C1. Lower starting
doses may be used based on emerging safety data and in consultation with the SRC.
5.2.3
CX-2009 + CX-072 as Combination Therapy Every 21 Days, Dose Escalation 
(Part E1) and Expansion (Part E2)
5.2.3.1
CX-072 Dose – Parts E1 and E2
A fixed dose of 1200 mg CX-072 administered every 21 days, which is equivalent to the 800 mg 
every 14-day dose, is planned for combination with CX-2009 in Parts E1 and E2 of study 
CTMX-M-2009-001.
5.2.3.2
CX-2009 Dosing – Parts E1 and E2
CX-2009 is planned to be administered in combination with CX-072 1200 mg every 21 days in 
Parts E1 and E2 of study CTMX-M-2009-001. To match the every 21-day dosing schedule of 
CX-072, CX-2009 is likewise planned to be dosed every 21 days. The starting dose of CX-2009
when administered with 1200 mg CX-072 every 21 days in Part E1 of study CTMX-M-2009-001 
is to be the CX-2009 every 21-day monotherapy RP2D of 7 mg/kg.


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5.3
Randomization and Blinding
This is an open-label study. No blinding is needed.
5.4
Breaking the Blind
This is an open-label study. No blinding is needed.
5.5
Drug Supplies and Administration
5.5.1
Formulation and Packaging
CX-2009
CX-2009 will be supplied as a lyophilized powder (cake) in 25 mg vials to be reconstituted with 
5 mL of sterile water for injection (WFI) to a final concentration of 5.0 mg/mL. The label for 
CX-2009 will include standard product information. It will also include: CAUTION: New Drug 
– Limited by Federal (or United States) Law to Investigational Use. For Clinical Trial Use Only. 
Return all unused study medication.
CX-072
CX-072 drug product is currently being supplied as a sterile solution for IV administration. 
CX-072 is supplied in a 10 mL volume, and each vial contains 100 mg of CX-072 formulated 
with suitable compendial excipients. Upon regulatory approval, the CX-072 drug product is 
planned to be supplied as a lyophilized powder (cake) in single-use vials for reconstitution with 
sterile WFI before IV administration. The stability of the drug product is monitored according to 
the International Council for Harmonisation (ICH) Guidelines. The period of use of CX-072 drug 
product will be managed based on the evaluation of real time stability data.
5.5.2
Study Drug Preparation and Dispensing
Complete study-specific preparation and dispensing instructions for CX-2009 and CX-072 are 
described in their respective Pharmacy Manuals.
5.5.3
Study Drug Administration
Study drugs include CX-2009 and CX-072.
Study drugs will be administered on an outpatient basis, with inpatient admission as needed for 
any treatment or monitoring outside of clinic hours or for management of significant acute 
toxicity. See Section 5.5.3.1 for management of IRRs.
All doses will be administered through an IV line containing a sterile, nonpyrogenic, low protein 
binding in-line filter (pore size of 0.2 m) and administered as an IV infusion controlled by a 
volumetric pump.


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Do not co-administer other drugs through the same IV line during the study drug infusion. Study 
drugs should be administered under the supervision of a physician or other study personnel 
experienced in the use of IV agents.
When CX-2009 and CX-072 are administered on the same day, CX-072 is to be administered 
first, followed by a saline flush, followed by the CX-2009 infusion. CX-2009 is to be infused no 
sooner than 30 minutes after completion of the CX-072 infusion.
Additional information on study drug administration can be found in the Pharmacy Manual.
CX-2009
CX-2009 will be administered as an IV infusion over 90 (r10) minutes with careful monitoring 
of IRRs. Following completion of the infusion, flush with an adequate amount of normal saline 
for infusion.
The SRC can modify the infusion rate for any dose if a dGrade 2 IRR occurs or if it is deemed to 
improve safe administration of CX-2009. If a tGrade 3 IRR occurs, this Module may be 
amended.
Do not administer CX-2009 as IV push or bolus injection.
CX-072
800 mg and 1200 mg CX-072 are to be infused over 60 (r10) minutes. Following completion of 
the infusion, flush with an adequate amount of normal saline for infusion.
5.5.3.1
Management of IRRs
Subjects should not receive any premedication prior to infusions, unless it is determined during 
the course of the study (by the SRC/Sponsor) that the occurrence of IRRs warrants routine 
prophylactic treatment (which might include paracetamol/acetaminophen, histamine antagonists, 
and/or corticosteroids).
Individual subjects who do experience a tGrade 2 IRR may receive premedication prior to 
subsequent treatment cycles after review with the Medical Monitor.
For allergic (hypersensitivity) reactions occurring during or after study drug (CX-2009 or 
CX-072) administration, follow the guidelines in Table 7.


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Table 7.
Management of Allergic Reactions
Grade of Allergic Reaction
Treatment
Grade 1: Transient flushing or rash, drug 
fever <38qC (<100.4qF)
Remain at bedside and monitor subject until recovery from 
symptoms.
Grade 2: Intervention or infusion 
interruption indicated; responds promptly to 
symptomatic treatment (eg, antihistamines, 
NSAIDs, narcotics); prophylactic 
medications indicated for d24 hours
Stop the study drug infusion, begin an IV infusion of normal 
saline and treat the subject as follows:
• Administer diphenhydramine 50 mg IV (or equivalent) and/or 
paracetamol/acetaminophen 325-1000 mg PO; remain at 
bedside and monitor subject until resolution of symptoms.
Corticosteroid therapy may also be administered as 
appropriate.
• If the infusion is interrupted, then restart the infusion at 50% of 
the original infusion rate when symptoms resolve; if no further 
complications ensue after 30 minutes, the rate may be 
increased to 100% of the original infusion rate.
• Monitor subject closely. If symptoms recur then the infusion 
should be discontinued and no further study drug will be 
administered at that visit. Administer diphenhydramine 50 mg 
IV and remain at bedside and monitor the subject until 
resolution of symptoms.
Premedication (diphenhydramine and 
paracetamol/acetaminophen) may be given prior to subsequent 
treatment cycles after review with the Medical Monitor.
Grade 3: Prolonged (eg, >6 hours, not 
rapidly responsive to symptomatic 
medication and/or brief interruption of 
infusion); recurrence of symptoms following 
initial improvement; hospitalization 
indicated for clinical sequelae (eg, renal 
impairment, pulmonary infiltrates)
Immediately discontinue infusion of study drug. Begin an IV 
infusion of normal saline, and treat the subject as follows:
• Recommend bronchodilators, epinephrine 0.2-1 mg of a 
1:1000 solution for subcutaneous administration or 
0.1-0.25 mg of a 1:10,000 solution injected slowly for IV 
administration, and/or diphenhydramine 50 mg IV with 
methylprednisolone 100 mg IV (or equivalent), as needed. 
• Subject should be monitored until the Investigator is 
comfortable that the symptoms will not recur.
• Study drug will be permanently discontinued unless 
continuation of therapy is believed to provide potential clinical 
benefit and no other reasonable alternatives exist, then 
re-challenge may be pursued at the discretion of the 
Investigator after consultation with the Medical Monitor.
• Investigators should follow their institutional guidelines for the 
treatment of anaphylaxis.
Grade 4: Life-threatening consequences; 
urgent intervention indicated.
Follow treatment for Grade 3 allergic reaction and monitor 
subject until recovery from symptoms. Study treatment will be 
permanently discontinued.
IV = intravenous; NSAID = nonsteroidal anti-inflammatory drug; PO = per os, oral.
During an IRR, vital signs will be obtained every 2 to 5 minutes until stable. In the case of 
late-occurring hypersensitivity symptoms (eg, appearance of a localized or generalized pruritus 
within 1 week after treatment), symptomatic treatment may be given (eg, oral antihistamine or 
corticosteroids).


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5.5.3.2
Ocular Toxicity
All subjects enrolled in this study must adhere to the following impactful safety measures for the 
duration of CX-2009 exposure and 21 days after the last dose of CX-2009:
•
Avoiding use of corrective contact lenses and switch to corrective glasses throughout the 
subject’s time of participation in the study. Bandage contact lenses may be considered if 
prescribed by the treating ophthalmologist;
•
Wearing ultraviolet A/ultraviolet B sunglasses whenever outdoors, even for short periods of 
time;
•
Using preservative-free artificial tear eye drops for lubrication 3 times daily, starting at least 
1 hour after the use of medicated eye drops; and 
•
All prophylactic measures for the eye during and post-infusion of CX-2009 listed below.
The following protective measures are required for all subjects to potentially reduce the exposure 
of the corneal limbal stem cells/transient amplifying cells to CX-2009 during and post-infusion:
1. Topical vasoconstrictor eye drops will be administered to both eyes, starting on the day of the 
infusion, 1 hour prior to each infusion of CX-2009. Brimonidine tartrate ophthalmic solution 
0.025% (in the United States) should be administered to both eyes every 6 to 8 hours for 
3 days, and brimonidine tartrate ophthalmic solution 0.2% (in Europe) should be 
administered to both eyes every 12 hours for 3 days, starting 1 hour prior to each infusion of 
CX-2009. If brimonidine tartrate ophthalmic solution is not available, tetrahydrozoline eye 
drops 0.05%, or naphazoline eye drops 0.025% may be used. If none of these agents are 
available or are not medically appropriate, suitable alternatives may be considered by the 
treating ophthalmologist, provided approval is granted by the Medical Monitor.
Vasoconstrictor eye drops may be continued for longer if instructed by the treating 
ophthalmologist;
2. A cool compress will be applied to the eyes at the time of the infusion and continued for at 
least 2 hours and as much as tolerated on the day of the infusion; and
3. Topical steroid drops (such as prednisolone acetate eye drops, 1.0% or its equivalent), will be 
instilled in both eyes at least 30 minutes prior to CX-2009 infusion, and continued 4 times a 
day for 7 days. In addition, subjects may elect to use a topical ophthalmic steroid ointment at 
bedtime for 7 nights, starting the day of each CX-2009 infusion. In place of steroid ointment, 
a subject may consider artificial tears ointment or simply use artificial tears before bedtime. 
Treatment with topical steroid eye drops and the optional ointment may be continued longer 
if instructed by the treating ophthalmologist.
Subjects should contact the oncology team as soon as any ocular symptoms are experienced 
(eg, blurred vision), which will prompt an ophthalmology evaluation. The oncology team may 
consider initiating treatment with prolonged therapy with steroid eye drops, unless there is 


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suspicion of infectious conjunctivitis. The Medical Monitor should be informed if ocular 
symptoms necessitating ophthalmology evaluation are observed.
If ocular toxicity occurs, see Section 5.5.4.1.
5.5.4
Treatment Delays, Dose Modification, and Missed Doses
Treatment or visit delays for public holidays, weather conditions, or other unforeseeable 
circumstances (including toxicity considered unrelated to study treatment) do not constitute a 
protocol violation. However, delayed visits should be completed at the first available 
opportunity. 
There must be a minimum of 21 days (Parts A, A2, B, E1, and E2) or 14 days (Parts C1, C2, D1, 
and D2) between study drug infusions (a window of r2 days may occur). In exceptional 
circumstances, an infusion may be delayed for up to 7 days. Infusions that cannot be 
administered in that timeframe will be considered a missed dose, and the subject’s next planned 
dose should be 42 days (every 21-day dosing regimen; Parts A, A2, B, E1, and E2) or 28 days 
(every 14-day dosing regimen; Parts C1, C2, D1, and D2) after the last administered dose. A 
subject will be considered to have experienced a prolonged treatment delay and study drug will 
be discontinued if the subject misses 2 consecutive infusions, except as provided for in 
Section 5.5.4.1 and Section 5.5.4.2.
Subjects benefitting from treatment may be allowed longer treatment delays after discussion with 
the Medical Monitor. Subjects should be assessed for resolution of toxicity (eg, by scheduled 
physical examination, laboratory testing, etc.) at a frequency deemed by the Investigator to be 
appropriate for the specific clinical situation.
5.5.4.1
Dose Management for CX-2009
Dose delay or permanent discontinuation of CX-2009 may be required as dictated in Table 8 and 
Table 9.
Note: Where CX-2009 and CX-072 are administered in combination (Parts D1, D2, E1, and E2), 
if, in the opinion of the Investigator, a toxicity is considered to be due solely to one component 
of the study treatment (ie, CX-2009 or CX-072) and the dose of that component is delayed, 
modified, or permanently discontinued in accordance with the guidelines in the Module, the 
other component may be administered if there is no contraindication.


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Table 8.
CX-2009 Dose Modifications for Select Adverse Events
Adverse Event
Grade 1
Grade 2
Grade 3
Grade 4
Anemia
No action
No action
Hold until recovery to 
dGrade 2 with transfusion;
re-challenge at same dose. a
Hold until recovery to 
dGrade 2 with transfusion;
re-challenge at same dose a if 
Grade 4 recurs, permanently 
discontinue CX-2009.
Neutropenia
No action
No action
Hold until recovery to 
dGrade 2; re-challenge at 
same dose. a
Hold and consider supportive 
measures until recovery to 
dGrade 2; re-challenge at 
same dose. a
Thrombocytopenia
No action
No action
PLT 
25,000/mm3– <50,000 mm3
PLT <25,000/mm3
Hold until platelet count 
recovers to dGrade 1 and then 
treat at same dose level.
Hold until platelet count 
recovers to dGrade 1 and 
then treat at same dose level.
Increased serum 
transaminases 
(AST/ALT)
Note: Corticosteroids 
may be considered for 
the management of 
liver enzyme 
elevations
No action
No action
Hold until AST/ALT recovers 
to dGrade 2 and then treat at 
same dose level.
Permanently discontinue 
CX-2009.
Hyperbilirubinemia
No action
Hold until total 
bilirubin recovers 
to dGrade 1 and 
then treat at same 
dose level.
Hold until total bilirubin 
recovers to dGrade 1 and then 
treat at same dose level.
Permanently discontinue 
CX-2009.
Peripheral neuropathy 
(sensory motor)
No action
For new or 
worsening 
Grade 2
neuropathy, hold 
CX-2009 until 
neuropathy 
improves to 
Grade 1 or 
baseline.
For new or worsening Grade 3 
neuropathy, hold CX-2009
until neuropathy improves to 
Grade 1 or baseline. Restart at 
same dose level. a Please note 
that a dose reduction may be 
considered in consultation 
with the Medical Monitor. 
Discontinue treatment 
permanently if no 
improvement within 2 weeks.
For new or worsening 
Grade 4 neuropathy, hold 
CX-2009 until neuropathy 
improves to Grade 1 or 
baseline. Please note that a 
dose reduction may be 
considered; consultation with 
the Medical Monitor is 
required. Discontinue 
treatment permanently if no 
improvement within 2 weeks.
Life-threatening or 
Grade 4 reaction
NA
NA
NA
Permanently discontinue 
CX-2009.
a Please note that dose reduction may be considered following consultation with the Medical Monitor.
ALT = alanine aminotransferase; AST = aspartate aminotransferase; NA = not applicable; PLT = platelet count.
Neutropenia. Neutropenia should be managed by dosing delays. The dose of CX-2009 should 
be held for Grade 3 or Grade 4 neutropenia until resolution to baseline or dGrade 2. Growth 
factor support should be considered for subsequent cycles in subjects who experience Grade 3 or 
Grade 4 neutropenia. In subjects with recurrent Grade 4 neutropenia despite the use of growth 
factors, discontinuation of CX-2009 should be considered. 
The dose of CX-2009 should be held for Grade 3 AEs judged by the Investigator to be 
treatment-related that are not listed in Table 8 until resolution to baseline or Grade 0.


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In the event of a major surgery (any intervention requiring more than local anesthesia), stop 
dosing; resume dosing after consultation with the Medical Monitor.
Ocular Toxicity. In addition to the scheduled examinations, subjects who report new ocular 
symptoms will undergo repeat examinations as clinically indicated as well as prior to infusion 
every other cycle (every 42 days for Parts A, A2, B, E1, and E2; every 56 days for Parts C1, C2, 
D1, and D2). Management of treatment-emergent ocular disorders should include corticosteroid 
eye drops and/or other measures as indicated by the treating ophthalmologist. For 
steroid-refractory symptoms, the treating ophthalmologist may recommend other modalities, 
including higher dose topical corticosteroids, topical cyclosporine, or lifitegrast. These agents are 
not mandatory but may be used based on the treating ophthalmologist’s recommendation. 
Management of treatment-emergent ocular disorders is described in detail in Table 9.
Table 9.
Management of Treatment-emergent Ocular Disorders
Category
Management
Guidelines for 
CX-2009 Dose Modifications
Category A:
Symptomatic but no 
impact on ADL
•Complete eye examination as outlined in 
Appendix B;
•Ensure protective measures for the eye are being 
utilized as described in Section 5.5.3.2;
•Monitor for worsening symptoms; and
•Subjects should have weekly ocular assessments 
until the symptoms resolve to baseline or are 
deemed to be irreversible by the Investigator.
Continue CX-2009 dosing.
Category B:
Symptomatic impact on 
ADL including preparing 
meals, shopping for 
groceries or clothes, using 
the telephone, or 
managing money
•Complete eye examination as outlined in 
Appendix B. Repeat complete examination as 
clinically indicated;
•Ensure protective measures for the eye are being 
utilized as described in Section 5.5.3.2;
•Monitor for worsening symptoms;
•Treatment with corticosteroid eye drops and/or 
topical ophthalmic steroid ointment at bedtime 
and/or other measures as indicated by the treating 
ophthalmologist; and 
•Subjects should have weekly ocular assessments
until the symptoms resolve to baseline or are 
deemed to be irreversible by the Investigator.
Hold CX-2009 dosing until there is no 
longer a symptomatic impact on ADL.
If a dose is needed to be held due to 
symptomatic impact on ADL for 
<2 weeks, resume dosing at the same 
dose level.
If a dose is needed to be held due to 
symptomatic impact on ADL for 
> 2 weeks, dose reduction is required.
Category C:
Symptomatic impact on 
self-care ADL (including 
bathing, dressing and 
undressing, feeding self, 
using the toilet, taking 
medications, and not 
bedridden)
•Complete eye examination as outlined in 
Appendix B. Repeat complete examination as 
clinically indicated;
•Ensure protective measures for the eye are being 
utilized as described in Section 5.5.3.2;
•Treatment with corticosteroid eye drops and/or 
topical ophthalmic steroid ointment at bedtime 
and/or other measures as indicated by the treating 
ophthalmologist; and
•Subjects should have weekly ocular assessments 
until the symptoms resolve to baseline or are 
deemed to be irreversible by the Investigator.
Hold CX-2009 dosing until there is no 
longer a symptomatic impact on ADL. 
Dose reduction is required.
A permanent discontinuation 
consideration should be made with the 
Investigator, ophthalmologist, and after 
discussion with the Medical Monitor.
ADL = activities of daily living.


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Dose Reduction. Dose reduction steps are outlined in Table 8 and Table 9. In cases where 
Tables 8 or 9 do not indicate a dose reduction, a dose reduction may be approved with 
consultation of the Medical Monitor. There cannot be more than 42 days (every 21-day dosing
regimen; Parts A, A2, B, E1, and E2) or 28 days (every 14-day dosing regimen; Parts C1, C2,
D1, and D2) between dosing unless approved by the Medical Monitor (see Section 5.5.4).
In Parts A, A2, B, D1, D2, E1, and E2, as a first step, CX-2009 dose may be reduced to a dose 
level 1 mg/kg below the assigned starting dose. Should the AE reoccur after the first dose 
reduction, a further dose reduction (by another 1 mg/kg reduction) can be attempted if clinically 
beneficial and following consultation with the Medical Monitor. No subsequent dose escalation 
of CX-2009 will be authorized for subjects who have had a dose reduction for safety reasons.
In Parts C1 and C2, as a first step, CX-2009 dose may be reduced to a dose level below the 
assigned starting dose. Should the AE reoccur after the first dose reduction, a further dose 
reduction (by another 1 mg/kg reduction) can be attempted if clinically beneficial and following 
consultation with the Medical Monitor. No subsequent dose escalation of CX-2009 will be 
authorized for subjects who have had a dose reduction for safety reasons.
5.5.4.2
Dose Management for CX-072
The following guidance is for dose modification of CX-072. Delays or permanent 
discontinuation of CX-072 may be required as outlined in Table 10 and Section 5.5.10. Dose 
reduction of CX-072 is not permitted. Guidance is adapted from American Society of Clinical 
Oncology Clinical Practice Guidelines (Brahmer 2018), which should be referenced for 
additional detail and information when assessing and managing AEs that are considered to be 
potentially immune related.
If, in the opinion of the Investigator, a toxicity is considered to be due solely to one component 
of the study treatment (ie, CX-2009 or CX-072) and the dose of that component is delayed, 
modified, or permanently discontinued in accordance with the guidelines in the Module, the 
other component may be administered if there is no contraindication.
Additional recommendations for interventions of irAEs depending on severity of the event are 
provided in Section 5.5.5.


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Table 10.
CX-072 Dose Modifications for Select Adverse Events
Page 1 of 2
Adverse Event
Grade 1
Grade 2
Grade 3
Grade 4
Skin toxicities including 
dermatitis, 
Stevens-Johnson 
syndrome, or toxic 
epidermal necrolysis
See also Section 5.5.5.11
No action; G1 does 
not apply to severe 
cutaneous toxicities 
(eg, Stevens-Johnson 
syndrome, toxic 
epidermal necrolysis, 
etc.).
Hold until recovery 
to dG1 or baseline.
Hold until recovery 
to dG1 or baseline. 
Consult with a 
dermatologist.
Permanently 
discontinue CX-072.
Colitis a
See also Section 5.5.5.1
No action; may 
consider holding 
study treatment and 
resuming if toxicity 
does not exceed G1.
Hold until recovery 
to dG1.
Hold until recovery 
to dG1.
Permanently 
discontinue CX-072.
Increased serum 
transaminases 
(AST/ALT) or total 
bilirubin
See also Section 5.5.5.2
No action; monitor 
laboratory values 1 to 
2 times per week.
Hold until recovery 
to dG1 or baseline on 
SUHGQLVRQH mg 
per day.
Permanently 
discontinue CX-072.
Permanently 
discontinue CX-072.
Pneumonitis
See also Section 5.5.5.3
No action.
Hold until recovery 
to dG1.
Permanently 
discontinue CX-072.
Permanently 
discontinue CX-072.
Hypothyroidism or 
hyperthyroidism
See also Section 5.5.5.4
No action.
Hold until recovery 
to dG1 or baseline
(with hormone 
replacement for 
hypothyroidism).
Hold until recovery 
to dG1 or baseline 
(with hormone 
replacement for 
hypothyroidism).
Permanently 
discontinue study 
treatment.
Adrenal insufficiency
See also Section 5.5.5.6
Consider holding 
until subject is 
stabilized.
Hold until recovery 
to dG1 or baseline 
with hormone 
replacement.
Hold until recovery 
to dG1 or baseline 
with hormone 
replacement.
Refer to 
endocrinologist. Hold 
CX 072 and contact 
Sponsor Medical 
Monitor to discuss 
discontinuation of 
study.
Hypophysitis
See also Section 5.5.5.8
Consider holding 
CX-072 until 
stabilized on 
replacement therapy.
Hold until recovery 
to dG1 or baseline 
with hormone 
replacement.
Hold until recovery 
to dG1 or baseline 
with hormone 
replacement.
Refer to 
endocrinologist. Hold 
CX 072 and contact 
Sponsor Medical 
Monitor to discuss 
discontinuation of 
study.
Type 1 diabetes
See also Section 5.5.5.7
NA; G1 does not 
apply to subjects with 
evidence of Type 1 
diabetes or ketosis.
Hold until recovery 
to dG1 or baseline.
Urgent endocrine 
consultation for all 
subjects. 
Initiate insulin 
therapy for all 
subjects.
Hold until recovery 
to dG1 or baseline. 
Urgent endocrine 
consultation for all 
subjects. 
Initiate insulin 
therapy for all 
subjects.
Refer to 
endocrinologist. Hold 
CX 072 and contact 
Sponsor Medical 
Monitor to discuss 
discontinuation of 
study.
Creatinine
No action; consider
holding treatment 
pending workup.
Hold until recovery 
to dG1 or baseline. 
Consult nephrology.
Hold until recovery 
to dG1 or baseline. 
Permanently 
discontinue for Grade 
3 nephritis.
Permanently 
discontinue CX-072.


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Table 10.
CX-072 Dose Modifications for Select Adverse Events
Page 2 of 2
Adverse Event
Grade 1
Grade 2
Grade 3
Grade 4
Pancreatitis (as diagnosed 
by biopsy, clinical 
examination, or 
symptoms); clinically 
asymptomatic elevation in 
amylase and lipase are not 
sufficient
Monitor for 
symptoms and 
laboratory 
abnormalities.
Hold until recovery 
to dG1 or baseline.
Hold until recovery 
to dG1 or baseline.
Permanently 
discontinue CX-072.
Myocarditis
See also Section 5.5.5.5
NA
For any clinical suspicion, refer to cardiologist 
for workup, diagnosis, and treatment. Obtain 
cardiac MRI. Hold CX-072 and contact 
Sponsor Medical Monitor to discuss 
discontinuation of study.
Encephalitis or 
meningoencephalitis See 
also Section 5.5.5.10
For any clinical suspicion, refer to neurologist for workup, diagnosis, and treatment. Hold 
CX-072 and contact Sponsor Medical Monitor to discuss discontinuation of CX-072.
Ocular inflammatory 
toxicity (eg, uveitis, 
conjunctivitis, orbital 
inflammation, episcleritis)
See also Section 5.5.5.9
Refer to 
ophthalmology.
Hold until recovery 
to dG1 or baseline.
Refer to 
ophthalmology.
Permanently 
discontinue CX-072.
Refer to 
ophthalmology.
Permanently 
discontinue CX-072.
Refer to 
ophthalmology.
Guillain-Barre syndrome 
or myasthenia gravis
For any clinical suspicion, refer to neurologist for workup, diagnosis, and treatment. Hold study 
treatment and contact Sponsor Medical Monitor to discuss discontinuation of study treatment. 
For any confirmed diagnosis of any grade, treatment must be discontinued.
Other immune-related 
adverse reactions (except 
those listed above) 
See also Section 5.5.5.12
No action.
No action; consider 
holding treatment 
depending on organs 
involved.
Hold and contact 
Sponsor Medical 
Monitor to discuss 
treatment, which may 
include administration 
of systemic steroids.
Hold and contact 
Sponsor Medical 
Monitor to discuss
treatment, which 
may include 
administration of 
systemic steroids.
Grade 3 adverse reactions 
(except those listed 
above)
NA
NA
Hold until recovery to 
dG1 or baseline.
NA
Life-threatening or 
Grade 4 adverse reactions 
(except those listed 
above)
NA
NA
NA
Permanently 
discontinue CX-072.
a Based on CTCAE for diarrhea as most often used clinically.
ALT = alanine aminotransferase; AST = aspartate aminotransferase; CTCAE = Common Terminology Criteria for Adverse 
Event; G1 = Grade 1; MRI = magnetic resonance tomography; NA = not applicable; PD-L1 = programmed death ligand 1.
Resume CX-072 LQSDWLHQWVZKRVHDGYHUVHUHDFWLRQVUHFRYHUWR*UDGHRUEDVHOLQHDWWKH
discretion of the Investigator unless otherwise stated in Table 10 and/or Section 5.5.5.12.
5.5.5
CX-072 Management of Immune-related Toxicity
All AEs should be monitored and managed according to standard of care. Refer to “Management 
of irAEs in patients treated with ICI therapy: American Society of Clinical Oncology clinical 
practice guideline” (Brahmer 2018) for specific guidance. For any suspected immune-related 
toxicities, other causes should be excluded and treated appropriately per standard of care.


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5.5.5.1
Immune-related Colitis
Counsel subject to inform the Investigator of any abdominal pain, nausea, cramping, blood or 
mucus in stool or changes in bowel habits, fever, abdominal distention, obstipation, or 
constipation. 
For Grade 1 events, consider temporary withholding CX-072 to confirm toxicity does not exceed 
Grade 1. Withhold CX-072 for Grade 2 or 3 immune-related colitis. For moderate (Grade 2) 
colitis administer corticosteroids, unless diarrhea is transient, starting with initial dose of 
1 mg/kg per day prednisone or equivalent. Gastroenterology should be consulted. For severe 
(Grade 3) or life-threatening (Grade 4) colitis, administer corticosteroids at a dose of 1 to 
2 mg/kg per day prednisone equivalents (for Grade 3) or 1 to 2 mg/kg per day 
methylprednisolone equivalents (for Grade 4) followed by corticosteroid taper. If Grade 3
V\PSWRPVSHUVLVWIRUWR days or recur after improvement, consider administering IV 
corticosteroid or noncorticosteroid (eg, infliximab). Consider colonoscopy/GI endoscopy in 
cases where subjects have been on immunosuppression and may be at risk for opportunistic 
infections as an independent cause for diarrhea (ie, cytomegalovirus [CMV] colitis) and for those 
who are anti-71)RUFRUWLFRVWHURLGUHIUDFWRU\:KHQV\PSWRPVLPSURYHWR*UDGHWDper 
corticosteroids over at least 4 to 6 weeks before resuming treatment, although resuming 
treatment while on low-dose corticosteroid may also be an option after an evaluation of the risks 
and benefits. Permanently discontinue CX-072 for Grade 4 or recurrent colitis upon restarting 
CX-072.
5.5.5.2
Immune-related Hepatitis
Monitor subjects for abnormal liver tests prior to and periodically during treatment with CX-072.
(This management guideline may be altered for subjects with evidence of liver metastases who 
had screening elevation of transaminases; optimal subject management in these subjects should 
be discussed with the Medical Monitor).
For Grade 1 elevations of AST, ALT, and/or total bilirubin, monitor laboratory values 1 to 
2 times per week. For Grade 2 elevations of AST, ALT, and/or total bilirubin (AST or ALT 
>3.0 WR5 × ULN and/or total bilirubin >WR3 × ULN), hold CX-072, recheck laboratory 
values and increase frequency of monitoring to every 3 days; administer corticosteroid 0.5 to 
1 mg/kg per day (prednisone or equivalent) if the abnormal elevation persists with significant 
clinical symptoms in 3 to 5 days. CX-072 may be resumed only when symptoms improve to 
*UDGHDQGFRUWLFRVWHURLGGRVHLVPJSHUGD\7DSHURYHUDWOHDVW month. Subjects 
should be advised to stop unnecessary medications and any known hepatotoxic drugs. For 
Grade 3 hepatitis (AST or ALT 5-20 × ULN and/or total bilirubin 3-10 × ULN), immediately 
start corticosteroid 1 to 2 mg/kg per day methylprednisolone or equivalent. Increase frequency of 
monitoring to every 1 to 2 days. If corticosteroid refractory or no improvement after 3 days, 
consider mycophenolate mofetil or azathioprine (if using azathioprine, test for thiopurine 


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methyltransferase deficiency). Measure laboratory parameters at least daily or every other day; 
consider inpatient monitoring for subjects with AST/ALT >8 × ULN and/or elevated total 
bilirubin 3 × ULN. Corticosteroid taper can be attempted around 4 to 6 weeks; re-escalate if 
needed; optimal duration unclear. For Grade 4 hepatitis, administer 2 mg/kg per day 
methylprednisolone equivalents and follow guidance for Grade 3. 
Permanently discontinue CX-072 for Grade 3 or Grade 4 immune-related hepatitis (for subjects 
with elevation of liver transaminases at screening, discontinuation of CX-072 should be 
discussed with the Medical Monitor).
Infliximab might not be the most appropriate treatment option in the situation of immune-related 
hepatitis given the potential risk of idiosyncratic liver failure, mycophenolate mofetil may be 
considered.
5.5.5.3
Immune-related Pneumonitis
Monitor subjects for signs and symptoms of pneumonitis. Subjects with Grade 1 pneumonitis 
should be monitored weekly and CX-072 should be held if there is radiographic evidence of 
pneumonitis progression. CX-072 may be resumed with radiographic evidence of improvement 
or resolution. If no improvement, should treat as Grade 2. Subjects should be monitored weekly. 
For Grade 2 pneumonitis, recommend treatment with corticosteroids at a dose of 1 to 2 mg/kg 
per day prednisone equivalents, followed by a corticosteroid taper by 5 to 10 mg per week over 
4 to 6 weeks. Consider bronchoscopy with bronchoalveolar lavage and empirical antibiotics. 
Monitor every 3 days. If no improvement after 48 to 72 hours of prednisone, treat as Grade 3. 
For Grade 3 pneumonitis, empirical antibiotics and corticosteroids (prednisolone IV 1 to 2 mg/kg 
per day) should be administered. If no improvement after 48 hours, may add 5 mg/kg infliximab 
or mycophenolate mofetil IV 1 g twice a day or IV immunoglobulin for 5 days or 
cyclophosphamide; taper corticosteroids over 4 to 6 weeks. Pulmonary and infectious disease 
consults should be sought if necessary. Subjects should be hospitalized for further management.
Withhold CX-072 for Grade 2 immune-related pneumonitis and permanently discontinue 
CX-072 for Grade 3 or 4 or recurrent pneumonitis upon restarting CX-072.
5.5.5.4
Immune-related Hypothyroidism and Hyperthyroidism
Monitor thyroid function prior to and periodically (test for thyroid-stimulating hormone [TSH] 
and free thyroxine (FT4) every 4 to 6 weeks and as clinically indicated) during treatment with 
CX-072.
For Grade 1 hypothyroidism, CX-072 may be continued with close follow-up and monitoring of 
TSH and FT4. For Grade 2 hypothyroidism, CX-072 should be withheld, thyroid hormone 
supplementation prescribed for symptomatic subjects with any degree of TSH elevation or in 
asymptomatic subjects with TSH levels that persist >10 mIU/L (measured 4 weeks apart). 
Endocrinology consult should be considered. For Grade 3 hypothyroidism, CX-072 should be 


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held, supplementation prescribed, and endocrinology consult obtained. For Grade 4 
hypothyroidism, treatment should be permanently discontinued, supplementation prescribed, and 
endocrinology consult obtained. May admit for IV therapy if signs of myxedema (bradycardia, 
hypothermia). 
For Grade 1 hyperthyroidism, may continue CX-072 with close follow-up and monitoring of 
TSH and FT4 every 2 to 3 weeks until it is clear whether there will be persistent 
hyperthyroidism. For Grade 2 hyperthyroidism, CX-072 should be held, medical management 
initiated, and endocrinology consultation considered. For persistent hyperthyroidism (>6 weeks) 
or clinical suspicion, a workup for Graves’ Disease should be initiated. For Grade 3
hyperthyroidism, CX-072 should be held, medical management initiated, and endocrinology 
consulted. For Grade 4 hyperthyroidism, treatment should be permanently discontinued, 
supplementation prescribed, and endocrinology consult obtained. For severe symptoms or 
concern for thyroid storm, should hospitalize subject and initiate prednisone 1 to 2 mg/kg per day 
or equivalent tapered over 1 to 2 weeks. May also use saturated solution of potassium iodide or 
thionamide (methimazole or propylthiouracil). 
Consider that thyroiditis is transient and within weeks resolves to primary hypothyroidism or 
normal. Graves’ disease is generally persistent and due to increased thyroid hormone production 
that can be treated with antithyroid medical therapy.
5.5.5.5
Immune-related Myocarditis
Monitor subjects for myocarditis prior to and periodically during treatment with CX-072. For all 
grades of myocarditis, permanent CX-072 discontinuation should be discussed. Cardiology
should be consulted, cardiac magnetic resonance imaging obtained, and high-dose corticosteroids 
should be administered (1 to 2 mg/kg of prednisone initiated rapidly (oral or IV depending on 
symptoms). In subjects without an immediate response to high-dose corticosteroids, consider 
cardiac transplant rejection doses of corticosteroids (methylprednisolone 1 g every day) and the 
addition of either mycophenolate, infliximab, or anti-thymocyte globulin. Permanently 
discontinue CX-072 for any >Grade 2 myocarditis.
5.5.5.6
Immune-related Adrenal Insufficiency
Monitor for signs and symptoms of adrenal insufficiency. Evaluate adrenocorticotropic hormone 
(ACTH) (a.m.), cortisol level (a.m.), and metabolic panel (sodium, potassium, carbon dioxide, 
and glucose). Consider ACTH stimulation test for indeterminate results. For evidence of primary 
adrenal insufficiency (high ACTH, low cortisol), evaluate for a precipitating cause of crisis, such 
as infection, and perform an adrenal computed tomography scan for metastasis/hemorrhage. For 
Grade 1 adrenal insufficiency, CX-072 may be held until subject is stabilized on replacement 
hormone. Withhold CX-072 for Grade 2, Grade 3, or Grade 4 events until the subject is 
stabilized on replacement hormones. Endocrinology should be consulted for all grades of adrenal 
insufficiency including for recommendations on replacement and stress dose steroid therapy.


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5.5.5.7
Immune-related Type 1 Diabetes
Monitor subjects for hyperglycemia or other signs and symptoms of new or worsening diabetes 
mellitus, including measuring glucose at baseline. Laboratory evaluation in suspected Type 1 
diabetes should include testing for ketosis in urine and an assessment of the anion gap on a 
metabolic panel. Withhold CX-072 for Grade 2, Grade 3, or Grade 4 events, perform urgent 
endocrine consultation for all subjects, and initiate insulin therapy for all subjects. Hold CX-072
until glucose control is obtained on therapy with reduction of toxicity to dGrade 1.
5.5.5.8
Immune-related Hypophysitis 
Monitor for signs and symptoms of hypophysitis. Evaluate ACTH (a.m.), cortisol (a.m.), TSH, 
FT4, and electrolytes at baseline and determine whether hypophysitis or adrenal insufficiency is 
to be ruled out. Evaluate additional hormones (eg, follicle-stimulating hormone [FSH],
luteinizing hormone [LH], testosterone, estrogen) as clinically indicated. Consider brain imaging 
(pituitary/sellar cuts) if clinically indicated. Consider holding CX-072 for Grade 1 events until 
subject is stabilized on replacement therapy. Withhold CX-072 for Grade 2, Grade 3, or Grade 4 
events until the subject is stabilized on replacement hormones. Endocrinology should be 
consulted. Be aware of the need to start corticosteroids first when planning hormone replacement 
therapy for multiple deficiencies.
5.5.5.9
Immune-related Uveitis and Other Ocular Inflammatory Toxicities
Counsel subject to inform the Investigator of any vision changes, eyelid swelling, proptosis, or 
pain. Refer to ophthalmology for all subjects (within 1 week for all subjects for Grade 1 events; 
urgent referral for Grade >1 events). Withhold CX-072 for Grade 2 events until after 
ophthalmology consult. Treatment for Grade 1 uveitis includes artificial tears. Treatment for 
>Grade 1 events includes topical and systemic corticosteroids. Resume CX-072 after return to 
dGrade 1. Permanently discontinue CX-072 for Grade 3 and Grade 4 uveitis or episcleritis. 
Blepharitis does not have a formal grading system. Treatment includes warm compresses and 
lubrication drops. CX-072 may continue unless the event is persistent and/or serious.
5.5.5.10
Immune-related Encephalitis or Meningoencephalitis
Monitor for changes in neurologic function. Withhold CX-072 for new onset or moderate to
severe neurologic symptoms and evaluate to rule out infectious or other causes of neurologic 
deterioration. Withhold CX-072 for Grade 1, Grade 2, or Grade 3 events and consult with 
neurology. Consider concurrent IV acyclovir until polymerase chain reaction results are obtained 
and negative, and treatment with methylprednisolone and additional treatment (eg, IV 
immunoglobulin, rituximab as recommended by neurology consultation). Permanently 
discontinue CX-072 for confirmed diagnosis of autoimmune encephalopathy.


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5.5.5.11
Immune-related Skin Toxicity
For rash and inflammatory dermatitis, Grade 1 toxicities should be treated with emollients and/or 
mild-moderate potency topical corticosteroids. Counsel subjects to avoid skin irritants and sun 
exposure. For Grade 2 toxicities, consider initiating prednisone (or equivalent) at 1 mg/kg, 
tapering over at least 4 weeks. In addition, treat with topical emollients, oral antihistamines, and 
topical medium to high potency corticosteroids. For Grade 3 toxicities, initiate 1 to 2 mg/kg 
(methyl)prednisolone (or equivalent), tapering over at least 4 weeks and treat also with topical 
emollients, oral antihistamines, and topical medium-high potency corticosteroids. Consult with 
dermatologist. For Grade 4 toxicities, treat with systemic corticosteroids IV 
(methyl)prednisolone (or equivalent) 1 to 2 mg/kg with slow tapering when the toxicity resolves. 
Admit subject immediately with urgent consult by dermatology. 
For bullous dermatoses and severe cutaneous adverse reactions refer to Brahmer et al for 
additional guidance (Brahmer 2018). Refer to dermatology for blisters that are not explained by 
infectious/transient other causes (eg, herpes simplex, herpes zoster infections, pressure/friction 
bullae). When symptomatic bullae or erosions are observed on the skin or mucosal surfaces, the 
cutaneous irAE is, by definition, considered at least Grade 2.
5.5.5.12
Other Immune-related Adverse Reactions
For any suspected irAEs, exclude other causes. Based on the severity of the adverse reaction, 
withhold CX-072, administer high-dose corticosteroids, and/or if appropriate, initiate hormone 
UHSODFHPHQWWKHUDS\8SRQLPSURYHPHQWWR*UDGHLQLWLDWHFRUWLFRVWHURLGWDSHUDQGFRQWLQXH
to taper over at least 1 month. Consider restarting CX-072 after completion of corticosteroid 
taper based on the severity of the event. 
Refinement of the recommended treatment of TRAEs will be made as the study progresses.
If any of the immune-related symptoms worsen or do not improve with the guidelines above, 
tumor necrosis fDFWRUDOSKD71)ĮLQKLELWRUVPD\EHDGPLQLVWHUHGDWWKHGLVFUHWLRQRIWKH
Investigator.
5.5.6
Adverse Event Recovery Monitoring 
If recovery of an AE is not seen within 4 weeks, the Investigator must review the subject with 
the Medical Monitor to determine if the subject should be permanently withdrawn from the study 
drug or a further period of waiting for resolution is warranted.
5.5.7
Treatment Compliance
CX-2009 and CX-072 will be administered only by study personnel by IV infusion at the study 
site. The infusion date and start and stop times will be recorded in the source documents and 
eCRF.


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5.5.8
Storage and Accountability
It is the responsibility of the Investigator to ensure that the study drug is stored as specified by 
the Sponsor and in accordance with applicable regulatory requirements. Drug accountability 
details are provided in the Core (Appendix A).
CX-2009
CX-2009 vials must be stored at a temperature of 2°C to 8°C. Vials should be stored in the 
carton. Once CX-2009 has been prepared for administration, the total storage time (combination 
of refrigeration and room temperature) is not to exceed 24 hours. Stability data for CX-2009
supports 8 hours at room temperature/under room light and 24 hours at 2°C to 8°C in the 
refrigerator following dilution and transfer to the IV bag. Care must be taken to assure sterility of 
the prepared solution as the product does not contain any anti-microbial preservative or 
bacteriostatic agent. No incompatibilities between CX-2009 and polyolefin bags have been 
observed. Do not freeze.
CX-072
CX-072 vials must be stored upright at a temperature of 2°C to 8°C (36°F to 46°F). Vials should 
be stored in the carton. Once CX-072 has been prepared for administration, the total storage time 
(combination of refrigeration and room temperature) is not to exceed 24 hours. Stability data for 
CX-072 supports 8 hours at room temperature/under room light and 24 hours at 2°C to 8°C in the 
refrigerator following dilution and transfer to the IV bag. Care must be taken to assure sterility of 
the prepared solution as the product does not contain any anti-microbial preservative or 
bacteriostatic agent. No incompatibilities between CX-072 and polyolefin bags have been 
observed. Vials should be stored in the original carton until time of use. Do not freeze.
5.5.8.1
Product Complaints
A product complaint is any perceived deficiency related to physical, chemical or biological 
properties, or the labeling, or packaging of a product. 
If the solution is cloudy, discolored, or contains extraneous particular matter, quarantine the 
product and report the deficiency on a Product Complaint Form as described in the Pharmacy 
Manual. A Complaint Investigator will follow-up to obtain additional information and provide 
instructions on how to return the product.
Record the product return on the Drug Accountability Log to ensure complete tracking of drug 
supply.
5.5.9
Discontinuation of CX-2009 for Adverse Events
Subjects with Grade 4 AEs requiring permanent discontinuation of CX-2009 as described in 
Table 8 and Table 9 must be discontinued. Subjects who fail to resolve AEs as described in 


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Section 5.5.6 must be discontinued unless a discussion between the Investigator and Medical 
Monitor documents that a further period of waiting for resolution is warranted.
Where CX-2009 and CX-072 are administered in combination (Parts D1, D2, E1, and E2), if, in 
the opinion of the Investigator, a toxicity is considered to be due solely to one component of the 
study treatment (ie, CX-2009 or CX-072) and the dose of that component is delayed, modified, 
or permanently discontinued in accordance with the guidelines in the Module, the other 
component may be administered if there is no contraindication.
5.5.10
Discontinuation of CX-072 for Adverse Events
Permanent discontinuation of CX-072 may be required as outlined in Table 10.
Where CX-2009 and CX-072 are administered in combination (Parts D1, D2, E1, and E2), if in 
the opinion of the Investigator a toxicity is considered to be due solely to one component of the
study treatment (ie, CX-2009 or CX-072), and the dose of that component is delayed, modified, 
or permanently discontinued in accordance with the guidelines in the Module, the other 
component may be administered if there is no contraindication.
CX-072 should be permanently discontinued for either of the following:
•
,QDELOLW\WRUHGXFHFRUWLFRVWHURLGGRVHWRPJRISUHGQLVRQHRUHTXLYDOHQWSHUGD\ZLWKLQ
12 weeks of initiation of corticosteroid
•
Persistent Grade 2 or 3 TRAEs WKDWGRQRWUHFRYHUWR*UDGH or baseline or resolve within 
12 weeks after the last dose of CX-072
For adverse reactions that do not recover within 4 weeks, the Investigator must contact the 
Sponsor Medical Monitor to determine if the subject should be permanently withdrawn from 
CX-072 or if a longer period of waiting for resolution is warranted.
5.5.11
Additional Guidelines
Refinement of the recommended management of TRAEs will be made as the study progresses.
5.6
Prior and Concomitant Medications and/or Procedures
5.6.1
Excluded Medications and/or Procedures
Medications taken within 30 days before the administration of study drug and concomitant 
medications and therapies administered during the study will be recorded on the relevant eCRF. 
1. The use of herbal remedies, other marketed anticancer chemo/immunotherapy/hormonal 
drugs, or investigational drugs is not permitted.
2. New chemotherapy, hormonal, radiation, or immunotherapy are not permitted during the 
screening or treatment periods.


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3. Palliative therapies (eg, focal radiotherapy for pain, thoracentesis or paracentesis for comfort) 
is permitted after consultation with the Medical Monitor. A subject whose brain metastases 
are progressing on head imaging and who requires radiotherapy will be withdrawn from the 
study drug.
4. The use of live vaccines is prohibited 28 days prior to the planned first dose of CX-2009, 
while on study drug, and for 90 days after the last dose of CX-2009. The use of any killed or 
attenuated vaccines for the prevention of influenza is permitted. The use of other killed or 
attenuated vaccines for the prevention of infectious diseases may be permitted on a 
case-by-case basis after discussion with the Medical Monitor. Any vaccinations administered 
during the study must be documented in the subject’s medical records and in the eCRF.
Concomitant medications taken by the subject while in the treatment period should be recorded 
in the eCRF. After EOT, only concomitant medications administered for irAEs occurring within 
90 days after last dose will be recorded. Once a subject enters the Follow-Up Period, only new 
therapies for the treatment of their cancer should be recorded in the eCRF.
5.6.2
Restricted Medications and/or Procedures
Any other anticancer treatment such as chemotherapy, immunotherapy, biochemotherapy, 
radiotherapy, investigative therapy, or high-dose steroids (except to treat TEAEs) are prohibited 
during and within 30 days prior to receiving study drug. Luteinizing hormone-releasing hormone 
agonists are permitted for pre-menopausal women. For subjects with CRPC, overlapping 
anti-androgen therapy with CX-2009 is allowed. Anticoagulation therapy with warfarin is also 
prohibited.
Standard supportive medications may be used in accordance with institutional guidelines and 
Investigator discretion. These may include hematopoietic growth factors to treat neutropenia or 
thrombocytopenia in accordance with ASCO guidelines, transfusions, bone-targeted agents 
(bisphosphonates and/or RANK-L agents), antiemetics, antidiarrheals, and glucocorticoids,
including treatment of an immune-related toxicity or short courses to treat asthma, chronic 
obstructive pulmonary disease, etc.
Continuation of standard of care medications (particularly hormonal related therapies for prostate 
carcinoma) that the subject has been on for the previous 30 days at stable doses are allowed.
See Section 5.7 for guidance on the avoidance of concomitant medications that are sensitive 
substrates of CYP3A or are CYP3A substrates with a narrow therapeutic index.
For Subjects Receiving CX-072 (Parts D1, D2, E1, and E2). Inhaled or intranasal 
corticosteroids (with minimal systemic absorption) may be continued if the subject is on a stable 
dose. Nonabsorbed intra-articular steroid injections will be permitted. Systemic corticosteroids 
required for the control of IRRs or irAEs must be tapered and must be at nonimmunosuppressive 
doses (<10 mg/day of prednisone or equivalent) prior to the next study drug administration. The 


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use of steroids as prophylactic treatment for subjects with allergies to diagnostic imaging 
contrast dyes will be permitted.
5.7
Advice to Investigators Related to Potential Drug Interactions
In vitro metabolism studies and studies in mice suggest that DM4 is predominantly metabolized 
by thiol S-methyltransferase to form another highly active metabolite DM4-Me, which is further 
metabolized into the less active sulfoxide-methyl-DM4 and eliminated in the bile. Because 
DM4-Me has been shown to be primarily metabolized by CYP3A4 in human hepatic 
microsomes, its exposure could potentially be increased in the presence of strong CYP3A 
inhibitors. If concomitant medication with a CYP3A inhibitor cannot be avoided, monitor for 
risk of increased toxicity. Drinking greater than 1 serving (250 mL) of grapefruit juice per day 
should be avoided. Appendix G provides examples of CYP3A inhibitors. An in vitro study 
evaluating the potential for CYP inhibition demonstrated that DM4 and DM4 Me are not direct 
inhibitors of the 7 CYP isoforms evaluated, however DM4 showed time-dependent inhibition of 
CYP3A4 and DM4-Me showed weak time-dependent inhibition of CYP2C8 and CYP2C9.
Treatment of subjects with concomitant medications that are sensitive substrates of CYP3A or 
are CYP3A substrates with a narrow therapeutic index should be avoided (see Appendix H for 
examples).
6
EFFICACY ASSESSMENTS
The primary criteria for defining evidence of anticancer activity and also for management of 
subject care will be a clinical response as defined by RECIST (Version 1.1). Management of 
subjects in Parts D1, D2, E1, and E2 may also take into consideration tumor response assessed 
by irRECIST. Efficacy in this study will be explored in subjects on the basis of:
•
ORR by the RECIST (Version 1.1);
•
TTR;
•
DOR;
•
PFS; and
•
OS.
Efficacy in subjects treated with the combination CX-2009 plus CX-072 (Parts D1, D2, E1, and 
E2) will be explored additionally on the basis of:
•
ORR by irRECIST as defined in the Core (Appendix A)
Please refer to the Core for a description of the efficacy assessments.


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7
PHARMACOKINETIC, IMMUNOGENICITY, AND EXPLORATORY 
BIOMARKER ASSESSMENTS
7.1
Pharmacokinetic Assessments
Concentration versus time data will be tabulated and plotted for the individual and mean 
CX-2009 (total and intact), CX-2009-conjugated DM4 and free DM4, and DM4-Me analytes and 
for total and intact CX-072 moieties. PK parameters, including AUC, Cmax, Cmin, clearance, and 
volume of distribution at steady state, will be calculated for CX-2009 (total and intact), DM4
(conjugated and free), and DM4-Me analytes as appropriate and as data allow. Additional 
parameters such as terminal elimination half-life and accumulation may be calculated, and dose 
proportionality will be assessed for subjects with sufficient data. Estimates for these parameters 
will be tabulated and summarized (eg, mean, standard deviation, and coefficient of variation).
CX-072 (total and intact moieties) Cmax and Cmin will be tabulated individually and summarized 
using descriptive statistics (eg, mean, standard deviation, and coefficient of variation).  
Additional exploratory model-based PK analyses may be conducted and the results of these 
analyses may be reported in a document separate from the clinical study report.
Plasma samples will be drawn from a site other than the infusion site (ie, contralateral arm) on 
days of infusion at the times indicated in Appendix B.
If the infusion was interrupted, the reason for interruption will also be documented in the eCRF 
and a sample will be collected at the end of the infusion and at the times specified after the end 
of infusion.
7.2
Exploratory Biomarkers
Probody therapeutics differ from unmodified mAbs by the recombinant addition of a prodomain 
at the amino-terminus of the light chain, which blocks the antibody binding to its target antigen 
and can be removed by tumor-associated protease activity. In this way, CX-2009 and CX-072 are
expected to be activated in tumors and bind to their targets, CD166 and PD-L1 respectively, but 
to be relatively inactive outside of the TME.
The overall goal of the biomarker portion of CTMX-M-2009-001 is to explore A) Probody 
therapeutic mechanistic proof of concept, and B) potential predictive markers associated with the
clinical activity of CX-2009 alone or in combination with CX-072.
This information will help to further build the translational program for the development of 
CX-2009 and CX-072.
The presence of activated proteases capable of activating the Probody therapeutics in the human 
TME will be assessed using a semi-quantitative zymographic assay that combines ex vivo 
incubation of the Probody therapeutic probe in sections of biopsy and capillary electrophoresis 
analysis to measure the intact and cleaved Probody therapeutics. A similar capillary 


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electrophoretic method will be used to measure the Probody therapeutic activation in plasma and 
on-treatment tumor biopsies following administration of CX-2009 alone or in combination with 
CX-072. The expression of the target, CD166, will be evaluated using a Clinical Laboratory 
Improvement Amendments of 1998-validated IHC assay.
Exploratory studies will include the evaluation of:
•
Probody therapeutic activation in tumors and in blood;
•
The potential link between tumor markers, such as the target of CX-2009 (ie, CD166), the 
target of CX-072 (ie, PD-L1) and the biological activity of CX-2009 alone or in combination 
with CX-072;
•
The potential link between exploratory biomarkers in blood and the biological activity of 
CX-2009 alone or in combination with CX-072; and
•
The presence of activated proteases in the human TME capable of removing the peptide 
mask and thereby activating the Probody therapeutic.
7.3
Exploratory Biomarkers Collection
In order to address the above objectives, tissue samples will be collected throughout the course 
of the study. 
For Parts A and C1, pretreatment and on-treatment tumor biopsies will be optional. For the 
subjects who consent, tumor biopsies will be collected during the Screening Period (baseline) 
and 3 to 5 days after the first dose of CX-2009, provided that the tumor is accessible and a 
biopsy is deemed safe by the treating physician.
For Part A2, tumor biopsies (fixed and frozen) are required 3 to 5 days after the first dose of 
CX-2009, provided that the tumor is accessible and a biopsy is deemed safe by the treating 
physician.
For Parts B and C2, consent to pretreatment and on-treatment tumor biopsies will be mandatory 
in at least 7 subjects for each tumor type. For these subjects, tumor biopsies (fixed and frozen) 
will be collected during the Screening Period (baseline) and 3 to 5 days after the first dose of 
CX-2009, provided that the tumor is accessible and a biopsy is deemed safe by the treating 
physician.
For Parts D1, D2, E1, and E2, on-treatment tumor biopsies will be optional. For the subjects 
who consent, tumor biopsies will be collected 3 to 5 days after the third dose, provided that the 
tumor is accessible and a biopsy is deemed safe by the treating physician.


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8
SAFETY ASSESSMENTS
8.1
Adverse Events
An AE is defined as any untoward medical occurrence in a clinical investigation subject 
administered a pharmaceutical product, which does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and/or unintended sign (including 
an abnormal laboratory finding), symptom, or disease temporally associated with the use of an 
investigational medicinal product, whether or not related to the investigational medicinal 
product. All AEs, including observed or volunteered problems, complaints, or symptoms, are to 
be recorded on the appropriate eCRF.
Progressive disease in and of itself is not considered an AE or SAE. Progressive disease is an 
efficacy finding and should not be reported unless the progressive disease results in death during 
the reporting period (from date of signed informed consent to 30 days post last study treatment
administration). On-study deaths, reported as SAEs due to progressive disease and considered 
unrelated to study drug will be excluded from treatment-emergent AE analysis.
8.1.1
Suspected Adverse Reaction
A suspected adverse reaction is an AE for which there is a reasonable possibility that the study 
drug(s) caused the AE. For the purposes of Investigational New Drug safety reporting, 
“reasonable possibility” means there is evidence to suggest a causal relationship between the 
study drug(s) and the AE. Suspected adverse reaction implies a lesser degree of certainty about 
causality than adverse reaction, which means any AE caused by the study drug(s).
8.1.2
Life-Threatening Adverse Event or Life-Threatening Suspected Adverse Reaction
An AE or suspected adverse reaction is considered “life threatening” if, in the view of either the 
Investigator or Sponsor, its occurrence places the subject at immediate risk of death. It does not 
include an AE or suspected adverse reaction that, had it occurred in a more severe form, might 
have caused death.
8.1.3
Serious Adverse Event or Serious Suspected Adverse Reaction
An AE or suspected adverse reaction is considered “serious” if, in the view of either the 
Investigator or Sponsor, it results in any of the following outcomes:
•
Death
•
A life-threatening AE (see definition above)
•
Inpatient hospitalization or prolongation of existing hospitalization
•
A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions


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•
A congenital anomaly/birth defect 
•
Important medical events: Based on medical judgment, may jeopardize the subject or may 
require medical or surgical intervention to prevent one of the outcomes listed above
(eg, anaphylaxis, allergic bronchospasm requiring intensive treatment in an emergency room 
or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization).
8.1.4
Unexpected Adverse Event or Unexpected Suspected Adverse Reaction
An AE or suspected adverse reaction is considered “unexpected:” 
•
If it is not listed in the IB or is not listed at the specificity or severity that has been observed; 
or 
•
If an IB is not required or available, is not consistent with the risk information described in 
the general investigational plan or elsewhere in the current application, as amended. 
For example, under this definition, hepatic necrosis would be unexpected (by virtue of greater 
severity) if the IB referred only to elevated hepatic enzymes or hepatitis. Similarly, cerebral 
thromboembolism and cerebral vasculitis would be unexpected (by virtue of greater specificity) 
if the IB listed only cerebral vascular accidents. 
“Unexpected,” as used in this definition, also refers to AEs or suspected adverse reactions that 
are mentioned in the IB as occurring with a class of drugs or as anticipated from the 
pharmacological properties of the drug, but are not specifically mentioned as occurring with the 
particular drug under investigation. 
8.2
Adverse Event Classification
8.2.1
Relationship to Investigational Drug
The Investigator’s assessment of causality must be provided for all AEs (serious and 
non-serious). An Investigator’s causality assessment is the determination of whether there exists 
a reasonable possibility that the study drug caused or contributed to an AE. The relationship to 
study drug will be categorized as “Yes” or “No.”
8.2.2
Severity
The severity of an event describes the degree of impact upon the subject and/or the need for, and 
extent of, medical care necessary to treat the event.
AE grading will be defined by the NCI CTCAE v4.03. In the event that the NCI CTCAE v4.03
does not apply, the severity descriptions in Table 11 will be used to describe the maximum 
intensity of the AE.


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Table 11.
Adverse Event Severity
Grade
Description
Grade 1
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention 
not indicated
Grade 2
Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate 
instrumental activities of daily living. 
Grade 3
Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living
Grade 4
Life-threatening consequences; urgent intervention required
Grade 5
Death related to an adverse event
Source: https://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf. Accessed 19 November 
2019.
8.3
Exposure in Utero
The subject will be instructed to notify the Investigator if the subject or subject’s partner 
becomes pregnant during the study. The Investigator must notify the Sponsor or designee within 
24 hours via the Pregnancy Notification Form to meet the 24-hour reporting requirement. If it is 
not possible to report the pregnancy via the Pregnancy Notification Form, telephone or e-mail 
will be acceptable. The Investigator should obtain informed consent/assent from the subject or 
subject’s partner allowing the Investigator to obtain information regarding the pregnancy and its 
outcome. If the subject or subject’s partner provides informed consent/assent, the Investigator 
should follow the pregnancy until outcome. A final Pregnancy Notification Form should be 
completed when the outcome of the pregnancy is known.
Although not an AE per se, pregnancy in either a patient or the partner of a patient taking trial 
medication should be reported as an SAE to facilitate outcome monitoring by the Sponsor. 
Abortion, whether therapeutic or spontaneous, should always be classified as an SAE (as the 
Sponsor considers these to be medically significant), recorded on the eCRF, and expeditiously 
reported to the Sponsor as an SAE.
8.4
Monitoring of Adverse Event Data
Safety information in the study will be monitored on an ongoing basis by the Medical Monitor 
and Investigators and discussed at regular teleconferences. 
AEs occurring during the reporting period (up to and including 30 days after administration of 
the last dose of study drug for all AEs and up to and including 90 days after administration of the 
last dose of study drug for all irAEs related to CX-072) should be followed until resolution to 
baseline status, initiation of a new therapy, or stabilization.
Proper instruction will be provided to each site to ensure prompt reporting and communication 
between the Sponsor, Investigators, Food and Drug Administration (FDA) and other regulatory 
agencies regarding any DLTs or other AEs of interest.


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For SAEs, the Investigator has to complete the SAE Form electronically in the electronic data 
capture (EDC) system for the study with as much information as possible and submit it in the 
time frame described in Section 8.6. When new significant information is obtained as well as 
when the outcome of an event is known, the Investigator should record the information in the 
EDC system. If the subject was hospitalized, a copy of the discharge summary and any other 
relevant hospital records (eg, admission report, laboratory test results, etc.) should be included as 
part of the subject’s medical file. 
All AEs in which the relationship is considered “yes” to study drug and all SAEs will be 
followed until resolved or until a stable status has been achieved. The type of follow-up
(eg, phone, site visit, etc.) will be left to the discretion of the Investigator.
8.5
Documentation of Adverse Events by Investigator
Subjects will be evaluated and questioned generally to identify AEs during the course of the 
study. Any events occurring prior to administration of the first dose, will be recorded on the 
Medical History eCRF. SAEs will be recorded on the Adverse Event eCRF from informed
consent through 30 days following the last dose of CX-2009 and (for irAEs) through 90 days 
after administration of the last dose of CX-072. Events occurring after administration of the first 
dose of study drug will be recorded on the Adverse Event eCRF. AEs that occur up to and 
including 30 days after administration of the last dose of study drug must be reported in the EDC 
system.
All AEs spontaneously reported by the subject and/or in response to an open question from study 
personnel or revealed by observation, physical examination, or other diagnostic procedures will 
be recorded on the Adverse Event eCRF for that visit. Any clinically relevant deterioration in 
laboratory assessments or other clinical findings is considered an AE and must be recorded on 
the Adverse Event eCRF. In addition, an abnormal test finding will be classified as an AE if 1 or 
more of the following criteria are met:
•
The test finding is accompanied by clinical symptoms;
•
The test finding necessitates additional diagnostic evaluation(s) or medical/surgical 
intervention, including significant additional concomitant drug treatment or other therapy. 
Note: Simply repeating a test finding, in the absence of any of the other listed criteria does 
not constitute an AE;
•
The test finding leads to a change in study drug dosing or discontinuation of subject 
participation in the clinical research study; and
•
The test finding is considered clinically significant by the Investigator based on his/her 
medical judgment. If an abnormal laboratory result is recorded as an AE, then the 
corresponding laboratory value must be marked clinically significant in the database. 
Similarly, if an abnormal laboratory value is marked clinically significant in the database,
there should be a corresponding AE entered.


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Wherever possible, a specific disease or syndrome rather than individual associated signs and 
symptoms should be identified. However, if an observed or reported sign or symptom is not 
considered a component of a specific disease or syndrome by the Investigator, it should be 
recorded as a separate AE. Laboratory data are to be collected as stipulated in this Module.
Clinical syndromes associated with laboratory abnormalities are to be recorded as appropriate 
(eg, diabetes mellitus rather than hyperglycemia).
8.6
Notification About Serious Adverse Events and Suspected Unexpected Serious 
Adverse Reactions
Suspected unexpected serious adverse reactions (SUSARs) for CX-2009 and CX-072 will be 
distributed to the relevant regulatory authorities, independent ethics committees (IECs),
institutional review boards (IRBs), and sites participating in CX-2009 clinical studies. SUSARs 
for CX-072 will be distributed to the relevant regulatory authorities, ethics committees, IRBs,
and sites participating in the CX-072 clinical studies.
8.6.1
Investigator Reporting to Sponsor
All SAEs that occur during the course of the study must be reported to the Sponsor and Medpace 
Clinical Safety within 24 hours of the knowledge of the occurrence (this refers to any AE that 
meets any of the aforementioned serious criteria). In addition, all SAEs that occur up to and 
including 30 days following the last dose of CX-2009 and (for irAEs) through 90 days after 
administration of the last dose of CX-072 must be reported to the Sponsor within 1 working day 
from when the Investigator becomes aware of the SAE.
To report the SAE, the Investigator must record the SAE on the AE eCRF in the EDC system as 
well as any relevant eCRF forms (eg, drug dispensation eCRF, applicable laboratory eCRF).
When the AE eCRF is completed, Medpace Safety personnel will be notified electronically and 
will retrieve the form. If the event meets serious criteria and it is not possible to access the EDC 
system, send an e-mail to Medpace Safety at medpace-safetynotification@medpace.com or call 
the Medpace SAE hotline (phone number listed below), and fax the completed paper SAE Form 
to Medpace (fax number listed below) within 24 hours of awareness (see Table 12 for contact 
information). When the EDC system becomes available, the SAE information must be entered 
within 24 hours of the system becoming available.
Table 12.
Safety Contact Information: Medpace Clinical Safety
Medpace SAE Reporting Line – USA
Medpace SAE Reporting Line – Europe
Telephone
+1-800-730-5779, dial 3 or 
+1-513-579-9911, dial 3
+49 89 89 55 718 44
Fax
+1-866-336-5320 or 
+1-513-579-0444
+49 89 89 55 718 104
e-mail
medpace-safetynotification@medpace.com
medpace-safetynotification@medpace.com


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Investigators must report to the Sponsor any SAE, whether or not considered drug related, 
including those listed in the Module or IB. The report must include an assessment of causality. 
For all SAEs, the Investigator is obligated to obtain and provide information to the Sponsor in 
accordance with the timeframes for reporting specified above. In addition, an Investigator may 
be requested by the Sponsor to obtain specific additional follow-up information in an expedited 
fashion. This information may be more detailed than that captured on the SAE Form. In general, 
this will include a description of the AE in sufficient detail to allow for a complete medical 
assessment of the case and independent determination of possible causality. Information on other 
possible causes of the event, such as concomitant medications and illnesses must be provided. In 
the case of a subject death, a summary of available autopsy findings must be submitted as soon 
as possible to the Sponsor or its designee.
8.6.2
Serious Adverse Events Follow-Up
The Investigator must continue to follow the subject until the SAE has subsided or until the
condition becomes chronic in nature, stabilizes (in the case of persistent impairment), or the 
subject dies.
Within 24 hours of receipt of follow-up information, the Investigator must update the AE eCRF 
and any other relevant eCRFs for the study. If requested, the Investigator must submit any
supporting documentation (eg, subject discharge summary or autopsy reports) to Medpace 
Clinical Safety via fax or e-mail. If it is not possible to access the EDC system, refer to the 
procedures outlined above for initial reporting of SAEs.
8.6.3
Reporting to Regulatory Agencies and Central Institutional Review 
Board/Independent Ethics Committees
The Sponsor will report all relevant information about SUSARs that are fatal or life threatening 
as soon as possible to the FDA as applicable, applicable competent authorities in all the Member 
States concerned, and the Central IRB/IEC and in any case no later than 7 days after initial 
knowledge by the Sponsor of such a case. After the initial 7-day SUSAR report, a final 15-day 
SUSAR report will be submitted (ie, 8 days after the initial 7-day notification). Subsequently, 
follow-up for fatal or life-threatening SUSARs will be communications within 15 days. 
All other SUSARs will be reported to the FDA as applicable, applicable competent authorities, 
and the Central IRB/IEC as soon as possible but within a maximum of 15 days of first 
knowledge by the Sponsor.
The Sponsor will inform all Investigators as required with instructions to submit to local 
IRBs/IECs per local requirements.


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8.7
Rapid Notification of Adverse Events of Special Interest 
In addition to SAEs, the following AEs will be reported to the Sponsor or its designee within 
24 hours even if the nature of the AE is not deemed serious:
•
AEs that potentially meet DLT criteria,
•
tGrade 3 eye disorders (including blurred vision),
•
tGrade 2 infusion reactions whether or not the event is a DLT,
•
Any Grade 2 neurotoxicity,
•
Any potential Hy’s Law case (ie, ALT or AST >3 × ULN with concurrent total bilirubin 
>2 × ULN and ALP <2 × ULN, with lack of alternate etiology); and
For Parts D1, D2, E1, and E2: Any of the following irAEs defined as: AEs requiring the use of 
systemic corticosteroids within 30 days after the AE onset date with no clear alternate etiology, 
or requiring the use of systemic hormonal supplementation: 
•
Pneumonitis,
•
Colitis,
•
Hepatitis (including AST or ALT elevations >3 × ULN or bilirubin >1.5 × ULN),
•
Nephritis (including serum creatinine >1.5 × ULN),
•
Pancreatitis,
•
Motor and sensory neuropathy (including Guillain-Barré syndrome and myasthenia gravis),
•
Myocarditis, 
•
Encephalitis or meningoencephalitis,
•
Endocrinopathies (including but not limited to hypothyroidism, hyperthyroidism, 
hypophysitis, diabetes mellitus, and adrenal insufficiency),
•
Autoimmune ocular toxicities (eg, uveitis),
•
Skin reactions including Stevens-Johnson syndrome or toxic epidermal necrolysis, and
•
Diarrhea.
Please refer to Section 8.6 and the Core (Appendix A) for reporting SAEs, DLTs, and events of 
special interest. 


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8.8
Module-Specified Events
Subjects with advanced cancer enrolling in this study who have received prior treatment may 
have some degree of bone marrow suppression from prior therapy and/or laboratory 
abnormalities due to underlying disease status. Only changes in the grade of baseline laboratory 
values that require intervention (eg, transfusions, delay in study drug administration) should be 
reported as AEs.
Common AEs observed with other maytansinoid or MTI (eg, auristatin) ADCs may be expected 
for CX-2009. These include:
•
Blood and lymphatic system disorders: neutropenia, thrombocytopenia, and lymphopenia;
•
Nervous system disorders: peripheral neuropathy (sensory and motor) and paresthesia;
•
Eye disorders: blurred vision, dry eyes, and keratopathy (including corneal cyst, corneal 
disorder, corneal epithelial microcysts, keratitis, limbal stem cell deficiency, and punctate 
keratitis);
•
General disorders and administration site conditions: fatigue, pyrexia, pain, confusion, and 
headache;
•
Hepatotoxicity (including increases in AST or ALT);
•
Hypokalemia;
•
Hypomagnesemia;
•
Pulmonary disorders: interstitial lung disease;
•
Infections and infestations: upper respiratory tract infection;
•
Gastrointestinal disorders: nausea, diarrhea, abdominal pain, vomiting, decreased appetite, 
and constipation;
•
Skin and subcutaneous tissue disorders: rash and pruritus; and
•
Respiratory, thoracic, and mediastinal disorders: cough and dyspnea.
Common AEs (>15%) observed with the use of CX-072 (10 mg/kg administered every 21 days;
n=114) include:
•
Fatigue (34%)
•
Anemia (25%)
•
Decreased appetite (23%)
•
Diarrhea (22%)
•
Nausea (22%)
•
Increased AST (19%)
•
Vomiting (18%)
•
Cough (16%)
•
Dyspnea (16%)


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9
STATISTICAL CONSIDERATIONS
Part A, dose escalation with an every 21-day dosing regimen, of the study consists of an 
accelerated titration design, followed by a 3+3 design, and ending in a cohort using the mTPI-2
design. During dose escalation (3+3 design), the exact sample size will be determined by the 
observed safety profile, which will determine the number of subjects per cohort and the number 
of cohorts. 
Once the MTD is defined or the highest dose is tested (ie, 10 mg/kg, AIBW), up to 38 subjects 
can be enrolled at the MTD to refine dose selection using mTPI-2, a rule-based design similar to 
the 3+3 design that allows dose escalation/de-escalation. In November 2019, the selection of 
7 mg/kg as the MTD/RP2D was made based on factors including safety, efficacy, and PK/PD, by 
the Sponsor with input from the SRC.
Part B, with an every 21-day dosing regimen, is designed to provide a preliminary assessment of 
efficacy at the MTD/RP2D. Given the confirmed ORR seen to date in subjects with 
HR-positive/HER2-negative BC receiving monotherapy CX-2009 on the every 21-day schedule, 
a 2-stage enrollment design will no longer be incorporated. The SRC will continue to review 
on-going safety and efficacy data throughout the course of the clinical study. The sample size 
was selected to estimate the ORR. With 40 subjects treated, if 8 subjects have confirmed 
objective responses, the observed ORR will be 20% (90% CI: 10% - 33%); the lower bound of 
the 90% CI would therefore exclude an ORR of 10%.
Part C1, dose escalation/de-escalation using the mTPI-2 design with an every 14-day dosing 
regimen, will enroll up to 24 subjects (3 to 6 subjects at each dose level) for the purposes of 
MTD/RP2D decisions. 
Part C2, with an every 14-day dosing regimen, is designed to provide a preliminary assessment 
of clinical activity at the MTD/RP2D. Once the MTD/RP2D is defined in Part C1, expansion 
cohorts of up to 40 subjects in selected tumor types will be enrolled as described in Part B to 
evaluate the antitumor activity using the MTD/RP2D in Part C2. A 2-stage design may be 
incorporated into this cohort.
Part D1, dose escalation/de-escalation using the mTPI-2 design for CX-2009 with an every 
14-day dosing regimen in combination with CX-072, will enroll up to 24 subjects (3 to 6 subjects 
at each dose level) for the purposes of MTD/RP2D decisions. 
Part D2, dose expansion of CX-2009 plus CX-072 with an every 14-day dosing regimen, is 
designed to provide a preliminary assessment of clinical activity at the MTD/RP2D. Once the 
MTD/RP2D is defined in Part D1, expansion cohorts of 40 subjects in selected tumor types will 
be enrolled as described in Part B to evaluate the antitumor activity of CX-2009 plus CX-072. A
2-stage design may be incorporated into this cohort.


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Part E1, dose escalation using the mTPI-2 design for CX-2009 with an every 21-day dosing 
regimen in combination with CX-072, will enroll up to 24 subjects (3 to 6 subjects at each dose 
level) for the purposes of MTD/RP2D decisions. 
Part E2, dose expansion of CX-2009 plus CX-072 with an every 21-day dosing regimen, is 
designed to provide a preliminary assessment of clinical activity at the MTD/RP2D. Once the 
MTD/RP2D is defined in Part E1, expansion cohorts of 40 subjects in selected tumor types will 
be enrolled as described in Part B to evaluate the antitumor activity of CX-2009 plus CX-072. A
2-stage design may be incorporated into this cohort.
Enrollment within the expansions will be suspended if either of the following Safety Stopping 
Rules are met in the first 6 subjects enrolled in Parts B, C2, D2, and E2:
•
DLT rate is >30% within 21 days (Parts B and E2) or within 28 days (Parts C2 and D2) of 
the first dose of study drug
•
>20% of subjects have a treatment interruption or discontinuation within the first 6 weeks of 
the first dose of study drug or within 6 weeks of a single dose reduction step for subjects who 
experience events with their first dose of study drug
One of the major exploratory objectives aims at evaluating the relative Probody therapeutic
activation in the tumor versus blood across various indications. The relative degree of Probody 
therapeutic activation in the tumor versus blood is expected to be influenced by Probody 
therapeutic dose, protease activity, and tumor target (CD166) expression. The variable nature of 
the protease activity and target expression in the tumor between subjects is expected to lead to 
variation in relative Probody therapeutic activation. For Part A2, tumor biopsies are required 3 to 
5 days after the first dose of CX-2009. For the dose expansion (Part B), consent to pretreatment
and on-treatment tumor biopsies will be mandatory for at least 7 subjects for each tumor type.
Based on nonclinical data, the differential activation between tumor and blood has a mean of 
about 20.0% and a standard deviation of about 5.0%. For Part A2 with 6 subjects enrolled in a 
dose cohort, the 90.0% CI (based on t-distribution with 5 degrees of freedom) for the differential 
activation is (16.0%, 24.0%). For each of the expansion cohorts in Parts B and C2, the 90.0% CI
(based on t-distribution with 6 degrees of freedom) for the differential activation based on the 
best case scenario of 7 subjects is (16.3%, 23.7%), and based on the more likely scenario of 
4 subjects is (14.1%, 25.9%). In addition, the variability in protease activity between subjects 
might further reduce our ability to measure Probody therapeutic activation in the tumor. It is
anticipated that the requested tumor biopsies will provide reasonable estimates for this FIH 
study. If tumor biopsies are not mandatory, fewer subjects would be available for analysis, and 
the estimates would be less precise.


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9.1
Populations
For assessment of MTD/RP2D, the population will be based on subjects who are evaluable for 
DLT determination (a “DLT-evaluable” subject is defined as having received at least 1 dose of 
CX-2009 (or CX-2009 and CX-072) and completed the full DLT observation period (either 21 or 
28 days depending on the schedule) or a subject who has withdrawn from the study drug due to a 
drug-related toxicity. Subjects who are not DLT evaluable may be replaced in the cohort.
For assessment of efficacy (Parts B, C2, D2 and E2), subjects must have undergone at least 
1 on-study imaging assessment. Subjects who die prior to his/her first on-study scan will not be 
counted as evaluable for this assessment.
The efficacy evaluable group for Parts D2 and E2 will include only those subjects who are 
determined to be PD-L1 positive.    
9.2
Other Statistical Analyses
Statistical assessments/methods for safety, efficacy, PK/PD, and immunogenicity are found in 
Section 11 of the Core. In instances where the statistical analysis plan (SAP) might contradict the 
analyses specified in the Core, the SAP supersedes the Core.
Available data from Part A2 will be pooled with data from Part A by dose. In addition, efficacy 
data from Part A2 may be analyzed separately. The relationship between dose and safety/efficacy 
may be explored. Analyses by dose may be conducted for, but not limited to, the following 
endpoints: frequency of AEs of special interest, ORR, and percent reduction in tumor burden by 
dose. A generalized linear model may be used to adjust for covariates or to model the 
relationship. Because of the limited number of subjects, the above analyses will be conducted if 
data warrant.
10
DATA SAFETY MONITORING BOARD
The Data and Safety Monitoring Board (DSMB) will monitor the safety of the study. The DSMB 
will consist of individuals in relevant fields of expertise. It will convene on a regular basis (at 
least 2 times per year or at a different frequency as otherwise agreed) and will review all safety 
information to determine whether the study should continue unchanged or whether Module
modifications are required to ensure subject safety. Details on the DSMB are provided in 
Appendix D and in a separate DSMB charter. The DSMB will make recommendations to the 
Sponsor, who will make ultimate decisions regarding study alteration or discontinuation.


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11
INVESTIGATOR REQUIREMENTS AND QUALITY CONTROL 
11.1
Ethical Conduct of the Study
This study will be conducted in accordance with the current IRB/IEC approved clinical Module, 
Core, ICH Good Clinical Practice Guidelines, and relevant policies and requirements of the 
national regulations and laws, including the Health Insurance Portability and Accountability Act 
of 1996.
11.2
Institutional Review Board or Independent Ethics Committee
The IRB/IEC will meet all FDA requirements governing IRBs (21 Code of Federal Regulations 
[CFR] Part 56). 
The Investigator will provide the Sponsor (or designee) with documentation of IRB/IEC 
approval of the following documents before the study begins at the study site(s): Module, Core,
ICF, and any other relevant materials intended for or directed to subjects (eg, subject diaries, 
advertisements). The Investigator will supply documentation to the Sponsor of IRB/IEC 
requirements regarding continuing review and approval of revisions to any of these documents.
11.3
Subject Information and Informed Consent
Written informed consent/assent is required from each subject prior to any testing under this 
Module, including Screening tests and evaluations. The ICF, as specified by the clinical site’s 
IRB/IEC, must follow the Protection of Human Subjects regulations listed in 21 CFR Part 50.
The ICF will be used to explain the risks and benefits of study participation in simple terms 
before the subject will be entered into the study. The ICF will contain a statement that the 
consent is freely given, that the subject is aware of the risks and benefits of entering the study, 
and that the subject is free to withdraw from the study at any time. Written informed consent 
must be given by the subject after the receipt of detailed information on the study. It is the 
responsibility of the Investigator to obtain consent/assent and to provide the subject with a copy 
of the signed and dated ICF. Confirmation of a subject’s informed consent must also be 
documented in the subject’s medical record prior to any testing under this Module, including 
Screening tests and evaluations.
All ICFs used in this study must be approved by the appropriate IRB/IEC and by the Sponsor or 
its designee. The ICF must not be altered without the prior agreement of the relevant IRB/IEC 
and the Sponsor.


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11.4
Retention of Records
The Investigator must maintain essential study documents (Core, Module, Module amendments, 
completed eCRFs, signed ICFs, relevant correspondence, and all other supporting 
documentation) until at least 2 years after the last approval of a marketing application in an ICH 
region and until there are no pending or contemplated marketing applications in an ICH region or 
at least 2 years after the formal discontinuation of clinical development of the investigational 
product. These documents will be retained for a longer period if required by the applicable 
regulatory requirements or the hospital, institution, or private practice in which the study is being 
conducted. Subject ID codes (subject names and corresponding study numbers) will be retained 
by the site for this same period of time. These documents may be transferred to another 
responsible party, acceptable to the Sponsor, who agrees to abide by the retention policies. 
Written notification of transfer must be submitted to the Sponsor. The Investigator or designee 
must contact the Sponsor prior to disposing of any study records.
11.5
Publication Policy
All information concerning Probody therapeutics is considered confidential and shall remain the 
sole property of the Sponsor. The Investigator agrees to use this information only in conducting 
the study and shall not use it for any other purposes without written approval from the Sponsor. 
No publication or disclosure of study results will be permitted except as specified in a separate, 
written agreement between Sponsor and the Investigator.
11.6
Financial and Insurance
Financing and insurance are addressed in a separate document.


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12
STUDY ADMINISTRATIVE INFORMATION
12.1
Protocol Amendments
Changes to the conduct of the study will be prepared by the Sponsor as an amendment to the 
Module and/or the Common Core Document and implemented only upon joint approval of the 
Sponsor, or a representative of the Sponsor, and the Investigator(s). Amendments should also 
receive written IRB/IEC approval prior to implementation, except when necessary to eliminate 
immediate hazards to the subjects or when the changes involve only logistical or administrative 
aspects of the trial (eg, change of monitor, telephone numbers). In this case, the Sponsor will 
amend and implement the Module change and subsequently notify the regulatory authorities 
and/or the IRB, as appropriate.
12.2
Address List
12.2.1
Sponsor
CytomX Therapeutics, Inc.
151 Oyster Point Boulevard, Suite 400
South San Francisco, CA 94080-1913
Telephone: +1-650-515-3185
Fax: 
+1-650-351-0353
12.2.2
Contract Research Organization
Medpace, Inc.
5375 Medpace Way
Cincinnati, OH 45227
Telephone: +1-513-579-9911
Fax:
+1-513-579-0444
12.2.3
Drug Safety
Medpace Clinical Safety
5375 Medpace Way
Cincinnati, OH 45227
Telephone: +1-800-730-5779, dial 3 or +1-513-579-9911, dial 3
Fax:
+1-866-336-5320 or +1-513-579-0444
12.2.4
Biological Specimens
Medpace Reference Laboratories
5365 Medpace Way
Cincinnati, OH 45227
Telephone: +1-513-366-3270
Fax:
+1-513-366-3273


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CytomX Therapeutics, Inc.
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Appendix A:
Common Core Document CTMX-C-001


Common Core Document: CTMX-C-001 
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AN OPEN-LABEL, DOSE-FINDING AND PROOF OF 
CONCEPT STUDY FOR PROBODY™ THERAPEUTICS 
(PROBODY TX) IN SUBJECTS WITH METASTATIC OR 
LOCALLY ADVANCED UNRESECTABLE SOLID 
TUMORS AND/OR LYMPHOMAS 
COMMON CORE DOCUMENT: CTMX-C-001 
 
Product: 
Probody technology platform 
Sponsor: 
CytomX Therapeutics, Inc. 
151 Oyster Point Boulevard, Suite 400 
South San Francisco, CA 94080-1913 
Tel: (650) 515-3185 
Fax: (650) 351-0353 
Chief Medical Officer: Rachel W. Humphrey, MD 
Senior Vice President 
CytomX Therapeutics, Inc. 
Tel: (203) 435-2152 
Date of Common Core 
Document: 
24 June 2016 
 
Date of Common Core 
Document 01: 
 
11 November 2016 
Date of Common Core 
Document 02: 
 
11 May 2018 
CONFIDENTIALITY STATEMENT 
This document contains confidential information, which should not be copied, referred to, released, or published without written 
approval from CytomX Therapeutics, Inc. Information provided in this document may be subject to change and revision. Your 
acceptance of this document constitutes agreement that you will not disclose the information contained herein to others without 
written authorization from CytomX Therapeutics, Inc. 




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2. 
SYNOPSIS 
Name of Sponsor: 
CytomX Therapeutics, Inc. 
Title of study: 
An Open-Label, Dose-Finding and Proof of Concept Study for Probody™ (Probody Tx) Therapeutics 
in Subjects with Metastatic or Locally Advanced Unresectable Solid Tumors and/or Lymphomas 
Investigators / Study center(s): Multicenter program to be conducted globally 
Phase of development: 
Dose-finding and proof of concept 
Introduction and Study Rationale: 
Probody™ therapeutics (Probody Txs) are fully recombinant antibody prodrugs, activated 
preferentially by proteases associated with tumor microenvironments. They are designed to be 
administered in a form that can be switched on in the tumor microenvironment, with minimal 
interaction with its target in normal circulating cells or with healthy tissues. In this way, Probody Txs 
are expected to minimize injury outside of the tumor while maintaining anti-tumor activity. This 
antibody-masking technology can be potentially applied to any antibody-based treatment and be 
particularly useful in settings where clinical utility is limited by significant toxicities due to target 
binding outside of the tumor. 
To simplify evaluation of the Probody platform, the program includes a central Common Core 
Document (Core) and drug-specific protocol modules. The Common Core Document describes all 
design features related to a standard Phase 1-2 protocol (dose escalation and expansion) that would be 
applicable to all Probody Txs and combinations. All protocol elements related to subject selection and 
patient care are in the drug-specific protocol modules. 
Common Core Document Overall Objectives (relevant to all Probody Modules)  
Primary: 
x 
To evaluate the safety and tolerability of multiple doses of the Probody Tx, administered 
intravenously, as monotherapy and/or as part of selected combination regimens, to subjects 
with metastatic or locally advanced unresectable solid tumors and/or lymphomas 
x 
To determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of the 
Probody Tx (as monotherapy and/or in select combinations)  
Secondary: 
x 
To obtain preliminary evidence of anti-cancer activity for the Probody Tx (as monotherapy 
and/or in combination) in subjects with advanced or unresectable solid tumors (during 
dose-finding) as well as in specific select tumor types (during additional efficacy evaluation) 
o Objective Response Rate (ORR) by the Response Evaluation Criteria in Solid Tumors 
(RECIST) or tumor-specific criteria, as applicable (eg, The Lugano Classification for 
lymphoma) 
o ORR by the modified immune-related RECIST criteria will also be determined for 
Probody Txs likely to be immunostimulating 
o Time to tumor response (TTR) 
o Duration of response (DOR) 


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o Progression-free survival (PFS) 
o Overall survival (OS) 
x 
To characterize the PK of the Probody Tx administered as directed 
x 
To assess the incidence of anti-drug antibody (ADA) formation to the Probody Tx 
Exploratory: 
x 
To assess mechanistic features that are common to all Probody Txs (eg, release of the mask in 
tumor vs non-tumor tissue) 
x 
To assess additional PD markers as per individual Probody Tx-specific Protocol Modules 
Overview of Study Design and Schema: 
This is an open-label, multiple-dose, dose-finding program of Probody Txs (as monotherapy and/or in 
combination with other anti-cancer agents) in subjects with advanced solid tumors and/or lymphomas. 
Additional evaluation of safety and efficacy in select cancer types will be pursued for each Probody Tx 
monotherapy and/or combination regimens, respectively, as defined in each Probody Tx-specific 
Protocol Module. 
Dose-Finding: Escalation cohorts will be planned for a given Probody Tx, as monotherapy and/or in 
combination. This period of the program is designed to evaluate safety, pharmacokinetics (PK), 
pharmacodynamics (PD), and gauge preliminary anti-tumor activity in subjects with advanced solid 
tumors and/or lymphomas. 
The doses to be evaluated for each regimen (monotherapy and/or combination), as well as the number 
of cohorts, will be defined in the Probody Tx-specific Module. The general schema, however, is 
common to all Modules and presented here as follows. 
Initially, 1-3 subjects will be enrolled into each dosing cohort, as defined by the Probody Tx-specific 
Module. Cohort expansion and dose escalation will be based on the number of DLTs experienced (see 
below) and after consultation by the Sponsor with a panel of active program investigators who will 
serve as the Safety Review Committee (SRC) and advise the Sponsor for all modules of this 
core/module program as long as the program is open.  
To further explore the relationship between dose and emerging safety or efficacy signals, additional 
subjects  may be accrued at any dose level as specified in the module. 
Escalation of the Probody Tx in combination and/or monotherapy will be initiated and continue until 
the pre-specified top dose is administered safely, the MTD is defined or another interim dose is chosen 
as dictated by the data. 
Efficacy Expansions for Proof of Concept: Further characterization of safety and efficacy will be 
conducted at the chosen dose and regimen, in a restricted number of pre-selected cancer types, in 
additional subjects as specified in the module.  Additional subjects may be enrolled in an expansion 
cohort to further characterize efficacy. More than one dose level of each regimen may be tested, 
depending on the outcome of the dose escalation portion of the study. 
Generally, all subjects will be followed until death, either in the Probody-specific module or a rollover 
follow-up trial. A separate unified rollover module may be used for continued follow-up for all subjects 
experiencing clinical benefit on any Probody Tx who remain on study drug and/or are still in 
follow-up.  
Eligibility Criteria / Treatment: 
Eligibility criteria and investigational product (IP) and reference therapy dosage and mode of 
administration will be specified in the Probody Tx-specific Module. 


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Duration of Treatment: 
The maximum duration of study treatment for an individual subject enrolled in the study will be 
defined in each module. In general, subjects will continue on treatment unless they: 
x 
experience clinically significant disease progression 
x 
are unwilling or unable to adhere to the protocol 
x 
withdraws consent or is lost to follow-up 
x 
experience an intercurrent illness that prevents further administration of IP and/or reference 
therapy 
x 
experience a DLT or an adverse event (AE) related to study drug(s), which precludes further 
administration of the study drug(s)  
x 
experience a prolonged treatment delay (as per the Probody Tx-specific module) 
x 
become pregnant, either prior to the first dose of study drug or at any time during treatment 
Additionally  
x 
The investigator may determine that the subject should discontinue treatment  
x 
The Sponsor may terminate the study. 
Criteria for evaluation 
Efficacy: 
For all Probody Txs, the primary criteria for defining efficacy and also for management of patient care 
will be RECIST (version 1.1) or tumor-specific response criteria (eg, Lugano Classification for 
lymphomas). However, response by the modified irRECIST criteria may also be captured for analysis 
in subjects receiving Probody Txs that are likely to be immunostimulating. 
Safety: 
Incidence and nature of DLTs, AEs and serious AEs (SAEs), as well as physical examinations, vital 
sign measurements, triplicate electrocardiograms (ECGs), clinical laboratory evaluations, and treatment 
discontinuation due to toxicity will be evaluated for safety assessment. 
Pharmacokinetics:  
The following PK parameters will be generated for the Probody Tx (as monotherapy and/or as a part of 
a combination regimen): maximum concentration (Cmax), time at maximum concentration (tmax), 
minimum concentration (Cmin), volume of distribution (Vd), elimination half-life (T½), elimination rate 
FRQVWDQWȜ]DUHDXQGHUWKHFXUYH$8&0-t and AUC0-inf) following single-dose, AUC0-Ĳ for multiple 
dose, total apparent clearance (CL), and fluctuation (%PTF). Metabolic activation of the Probody may 
also be explored. 
Pharmacodynamics:  
Assays of tumor tissue, blood cells, and plasma or serum meant specifically to measure Probody Tx 
target binding or effect on cellular activity, may be conducted. 
Immunogenicity: 
Blood samples will be collected to assess the extent of ADA response to Probody Txs. Incidence and 
titer of anti-Probody Tx antibodies will be defined. 


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Statistical Analyses: 
ORR is the primary efficacy endpoint. For solid tumors, response evaluation will be based on RECIST 
criteria (v1.1). In addition, immune-related RECIST (irRECIST) criteria will also be used for Probody 
Txs that are likely to be immunostimulating. Objective response in lymphoma will be based on 
tumor-specific criteria. 
Descriptive summaries will be provided. For continuous measures, these include mean, median, 
standard deviation and range. For categorical measures, these include counts and percentages. 
Time to tumor response and duration of response will be summarized for those subjects with confirmed 
responses. PFS and OS will be summarized by Kaplan-Meier methodology.  
The safety parameters include: AEs, clinical laboratory tests, physical examinations, vital signs, ECOG 
performance status, ECGs, and immunogenicity tests. Safety parameters may be summarized using 
descriptive statistics. 
Plasma concentrations and PK parameters will be summarized using descriptive statistics. The 
relationship between biomarker and efficacy endpoints may be explored.  
Administrative interim analyses on safety and efficacy or on PK, immunogenicity, and selected 
biomarkers may be performed at several times prior to completion of the study in order to facilitate 
program decisions and to support study presentations or publications.  
 


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3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES  


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TABLE OF CONTENTS 
1. 
SIGNATURE PAGE ....................................................................................................2 
1.1. 
Sponsor Approval .........................................................................................................2 
1.2. 
Investigator Agreement ................................................................................................2 
2. 
SYNOPSIS ...................................................................................................................3 
3. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES .................7 
4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .............................14 
5. 
INTRODUCTION ......................................................................................................18 
5.1. 
Probody™ Therapeutics .............................................................................................18 
5.2. 
Study Rationale ...........................................................................................................19 
6. 
STUDY OBJECTIVES ..............................................................................................21 
6.1. 
Primary Objectives .....................................................................................................21 
6.2. 
Secondary Objectives .................................................................................................21 
6.3. 
Exploratory Objectives ...............................................................................................21 
7. 
INVESTIGATIONAL PLAN .....................................................................................22 
7.1. 
Study Characteristics ..................................................................................................22 
7.2. 
Program Design ..........................................................................................................22 
7.3. 
Enrollment ..................................................................................................................23 
7.4. 
Blinding and Randomization ......................................................................................23 
7.5. 
Pregnancy ...................................................................................................................23 
8. 
INVESTIGATIONAL PRODUCT ............................................................................25 
8.1. 
IP Accountability ........................................................................................................25 
8.1.1. 
Drug Inventory ............................................................................................................25 
8.1.2. 
Return of IP .................................................................................................................25 
8.2. 
Subject Compliance ....................................................................................................26 
9. 
TREATMENT OF SUBJECTS ..................................................................................27 
9.1. 
Dosage and Administration ........................................................................................27 
9.1.1. 
Study Drug Preparation and Administration ..............................................................27 
9.1.2. 
Cohort Initiation ..........................................................................................................27 
9.1.3. 
Dose-Finding ..............................................................................................................27 
9.2. 
Dose Escalation Guidelines ........................................................................................27 
9.3. 
Dose-Limiting Toxicity (DLT) and Maximally Tolerated Dose (MTD) ...................28 


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9.4. 
Dose Modifications and Dosing Delays Due to Toxicity ...........................................28 
9.5. 
Additional Safety Cohorts (Expansion) ......................................................................28 
9.6. 
Safety Monitoring .......................................................................................................29 
9.7. 
Prior and Concomitant Medications ...........................................................................29 
9.8. 
Continuation of Study Treatment ...............................................................................30 
9.9. 
Withdrawal of Subjects ...............................................................................................30 
9.9.1. 
Withdrawal Criteria ....................................................................................................30 
9.9.2. 
Withdrawal from Treatment .......................................................................................31 
9.9.3. 
Withdrawal from Study ..............................................................................................31 
9.9.4. 
Replacement of Subjects .............................................................................................31 
10. 
SAFETY, EFFICACY, PK, PD, AND OTHER ASSESSMENTS ............................32 
10.1. 
Safety ..........................................................................................................................32 
10.1.1. 
Adverse Events ...........................................................................................................32 
10.1.2. 
Clinical Laboratory Tests ...........................................................................................32 
10.1.2.1. 
Hematology .................................................................................................................32 
10.1.2.2. 
Serum Chemistry ........................................................................................................32 
10.1.2.3. 
Thyroid Function ........................................................................................................33 
10.1.2.4. 
Immune Safety Assays ...............................................................................................33 
10.1.2.5. 
Coagulation .................................................................................................................33 
10.1.2.6. 
Urinalysis ....................................................................................................................33 
10.1.2.7. 
Pregnancy ...................................................................................................................33 
10.1.3. 
Other Safety Measures ................................................................................................33 
10.1.3.1. 
Vital Signs ..................................................................................................................33 
10.1.3.2. 
Electrocardiogram (ECG) ...........................................................................................33 
10.1.3.3. 
Physical Exam ............................................................................................................34 
10.1.3.4. 
Ophthalmology Exam .................................................................................................34 
10.1.3.5. 
Concomitant Medications/Therapies ..........................................................................34 
10.1.3.6. 
Eastern Cooperative Oncology Group (ECOG) Performance Status .........................34 
10.2. 
Efficacy .......................................................................................................................34 
10.2.1. 
Imaging .......................................................................................................................35 
10.2.2. 
Tumor Markers ...........................................................................................................35 
10.2.3. 
Response Criteria ........................................................................................................35 


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10.2.3.1. 
RECIST v1.1 ...............................................................................................................36 
10.2.4. 
Definitions of Treatment Outcomes: RECIST v1.1 ...................................................37 
10.2.4.1. 
Modified immune-related RECIST (irRECIST) ........................................................38 
10.2.4.2. 
Tumor-Specific Response Criteria .............................................................................39 
10.3. 
Pharmacokinetics ........................................................................................................42 
10.4. 
Immunogenicity ..........................................................................................................42 
10.5. 
Pharmacodynamics .....................................................................................................42 
10.6. 
Exploratory Immune Function Evaluations ................................................................42 
11. 
STATISTICAL PLAN AND ANALYSIS .................................................................43 
11.1. 
Demographic and Baseline Characteristics ................................................................43 
11.2. 
Safety Analysis ...........................................................................................................43 
11.3. 
Efficacy Analysis ........................................................................................................43 
11.3.1. 
Efficacy Analysis Methods .........................................................................................44 
11.4. 
Pharmacokinetic Analysis ..........................................................................................44 
11.5. 
Immunogenicity ..........................................................................................................44 
11.6. 
Exploratory Analysis ..................................................................................................45 
11.7. 
Determination of Sample Size ....................................................................................45 
11.8. 
Interim Analysis ..........................................................................................................45 
11.9. 
Deviation from Original Analysis Plan ......................................................................45 
12. 
ADVERSE EVENTS ..................................................................................................46 
13. 
ETHICS ......................................................................................................................47 
14. 
STUDY ADMINISTRATION ...................................................................................48 
14.1. 
Administrative Structure .............................................................................................48 
14.2. 
Quality Control and Quality Assurance ......................................................................48 
14.2.1. 
Overview .....................................................................................................................48 
14.2.2. 
Monitoring ..................................................................................................................48 
14.2.3. 
Data Management/Coding ..........................................................................................49 
14.2.4. 
Quality Assurance Audit .............................................................................................49 
14.3. 
Data Handling and Recordkeeping .............................................................................49 
14.3.1. 
Electronic Data ...........................................................................................................49 
14.3.2. 
Case Report Form Completion ...................................................................................50 
14.3.3. 
Data Handling .............................................................................................................50 


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14.3.4. 
Retention of Study Records ........................................................................................50 
14.4. 
Financing and Insurance .............................................................................................50 
14.5. 
Confidentiality ............................................................................................................50 
14.6. 
Publication Policy .......................................................................................................51 
14.7. 
Direct Access to Source Data .....................................................................................51 
14.8. 
Protocol Amendments ................................................................................................51 
15. 
REFERENCES ...........................................................................................................52 
16. 
APPENDICES ............................................................................................................53 
16.1. 
ECOG Performance Status .........................................................................................53 
16.2. 
Modified Immune Related Response Evaluation Criteria in Solid Tumors 
Guidelines for Tumor Response .................................................................................54 
16.3. 
Lugano Classification for Lymphomas ......................................................................57 
16.3.1. 
Recommendations for Revisions to Staging Criteria ..................................................57 
16.3.2. 
Assessment of Response .............................................................................................57 


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LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................14 
Table 2: 
Common Core Document vs Module Components ....................................................22 
Table 3: 
Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines for 
Tumor Response .........................................................................................................37 
Table 4: 
Overall Response Criteria (RECIST v1.1) .................................................................38 
Table 5: 
Derivation of modified irRECIST Overall Responses ...............................................39 
Table 6: 
Response Criteria for Lymphoma ...............................................................................40 
 


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LIST OF FIGURES 
Figure 1: 
Relationship of Common Core Document and Protocol Modules .............................20 
 


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4. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Table 1: 
Abbreviations and Specialist Terms 
Abbreviation or 
Specialist Term 
Explanation 
%PTF 
fluctuation 
ACLS 
Advanced Cardiac Life Support 
ACTH 
adrenocorticotropic hormone 
ADA 
anti-drug antibody 
ADC 
antibody-drug conjugate 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANA 
antinuclear antibody 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
AUC0-inf 
area under the concentration time-curves from time zero to infinity 
BMB 
bone marrow biopsy 
BUN 
blood urea nitrogen 
CBC 
complete blood count 
CL 
total apparent clearance 
Cmax 
maximum observed plasma concentration 
Cmin 
minimum observed plasma concentration 
CMR 
complete metabolic response 
CR 
complete response 
CRF 
case report form 
CRO 
Contract Research Organization 
CRP 
C-reactive protein 
CSR 
clinical study report 
CT 
computerized (or computed) tomography 
CTLA-4 
cytotoxic T-lymphocyte-associated antigen 4 
CV 
cardiovascular 
CXR 
chest x-ray 
DLBCL 
diffuse large B-cell lymphoma 


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Abbreviation or 
Specialist Term 
Explanation 
DLT 
dose-limiting toxicities 
DOR 
duration of response 
ECG 
electrocardiogram/electrocardiography 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EOS 
End of Study 
EOT 
End of Treatment 
FDG 
fluorodeoxyglucose 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
HCG 
human chorionic gonadotropin 
HIPAA 
Health Insurance Portability and Accountability Act 
HL 
Hodgkin Lymphoma 
ICF 
informed consent form 
ICH 
International Conference on Harmonization 
ID 
identification 
IEC 
Independent Ethics Committee 
INR 
international normalized ratio 
IP 
investigational product 
IRB 
Institutional Review Board 
irPD 
immune-related Progressive Disease 
IRR 
infusion-related reaction 
irRC 
immune-related Response Criteria 
irRECIST 
immune-related Response Evaluation Criteria In Solid Tumors 
IV 
intravenous 
LD 
longest diameter 
LDH 
lactate dehydrogenase 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
MedDRA 
medical dictionary for regulatory activities 


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Abbreviation or 
Specialist Term 
Explanation 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
ORR 
objective response rate 
OS 
overall survival 
PD 
progressive disease 
PD-1 
programmed cell death 1  
PD-L1 
programmed cell death ligand 1  
PET 
positron emission tomography 
PFS 
progression-free survival 
PK/PD 
pharmacokinetic/pharmacodynamic 
PR 
partial response 
Probody Tx 
Probody therapeutic 
Probody™ 
Probody is a trademark of CytomX Therapeutics, Inc. 
PT 
prothrombin time 
PTT 
partial thromboplastin time 
QA 
quality assurance 
QC 
quality control 
RBC 
red blood cell 
RECIST 
Response Evaluation Criteria In Solid Tumors 
RF 
rheumatoid factor 
SAE 
serious AE 
SAP 
statistical analysis plan 
SAR 
suspected adverse reaction 
SD 
stable disease 
SGOT 
serum glutamic-oxaloacetic transaminase 
SGPT 
serum glutamic pyruvic transaminase 
SGPT 
serum glutamic-pyruvic transaminase 
SOP 
standard operating procedure 
SPD 
sum of the perpendicular diameters 
SRC 
Safety Review Committee 


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Abbreviation or 
Specialist Term 
Explanation 
SUSAR 
serious and unexpected suspected adverse reaction 
T½  
terminal elimination half-life 
TCB 
T-cell redirecting bispecifics 
Tmax 
time to maximum observed plasma concentration 
TMF 
trial master file 
TMTB 
total measured tumor burden 
TSH 
thyroid-stimulating hormone 
TTR 
time to tumor response 
Vd 
volume of distribution 
Vss 
steady state volume of distribution 
WBC 
white blood cell 
WHO DDE 
World Health Organization Drug Dictionary Enhanced 
WOCBP 
women of childbearing potential 


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5. 
INTRODUCTION 
5.1. 
Probody™ Therapeutics 
The use of antibody-based therapies for the treatment of cancer has greatly improved the 
precision by which tumor proteins and oncogenic pathways are targeted. Nevertheless, tumor 
targets are rarely, if ever, completely tumor-specific, and despite antibody precision, significant 
toxicities can result from antibody binding to normal tissue. A small number of tumor targets are 
expressed highly in the tumor and at low levels in normal tissue, but these have limited clinical 
utility because they are expressed only in a small number of tumor types and/or are present in a 
small number of subjects within a given tumor type. There is a need to identify new methods for 
optimizing the delivery of anti-cancer antibody-based therapeutics to widen the therapeutic index 
in the majority of patients. 
Many examples of the need for antibody-based therapies with improved safety can be cited. For 
example, antibody-based immunotherapies are particularly impacted by serious on-target 
toxicities. Despite the importance of cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), 
programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) as inhibitors of 
anti-tumor immunity, these proteins also serve as important protection against unwanted 
inflammation outside of the cancer. Severe, often life-threatening, inflammation can be observed 
in subjects receiving CTLA-4 inhibitors (eg, ipilimumab and tremelimumab), PD-1 inhibitors 
(eg, nivolumab and pembrolizumab) as well as PD-L1 inhibitors (eg, durvalumab and 
alemtuzumab). The on-target toxicities of these agents are particularly problematic when they are 
combined with each other, because synergy of efficacy in the tumor is associated with synergy of 
toxicity in normal tissues.  
Another example is the T-cell redirecting bispecific antibodies (TCBs). The extreme potency of 
TCBs is responsible for both the promise of these therapies and the difficulty in using them 
safely, particularly in solid tumors. An EGFR/CD3 bispecific (Micromet), for example, was 
highly and potently effective in mouse tumor models, but demonstrated diffuse organ 
inflammation in cynomolgus monkeys, and those animals that achieved the projected therapeutic 
exposure needed to be terminated early (Lutterbuese et al, 2010). Development of the agent was 
discontinued. Finally, antibody-drug conjugate (ADC) therapy can also be negatively affected by 
on-target toxicities. For example, a promising ADC directed against EphA2 (based on 
nonclinical data) was poorly tolerated in the first Phase 1 cohort in subjects and clinical 
development was discontinued (Annunziata et al, 2013). 
Thus the need for safer, more effective anti-cancer drugs remains a key medical need and 
enhancing tumor specific targeting may be critical in order to safely deliver to subjects very 
potent therapies.  
Probody therapeutics are fully recombinant antibody prodrugs, activated preferentially by 
proteases present in tumor microenvironments. They are designed to be administered in a form 
that has reduced interaction with their target in healthy tissues, but are activated to fully engage 
their target in the tumor microenvironment. In this way, Probody therapeutics are expected to 
minimize toxicity while maintaining anti-tumor activity. This approach may be particularly 


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useful for antibody-based therapies where clinical utility is limited by significant toxicities due to 
target binding outside of the tumor. Probody therapeutics differ from unmodified monoclonal 
antibodies by the recombinant inclusion of a prodomain at the amino-terminus of the light chain, 
which blocks (or “masks”) the antibody binding to its target antigen and can be removed by 
tumor-associated protease activity. The physicochemical and pharmacological behaviors of 
Probody therapeutics are similar to unmodified monoclonal antibodies in most respects, although 
normal tissue binding and, therefore, target-mediated clearance are diminished. This 
antibody-masking technology can be potentially applied to monoclonal antibodies, antibody drug 
conjugates, bispecific antibodies, and broadly to any antibody-based, anti-cancer therapy. 
In summary, by using refined applications of tumor protease biology, antibody-prodrugs can be 
engineered to be preferentially activated in tumors and spare normal tissue. The technology 
offers the potential to improve the therapeutic window of antibody-based agents with validated 
targets and create a therapeutic window with potent agents that can’t otherwise be safely 
administered. 
5.2. 
Study Rationale 
Features of the Probody technology warrant a single expanding protocol for evaluation of 
multiple Probodies.  
First, mechanisms of Probody activation are likely common to all Probody therapeutics 
(Probody Txs) and this is best assessed and analyzed in the same study. For example, assays that 
define the rate and location of Probody activation will be employed for all Probody Txs in 
development. Also, while the preclinical data show a characteristic level of activated Probody in 
the circulation of healthy animals, the extent of activation in subjects with concomitant 
morbidities will not be known until the clinical studies are initiated. A refined understanding of 
the subject population that is best served by the administration of antibody-based prodrugs that 
rely on active proteases for full function likely warrants the evaluation of a large sample size 
under the supervision of an experienced set of clinicians. 
Finally, while the preclinical data show a characteristic level of activated Probody in the 
circulation of healthy animals, the extent of activation in subjects with concomitant morbidities 
will not be known until the clinical studies are initiated. A refined understanding of the subject 
population that is best served by the administration of antibody-based prodrugs that rely on 
active proteases for full function likely warrants the evaluation of a large sample size under the 
supervision of an experienced set of clinicians.  
As such, the current program is constructed to permit unified clinical oversight of the entire 
Probody Tx program and is designed (for the sake of simplicity) as two broad parts: a Common 
Core Document that represents a standard Phase 1-2 design with all of the common elements that 
are relevant to any Probody in early development. This large and stable document will serve as 
the centerpiece of the study. Concise, Probody Tx-specific Modules will guide the investigator to 
study features unique to the investigational Probody Tx under evaluation. All protocol elements 
that directly guide patient care are in the module. 
To maintain clarity and simplicity in the review and conduct of the program, institutional review 
board/independent ethics committee (IRB/IEC) submissions for each new Probody Tx will 
include the Common Core Document and relevant protocol module as a single package.  


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Amendments to the Common Core Document or to the modules, respectively, will be handled 
independently and a clinical study report (CSR) will be written for each module. The 
core/module system is a mechanism for bundling the clinical evaluation of Probody Txs under 
one program with a common study design, sites, investigators, database, and oversight. The 
figure below represents the relationship of the Probody Tx-specific protocol modules to the 
Common Core Document. 
Figure 1: 
Relationship of Common Core Document and Protocol Modules  
 


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6. 
STUDY OBJECTIVES 
The objectives below apply to the Phase 1-2 studies conducted under the Core.  
6.1. 
Primary Objectives 
x To evaluate the safety and tolerability of multiple doses of the Probody Tx, 
administered intravenously, as monotherapy and/or as part of a select combination 
regimen, to subjects with metastatic or locally advanced unresectable solid tumors 
and/or lymphomas; and 
x To determine the MTD and DLTs of the Probody Tx (as monotherapy and/or in select 
combinations).  
6.2. 
Secondary Objectives 
x To obtain preliminary evidence of anti-cancer activity for the Probody Tx (as 
monotherapy and/or in combination) in subjects with advanced or unresectable solid 
tumors (during dose-finding) as well as in specific select tumor types (during 
additional efficacy evaluation) 
 ORR by RECIST or tumor-specific criteria, as applicable (eg, The Lugano 
Classification for lymphoma) 
 ORR by the modified immune-related RECIST criteria will also be determined 
for Probody Txs likely to be immunostimulating  
 Time to tumor response (TTR) 
 Duration of response (DOR) 
 Progression-free survival (PFS) 
 Overall survival (OS) 
x To characterize the PK of the Probody Tx administered as directed 
x To assess the incidence of anti-drug antibody (ADA) formation to the Probody Tx 
6.3. 
Exploratory Objectives 
Exploratory objectives that may be included: 
x To assess mechanistic features that are common to all Probodies (eg, release of the 
mask in tumor vs non-tumor tissue); and 
x To assess additional PD markers as defined in Probody Tx-specific protocol modules. 


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7. 
INVESTIGATIONAL PLAN 
7.1. 
Study Characteristics 
In order to simplify evaluation of the Probody platform, the current study is written in two parts, 
the Common Core Document, which focuses on definitions and analysis plan, and the Probody 
Tx-specific Protocol Module, which contains all elements related to patient care. Table 2 outlines 
the components contained with the Common Core vs the Protocol Module. 
Table 2: 
Common Core Document vs Module Components 
Element 
Common Core Document 
Protocol Module 
Synopsis 
X 
 
Introduction 
Platform-specific 
Probody-specific 
Objectives 
X 
X 
Number of Subjects 
General 
Module-specific 
Investigational Plan 
X 
 
Selection of Subjects 
 
X 
Investigational Product 
Drug Accountability 
Module-specific drug prep, storage, 
dosage form, administration 
Treatment of Subjects 
General dose escalation  
Specific dose escalation, AE 
management, dose modification, 
withdrawal criteria and other 
Probody Tx-specific features  
DLTs 
General Definitions 
DLT definition and drug-specific 
management guidelines  
Efficacy, Safety, PK, PD, ADA 
Efficacy assessment, safety 
parameters, etc. 
PK, PD, and ADA assessments 
Study Procedures 
List/description 
Schedule of Events 
Statistics 
X 
 
Adverse Events 
 
X 
Ethics 
 
X 
Study Administration 
Administrative procedures 
 
7.2. 
Program Design 
This is an open-label, dose-finding program of Probody Txs (as monotherapy and/or in 
combination with other anti-cancer agents) in subjects with advanced solid tumors and/or 
lymphomas. Additional evaluation of safety and efficacy in select cancer types will be pursued 
during the expansion phase of each module. The Probody Tx-specific module will specify the 
doses and cancers to be studied in expansion for the monotherapy and/or combination regimens, 
as applicable. 


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For the purposes of the Probody Tx program, “investigational product” refers to the Probody Tx. 
“Reference therapy” refers to any chemotherapeutic, biologic, or other anti-cancer therapy 
administered as part of the study. “Study drug” is used when referring to both IP and reference 
therapy. 
7.3. 
Enrollment 
The number of subjects enrolled will depend on the number of dose cohorts and treatment arms 
during dose escalation, as well as the cancers targeted in the expansion phase. This will be 
defined in the module. 
During the efficacy expansion period of the study, a cohort is defined by the regimen 
(monotherapy and/or specific combination) and individual cancer type. Based on statistical 
calculations, additional  subjects may be enrolled to each cohort as specified in the module. 
Additional subjects may be enrolled in an expansion cohort to further characterize efficacy. 
Investigators will have the option of selecting among the treatment regimens outlined in the 
module for a particular subject; however, the doses to be administered will be assigned as 
determined by the dose escalation schema for the module. 
7.4. 
Blinding and Randomization 
Unless otherwise stated in the Probody Tx-specific module, all modules will be open-label and 
non-randomized.  
7.5. 
Pregnancy 
Pregnant women are not eligible for inclusion in the study. Measures to be taken to avoid 
pregnancy and to monitor subjects for potential pregnancy are outlined below. 
Prior to Start of Treatment 
Before enrolling women of childbearing potential (WOCBP) into a Probody Tx clinical trial, 
Investigators must advise WOCBP of the importance of avoiding pregnancy during trial 
participation and the potential risk factors of an unintentional pregnancy. 
WOCBP must agree to use an adequate method of contraception to avoid pregnancy throughout 
their participation in the study and for a period of at least 90 days after the last infusion of study 
drug, whichever is longer in duration. If male, the subject must agree to use an accepted method 
of contraception during the same period of time. In addition, because harmful effects may occur 
to a child who is breast feeding from a woman receiving a Probody Tx, female subjects must not 
breastfeed during their participation in the study and for 6 months after the last infusion of study 
drug, whichever is longer in duration. This should be covered during the informed consent 
process. 
All WOCBP must have a negative pregnancy test within 7 days prior to receiving the first 
infusion of study drug. If the pregnancy test is positive, the subject must not receive study drug 
and must not be enrolled in the study. 


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During the Study 
After the first Probody Tx infusion, pregnancy tests will be performed routinely while on 
treatment (at a frequency defined in the module), and at the End of Treatment visit. WOCBP 
must continue to have negative pregnancy tests throughout the study. The results of all 
pregnancy tests (positive or negative) must be recorded on the eCRF. 
In addition, all WOCBP or fertile men with partners of childbearing potential should be 
instructed to contact the Investigator immediately if they suspect they or their partner might be 
pregnant (eg, missed or late menstrual period) at any time during study participation. 
If, following initiation of study treatment, it is subsequently discovered that a subject is pregnant 
or may have been pregnant at the time of IP and/or reference therapy exposure, the IP and/or 
reference therapy will be discontinued. Exceptions to IP/reference therapy discontinuation may 
be considered for life-threatening conditions only after consultation with the Sponsor and 
Medical Monitor. The Investigator must immediately notify the Sponsor and Medical Monitor of 
this event and record the pregnancy on the eCRF.  
Protocol-required procedures for study discontinuation and follow-up must be performed on the 
subject unless contraindicated by pregnancy. Other appropriate pregnancy follow-up procedures 
should be considered if indicated.  


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8. 
INVESTIGATIONAL PRODUCT 
8.1. 
IP Accountability 
8.1.1. 
Drug Inventory 
The Investigator will be responsible for ensuring that the IP is used only in accordance with the 
approved Protocol Module, for maintaining IP accountability at the clinical trial site, and 
ensuring that a current record of IP disposition is maintained at the study site. Records or logs 
must comply with applicable regulations and guidelines, and should include: 
x The number of vials received and placed in the storage area, and date of receipt; 
x The number of vials currently in the storage area; 
x The lot number or batch number of each vial; 
x The dates and initials of the person responsible for inventory entry/movement of each 
vial; 
x The number of vials dispensed to each subject, with each subject identified by unique 
subject identifiers, and each vial used identified by lot/batch number; 
x The number of vials transferred to another area for dispensing or storage, and date of 
transfer; any transfer of study drug to another location (eg, satellite site) will require 
documentation of chain of custody and cold chain maintenance in accordance with 
product stability standards; 
x Non-study disposition (eg, vials that are lost or wasted); 
x The number of vials returned to the Sponsor or Sponsor’s designee, if applicable, and 
date of return; 
x The number of vials destroyed at the study site, if applicable, and date of destruction; 
and 
x Retained samples sent to a third party for bioavailability/bioequivalence, if 
applicable, and the date samples were sent.  
The Sponsor or the Sponsor’s designee will provide forms to facilitate inventory control if the 
staff at the investigational site does not have an established system that meets these 
requirements. 
8.1.2. 
Return of IP 
Upon completion or termination of the study, all unopened vials of IP must be returned to the 
Sponsor or Sponsor’s designee, according to Sponsor’s shipping instructions, unless authorized 
by the Sponsor or Sponsor’s designee to be destroyed at the site.  
x All vials of IP returned to the Sponsor or Sponsor’s designee must be accompanied by 
the appropriate documentation and clearly identified by the Probody Tx-specific 


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Module number and study site number on the outermost shipping container. Returned 
supplies should be in the original containers.  
x Empty or partially used containers should not be returned to the Sponsor or Sponsor’s 
designee. It is the Investigator’s responsibility to arrange for disposal of all partially 
used or empty containers, provided that procedures for proper disposal have been 
established according to applicable federal, state, local, and institutional guidelines 
and procedures, and provided that appropriate records of disposal are kept, including 
written authorization for disposal/destruction granted by the Sponsor or Sponsor’s 
designee, arrangement for disposal, and appropriate documentation and records of the 
disposal will be maintained. 
The return of unopened vials of IP should be arranged by the responsible study monitor. 
8.2. 
Subject Compliance 
IP and/or reference therapy administered as an intravenous (IV) infusion at the clinical site by 
the study staff will be documented in the subject’s medical record. In the case of oral 
medications, subject compliance may be monitored by the use of subject diaries, pill counts, or 
other methods to be specified on the study portal. Subjects will be encouraged to comply with all 
study procedures. 


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9. 
TREATMENT OF SUBJECTS 
9.1. 
Dosage and Administration 
9.1.1. 
Study Drug Preparation and Administration 
Refer to the Probody Tx-specific module for details pertaining to the dosing schedule(s), the 
route/mode(s) of administration, and the treatment period(s), including the follow-up period(s) 
for subjects for each trial treatment group of the specific study. 
9.1.2. 
Cohort Initiation 
Detailed information for Probody Tx-specific cohort initiation will be detailed in the modules; 
however, the first subject in each new dose cohort will be dosed a minimum of 1 day prior to any 
other subjects in that cohort, to allow for observation of possible severe and/or serious acute 
(eg, infusion-related) toxicities that might affect subsequent subject enrollment or dosing 
decisions. 
9.1.3. 
Dose-Finding 
Initially, 1-3 subjects will be enrolled into each cohort, as defined in the Probody Tx-specific 
module. Cohort expansion and dose escalation will be based on the number of DLTs 
experienced, as monotherapy and/or in combination with reference therapy. After establishing 
the DLT rate, additional subjects (monotherapy and/or combination therapy, respectively) may 
be enrolled to further evaluate the relationship between dose and safety or efficacy as specified 
in the module. 
Unless otherwise specified in the Probody Tx-specific module, the DLT evaluation interval is 
defined as up to 28 days after administration of the first dose of IP. 
9.2. 
Dose Escalation Guidelines 
Until a DLT RUWUHDWPHQWUHODWHG*UDGHrelated toxicity is observed requiring cohort 
expansion, single-subject cohorts may be explored at the beginning dose levels. In this way, the 
number of subjects exposed to subtherapeutic doses will be minimized.  
In this setting, as soon as a DLT is observed in a single-subject cohort, or a subject experiences a 
Grade 2 study drug-related adverse event (AE), or cohort escalation reaches a starting dose 
level as defined in the module, cohorts will be enrolled using the standard 3 + 3 design. Cohort 
escalation may only take place after all individuals in a given cohort have reached the end of the 
DLT window and the Sponsor has approved further dose escalation. 
Subjects who withdraw from the study for any reason during the DLT evaluation interval for 
reasons other than a DLT will be replaced. Dose escalation will proceed between cohorts 
according to the schema outlined in the module (or with smaller increments if significant AEs 
are observed). 


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After the rate of DLTs has been defined for a specific dose in 3 or 6 subject cohorts, additional 
subjects may be accrued at any dose level to better define the relationship between dose and 
emerging safety of efficacy signals, as specified in the module. 
Escalation of the Probody Tx as monotherapy will be initiated first, and continue until the 
pre-specified top dose is administered safely or the maximum tolerated dose (MTD) is defined, 
whichever comes first. 
Separate tracks of dose escalation of each combination regimen within a module, may also be 
conducted. The timing of initiation of the combination evaluation will differ, depending on the 
Probody Tx under evaluation (and as characterized in the relevant module). Initiation of 
combination evaluation could be as early as the time of successful clearing of monotherapy 
Cohort 2 and after consultation with the SRC. The dose of the combination agent(s) will be 
defined in each Probody Tx-specific module.  
Once combination dose escalation has been initiated, it will proceed independently of the 
monotherapy escalation and continue until the pre-specified top doses for each agent are 
administered safely or the MTD is defined, whichever comes first. However, at the time of any 
dose escalation decision, the Sponsor and SRC will review available safety data from the 
monotherapy and/or combination cohort before a decision to escalate is made. 
If one of the planned dose cohorts is determined to exceed the MTD and/or a review of ongoing 
safety/tolerability supports testing an intermediate dose, an alternative dose escalation schema 
may be explored. Escalation steps will not exceed those stipulated in the module without a 
formal amendment. 
Subjects may be permitted individual dose escalations if indicated in a specific module. 
9.3. 
Dose-Limiting Toxicity (DLT) and Maximally Tolerated Dose (MTD) 
All AEs will be captured according to the National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI CTCAE) v4.03 and considered DLTs. Refer to the Probody 
Tx-specific module for detailed information. 
Grade 1 or 2 AEs will not be considered DLTs unless specified in Probody Tx-specific Modules. 
9.4. 
Dose Modifications and Dosing Delays Due to Toxicity 
Drug-specific dose modifications and management of AEs are discussed in the module. 
9.5. 
Additional Safety Cohorts (Expansion)  
To further characterize safety and efficacy of each regimen at the chosen dose in a restricted 
number of pre-selected cancer types, additional subjects in each cancer type may be enrolled. 
Additional subjects may be enrolled in an expansion cohort to further characterize efficacy. More 
than one dose level of each regimen may be tested, depending on the outcome of dose escalation. 
All subjects will be followed until death, as long as the Module is still open.  
Archived samples or fresh baseline biopsies may be mandatory for subjects enrolled to the study. 
Requirements for on-treatment biopsies will be outlined in the Probody Tx-specific module. 


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9.6. 
Safety Monitoring 
Study drug administration should always be conducted in a facility equipped to manage severe 
adverse events such as anaphylaxis or cardiac arrest (eg, monitor/defibrillator, epinephrine and 
other Advanced Cardiac Life Support [ACLS] medications, intubation equipment, etc). 
Each subject receiving a Probody Tx will be evaluable for safety. The safety parameters include 
laboratory values, vital signs, physical findings, and spontaneous reports of adverse events 
reported to the Investigator by subjects. 
Each subject will be assessed periodically for the development of any toxicity and assessed 
according to the NCI CTCAE v4.03. 
Refer to the Probody Tx Investigator Brochure for a summary of the possible risks and side 
effects. Refer to the module for the management of acute (allergic reactions) and non-acute 
toxicity. Further management will depend upon the judgment of the Investigator in consultation 
with the Medical Monitor, as necessary. 
A Safety Review Committee (SRC) comprised of at least 3 members, including participating 
Investigators and CytomX Medical Monitor(s) will monitor AE data. This committee will review 
available dosing and safety study data from the current and previous cohorts before providing 
recommendations related to dose escalation for the subsequent cohort. Recommendations to 
proceed with dose escalation, to modify the dose escalation schema, or modify the protocol 
related to subject oversight will be made by the SRC. 
9.7. 
Prior and Concomitant Medications 
Because toxicities and adverse events experienced by subjects on study can be related not only to 
IP, but also to medications and/or therapies administered immediately prior to or while on study, 
Investigators (or their designee) must record medications and therapies being taken by the 
subject in the 30 days prior to the first administration of IP in the eCRF, and should include the 
concurrent use of all other prescription or over-the-counter medications, or alternative therapies 
taken while the subject is in the study. 
Probody Tx-specific modules will address prohibited medications; however, the following 
guidelines should be used regarding prior and concomitant medications: 
x Systemic (or intrathecal) therapies and/or radiotherapy intended to treat the subject’s 
cancer other than those specified in the Probody Tx-specific Module are not permitted 
while on the study. Subjects who receive anti-cancer therapy (approved or 
experimental) outside of the treatment described in the Module will need to be 
withdrawn from study treatment. 
x Supportive care measures considered standard of care for subjects with the cancers 
specified within the Probody Tx-specific Module, such as growth factors and 
transfusion support, may be permitted while on study. 
x Systemic corticosteroid use at prednisone-equivalent doses > 50 mg/day are not 
permitted while on study, except for the acute treatment of reversible adverse events 
(eg, infusion-related reactions [IRR]) or prophylaxis against IRR. 


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x In the event that a subject develops tumor lysis syndrome, follow institutional 
practices for management and report the event as an SAE. 
Refer to the Probody Tx-specific module for specific recommendations and/or exclusions 
pertaining to concomitant medications. 
9.8. 
Continuation of Study Treatment 
Dosing of the Probody Tx as monotherapy and/or as combination therapy will be permitted for 
subjects meeting the following criteria: 
x Evidence of ongoing clinical benefit: Subject has evidence of objective response, 
improvement in symptoms, or no clinically significant documented progression of 
disease 
x Acceptable safety: subject does not experience DLT or treatment-related adverse 
event that precludes continued treatment with the treatment regimen 
x It is felt to be in the subject’s best interests to continue study treatment, as determined 
by the Investigator and the Medical Monitor 
9.9. 
Withdrawal of Subjects 
9.9.1. 
Withdrawal Criteria 
Probody Tx-specific withdrawal criteria will be defined in the module. In general, subjects may 
choose to withdraw from treatment and/or the study at any time for any reason. The reason 
should be documented in the subject’s medical record and recorded on the appropriate eCRF. 
Subjects may be withdrawn from the study for any of the following reasons:  
x The subject experiences clinically significant disease progression 
x The subject is unwilling or unable to adhere to the protocol 
x The subject withdraws consent or is lost to follow-up 
x The subject experiences an intercurrent illness that prevents further administration of 
IP and/or reference therapy 
x The subject experiences a DLT or an adverse event related to study drug(s) which 
precludes further administration of the study drug(s) 
x The subject experiences a prolonged treatment delay  
x The subject becomes pregnant, either prior to the first dose of study drug or at any 
time during treatment 
x In the investigator’s judgement, the subject should discontinue treatment 
x The Sponsor terminates the study 


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9.9.2. 
Withdrawal from Treatment 
Subjects may discontinue study treatment, but remain in follow-up. Subjects discontinued from 
study treatment due to an AE (whether serious or non-serious), including clinically significant 
abnormal laboratory test values, will be followed for resolution of the event or return to baseline. 
Subjects who discontinue study treatment for reasons other than objective evidence of disease 
progression should be followed to document objective progression after study treatment 
discontinuation, if possible. 
All End of Treatment (EOT) procedures should be completed within 30 (+7) days of the last dose 
of study drug. 
9.9.3. 
Withdrawal from Study 
If it is necessary to withdraw a subject from the study earlier than planned, all End of Study 
(EOS) procedures should be completed. 
9.9.4. 
Replacement of Subjects 
Subjects who withdraw from the study during the DLT evaluation interval for reasons other than 
a DLT will be replaced. 


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10. 
SAFETY, EFFICACY, PK, PD, AND OTHER ASSESSMENTS 
10.1. 
Safety 
Refer to the Schedule of Events within the Module for the timing of tests and procedures. Safety 
will be evaluated by measures that may include those listed below. Additional measures, specific 
to the Probody Tx and/or cancer type, will be specified in the module. 
10.1.1. 
Adverse Events 
AEs will be collected from start of treatment until 30 days after the last dose of study treatment 
(IP or reference therapy), unless otherwise stipulated in the module. 
AEs will be evaluated by classifying and grading all events for severity according to NCI 
CTCAE, v4.03 (see Study Reference Manual) and for relationship to IP. Refer to Section 12 . 
10.1.2. 
Clinical Laboratory Tests 
The Clinical laboratory tests evaluated in the CTMX-C-001 program are listed in the sections 
below. Blood samples may be drawn from an IV access line used for study drug administration 
only if the line has been well flushed of study drug per standard local practice. The schedule for 
laboratory testing will be outlined in the Schedule of Events in each Probody Tx-specific 
Module. 
Safety labs (eg, hematology, serum chemistry, urinalysis) will be performed by local laboratories 
unless otherwise stipulated in the module. Samples for PK, PD and exploratory tests will be 
performed by a central laboratory; collection and processing instructions will be detailed in a 
separate Laboratory Manual. 
10.1.2.1. Hematology 
Hematology samples collected will be evaluated for complete blood count (CBC) with 
differential, including blast count, platelet count, and reticulocyte count. CBC includes red blood 
cells (RBCs), hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular 
hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC), and white blood 
cells (WBCs) with differential count to include neutrophils, eosinophils, basophils, lymphocytes, 
monocytes, and blasts.  
10.1.2.2. Serum Chemistry 
Chemistry samples collected will be evaluated for alkaline phosphatase, aspartate 
aminotransferase (AST) / serum glutamic-oxaloacetic transaminase (SGOT) and alanine 
aminotransferase (ALT) / serum glutamic-pyruvic transaminase (SGPT), total bilirubin, calcium, 
phosphorus, blood urea nitrogen (BUN), creatinine, total protein, albumin, glucose, potassium, 
sodium, chloride, bicarbonate, uric acid, lactate dehydrogenase (LDH), and hemoglobin A1c.  
Blood glucose should be fasting to evaluate possible hyperglycemia (pre-existing, or acquired 
while on study).  
Calculated creatinine clearance may be performed using the Cockcroft-Gault equation.  


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10.1.2.3. Thyroid Function 
Blood for thyroid-stimulating hormone (TSH), Free T4 and T3 will be drawn in studies of 
Probody Tx that may induce an immune response. 
10.1.2.4. Immune Safety Assays 
In studies of Probody Tx that may induce an immune response, testing may include: free T4 and 
T3, rheumatoid factor (RF), adrenocorticotropic hormone (ACTH), C-reactive protein (CRP), 
antinuclear antibody (ANA) titer and pattern.  
The following tests, may also be performed on selected stored samples at a later date: anti-DNA 
antibody, anti-phospholipid antibody, anti-SSA antibody (Ro), anti-islet cell antibody; anti-SSB 
antibody (La), anti-neutrophil cytoplasm antibody, anti-thyroglobulin antibody, C3 and C4, 
anti-LKM antibody, and CH50. 
Abnormal endocrine results should be followed up with prolactin and a.m. cortisol tests, and may 
require an endocrine consult and additional testing. 
10.1.2.5. Coagulation 
Coagulation samples will be evaluated for prothrombin time (PT), partial thromboplastin time 
(PTT), and international normalized ratio (INR). 
10.1.2.6. Urinalysis 
Urinalysis will include assessment of protein, blood, leukocytes, glucose, ketones, bilirubin, 
urobilinogen, pH, and specific gravity, plus microscopic exam. 
10.1.2.7. Pregnancy 
Pregnant women are not eligible for inclusion in the study. A serum pregnancy (human chorionic 
gonadotropin [HCG]) should be evaluated in all WOCBP. Urine pregnancy tests may be 
performed in lieu of serum pregnancy tests while the subject is on treatment. 
10.1.3. 
Other Safety Measures 
10.1.3.1. Vital Signs 
Vital signs will include heart rate and blood pressure (supine), temperature, respiratory rate, and 
pulse oximetry. 
Weight and height will be measured. 
10.1.3.2. Electrocardiogram (ECG) 
12-lead ECGs should be obtained, in triplicate (approximately 2-5 minutes apart), in digital 
format (when possible), and archived, while supine at screening, at time points to be specified in 
the Probody Tx-specific Module.  


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10.1.3.3. Physical Exam 
A complete physical examination includes assessment of the skin, head, eyes, nose, throat, neck, 
joints, lungs, heart, abdomen (including liver and spleen), lymph nodes, and extremities. A brief 
neurological examination should also be performed. A limited, targeted physical exam should be 
performed as needed by subject symptoms or clinical observations, focused on key organ 
systems of interest (eg, cardiovascular [CV], pulmonary, gastrointestinal [GI], skin, ophthalmic, 
or any systems with previously noted abnormal findings).  
10.1.3.4. Ophthalmology Exam 
Where applicable, a complete ophthalmology exam will be performed by a board-certified 
ophthalmologist at baseline, post-treatment and as specified in the Probody Tx-specific module 
and will include visual acuity, indirect fundoscopy, slit lamp examination under dilatation, 
intraocular pressure measurement and corneal photography (not required at baseline). Baseline 
testing will also include Schirmer’s test. Subjects will be asked about ocular symptoms such as a 
history of dry eye and contact lens use and an ocular symptom assessment (blurred vision, ocular 
discomfort, etc) will be performed.  
10.1.3.5. Concomitant Medications/Therapies 
Concomitant medications/therapies will be recorded.  
10.1.3.6. Eastern Cooperative Oncology Group (ECOG) Performance Status 
The ECOG performance status (Appendix 16.1) will be evaluated during the study. 
10.2. 
Efficacy 
Although response is not the primary endpoint of the Phase 1-2 trials conducted under the 
Common Core Document, tumor response will be assessed by standard criteria to obtain a 
preliminary estimate of anti-cancer efficacy for the Probody Tx (as monotherapy and/or as 
combination therapy) in subjects with advanced or unresectable solid tumors. Additional criteria 
specific to a cancer (eg, the Lugano Classification for lymphomas) will be outlined in the 
Probody Tx-specific Module, as applicable. 
Efficacy parameters may include: 
x ORR (RECIST version 1.1 and, as applicable, modified immune-related RECIST 
[irRECIST] criteria) 
x TTR 
x DOR 
x PFS 
x OS 
Efficacy will be assessed by RECIST v1.1 (and modified irRECIST for agents thought be 
immune-active as guided by the drug-specific module), if applicable. 


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10.2.1. 
Imaging 
Computerized (or computed) tomography (CT) with and/or without contrast or magnetic 
resonance imaging (MRI) will be performed as appropriate. Bone scans and positron emission 
tomography (PET) scans may be performed if clinically indicated, but may not be used to 
measure target lesions. Imaging methods will be employed consistently during the course of each 
subject’s evaluation during the study.  
10.2.2. 
Tumor Markers 
Blood draws for tumor makers will be outlined in the module, as applicable. 
10.2.3. 
Response Criteria 
RECIST v1.1 guidelines (Eisenhauer et al, 2009) will be used to evaluate response to therapy. 
Other tumor-specific response criteria will be utilized, as applicable, as well as modified 
irRECIST criteria (Bohnsack et al, 2014) for agents thought to be immuno-active. 
Imaging of the chest, abdomen, and pelvis (as applicable) is required within 30 days prior to the 
first administration of Probody Tx. CT and magnetic resonance imaging (MRI) are acceptable. 
Subjects with skin, subcutaneous or lymph node metastases may also have tumor evaluations 
(including measurements with a ruler) by means of physical examination. During Screening, 
subjects must have disease that is measurable by standard imaging techniques or evaluable, per 
RECIST v1.1. For subjects who have received prior radiation therapy, measurable lesions must 
be outside of any prior radiation field(s), unless disease progression has been documented at that 
disease site subsequent to radiation. 
In subjects for whom a baseline scan indicates no evidence of pelvic malignancy, chest/abdomen 
imaging may be performed (without pelvic imaging) at subsequent evaluations. In selected 
situations, a combination of CT/MRI is acceptable (ie, CT of chest, MRI of abdomen). The same 
imaging modalities used to characterize each site of disease at baseline should be used 
throughout the duration of the study. Imaging of extremities is also permitted and is required if 
significant metastases are present and are optimally evaluated via CT/MRI of an extremity. 
Unless otherwise specified in the Probody Tx-specific Protocol Module Schedule of Events, 
tumor measurements and disease response assessments are to be performed every 8 weeks after 
the first dose of study drug through 12 months of treatment and then every 12 weeks from 
Month 13 until development of progressive disease (PD). Additional assessments may be 
performed during follow-up and will be specified in the Probody Tx-specific Protocol Module. 
Tumor measurements and disease response assessment are to be performed at the EOT visit as 
well. 
Anatomical measurements (summed across target lesions) will be documented. When possible, 
the same qualified physician should interpret results to reduce variability. Radiographic images 
will be maintained at the study center, and Investigator findings will be filed in the subject’s 
source documents. 


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10.2.3.1. RECIST v1.1 
Assessment of Measurable, Non-measurable, Target and Non-Target Lesions 
During Screening, tumor lesions are to be categorized as measurable versus non-measurable and 
target versus non-target, as follows. 
Measurable versus non-measurable 
x Measurable lesions can be accurately measured in at least one dimension (longest 
diameter [LD] to be recorded) with a minimum size of: 10 mm by CT or MRI scan for 
non-QRGDOOHVLRQVDQGPPLQVKRUWD[LVIRUQRGDOOHVLRQV, 10 mm caliper 
measurement by clinical exam, or 20 mm by chest X-ray (CXR).G
x Non-measurable: all other lesions, including small lesions (longest diameter < 10 mm 
RUSDWKRORJLFDOO\PSKQRGHVZLWK 10 to < 15 mm short axis) and truly 
non-measurable lesions (eg, pleural or pericardial effusion, lymphangitic involvement 
of skin or lung).  
Target versus non-target 
x Target: all measurable lesions up to a maximum of 2 lesions per organ and 5 lesions 
in total, representative of all involved organs, are to be identified as target lesions and 
measured and recorded at Screening. Target lesions are to be selected on the basis of 
their size (ie, those with the longest diameter) and suitability for accurate repeated 
measurement. The sum of the longest diameter for all target lesions is to be calculated 
and recorded in the eCRF as the baseline sum longest diameter. Target lesions cannot 
be biopsied at any time during the study.  
x Non-target: all other lesions not classified as target lesions (or sites of disease) are to 
be identified as non-target lesions and are to be recorded in the eCRF. Measurement 
of non-target lesions is not required. 
Disease response in target and non-target lesions will be assessed by the Investigator using 
RECIST v1.1 (Eisenhauer et al, 2009), according to the categories and criteria described in the 
table below. The best overall response for each subject will be reported as the best response 
documented over the sequence of objective statuses recorded using the categories and criteria in 
Table 3.  


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10.2.4. 
Definitions of Treatment Outcomes: RECIST v1.1 
Table 3: 
Response Evaluation Criteria in Solid Tumors (RECIST) Guidelines for 
Tumor Response 
Disease Response Criteria for Target and Non-Target Lesions 
Evaluation of Target lesions 
Complete Response (CR): 
Disappearance of all target lesions. 
Partial Response (PR): 
At least a 30% decrease in the sum of the LD of target lesions, taking 
as reference the baseline sum LD. 
Stable Disease (SD): 
Neither sufficient shrinkage to qualify for PR nor sufficient increase 
to qualify for PD, taking as reference the smallest sum LD since the 
treatment started. 
Progressive Disease (PD): 
At least a 20% increase in the sum of the LD of target lesions, taking 
as reference the smallest sum LD recorded since the treatment started 
or the appearance of one or more new lesions. 
Evaluation of Non-target lesions 
Complete Response (CR): 
Disappearance of all non-target lesions and normalization of tumor 
marker level. 
Incomplete Response/ Stable Disease (SD): 
Persistence of one or more non-target lesion(s) or/and maintenance of 
tumor marker level above the normal limits. 
Progressive Disease (PD): 
Appearance of one or more new lesions and/or unequivocal 
progression of existing non-target lesions.  
Source: Eisenhauer et al, 2009  
Key: LD = longest diameter 


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Table 4: 
Overall Response Criteria (RECIST v1.1) 
Subjects with Target and Non-Target Lesions 
Target Lesions 
Non-Target Lesions 
New Lesions 
Overall 
Response 
CR 
CR 
No 
CR 
CR 
Non-CR / Non-PD 
No 
PR 
CR 
Not evaluated 
No 
PR 
PR 
Non-PD or not all evaluated 
No 
PR 
SD 
Non-PD or not all evaluated 
No 
SD 
Not evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or no 
PD 
Any 
PD 
Yes or no 
PD 
Any 
Any 
Yes 
PD 
Subjects with Non-Target Lesions Only 
Non-Target Lesions 
New Lesions 
Overall 
Response 
CR 
No 
CR 
Non-CR / Non-PD 
No 
Non-CR / 
Non-PD 
Not all evaluated 
No 
NE 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
Source: Eisenhauer et al, 2009  
Key: CR = complete response; NE = not evaluable; PD = progressive disease 
Any subject with a CR or PR is to have repeat assessments performed no earlier than 4 weeks 
later to confirm the response.  
10.2.4.1. Modified immune-related RECIST (irRECIST) 
As noted by Bohnsack et al (2014), RECIST v1.1 has some limitations when applied to 
immunotherapy in oncology. Tumors that appear to have progressed by RECIST criteria may 
later regress, possibly reflective of the impact of immune agents on host antitumor response 
(Chiou & Burotto, 2015).  
Modified irRECIST criteria (Appendix 16.2) will be used to evaluate tumor response. 
Definitions for measurable, non-measurable, target and non-target lesions are outlined in 
Section 10.2.3.1. 


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The Bohnsack et al (2014) modifications of the iRECIST criteria differ from the immune-related 
Response Criteria (irRC) as noted by Wolchock et al (2009) as follows: 
1. At the time of unconfirmed progression, the baseline is reset and the immune-related 
Progressive Disease (irPD) is only achieved if an increase in tumor burden of 20% 
relative to the new baseline is observed.  
2. Target lesions cannot be biopsied at any time during the study. 
Table 5: 
Derivation of modified irRECIST Overall Responses 
TMTB of all measurable and 
new measurable lesions,D% 
Non-target lesions 
New, non-measurable 
lesions 
Overall 
Response 
Reduction of 100 
Absent 
Absent 
irCRȕ 
Reduction of 100 
irNon-CR/Non-PD 
Absent/Stable 
irPR 
Reduction of 100 
Absent/Stable 
irNon-CR/Non-PD 
irPR 
Reduction of t 30 
irNN 
No unequivocal worsening 
irPR 
Reduction of < 30 to < 20 increase 
Absence of unequivocal worsening 
irSD 
t 20 increaseJ 
Any 
Any 
irPDG 
Any 
Unequivocal worsening 
Any 
irPDG 
Any 
Any 
Unequivocal worsening 
irPDG 
Source: Bohnsack et al (2014) 
TMTB = Total Measured Tumor Burden; irCR = immune-related Complete Response; irPR = immune-related 
Partial Response; irSD = immune-related Stable Disease; irPD = immune-related Progressive Disease. irNN = no 
target disease identified at baseline and at follow-up, the subject fails to meet the criteria for irCR or irPD. 
Į Decreases assessed relative to baseline 
ȕ Lymph nodes must also decrease to < 10 mm in short axis. 
G At the time of unconfirmed progression, the baseline is reset and irPD is only achieved if an increase in tumor 
burden of 20% relative to the new baseline is observed. 
J Minimum 5 mm absolute increase in TMTB compared to nadir 
10.2.4.2. Tumor-Specific Response Criteria 
Tumor-specific response criteria will be assessed, as applicable.  


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10.2.4.2.1. Lymphoma Specific Response Criteria  
The Lugano classification as noted by Cheson et al (2014) and Cheson (2015) will be used to 
assess response in lymphomas.  
Measurable versus non-measurable 
x Measurable lesions: Maximum of 6 of the largest dominant nodes, nodal masses, and 
extranodal lesions that can be accurately measured in 2 diameters. Nodes should 
preferably be from disparate regions and include mediastinal and retroperitoneal 
areas, when applicable. Non-nodal lesions include those in solid organsG
x Non-measurable: all other lesions, including nodes, nodal masses, and extranodal 
sites that are abnormal but not selected as dominant as well as truly non-measurable 
lesions (eg, pleural effusions, ascites, bone lesions).  
Table 6: 
Response Criteria for Lymphoma 
Response Criteria 
PET-CT-based response 
CT-based response3 
Complete Response (CR): 
Lymph nodes and 
extralymphatic sites 
Score 1, 2, or 3 with or without a residual 
mass on a PET five point scale (5-PS)1,2 
 
Decrease of target nodes/nodal 
masses to  1.5 cm in LD and no 
extralymphatic sites of disease 
Non-measured lesion 
N/A 
Absent 
Organ enlargement  
N/A 
Decrease in size to normal 
New lesions 
None  
None 
Bone marrow 
No evidence of FDG-avid disease in 
marrow 
Morphology normal; if 
indeterminate, IHC negative 
Partial Response (PR) 
Lymph nodes and 
extralymphatic sites 
Score 4 or 51 with reduced uptake 
compared with baseline and residual 
mass(es) of any size. These findings at 
interim suggest responding disease and at 
End of Treatment indicate residual disease.  
63'GHFUHDVHRI IRU 6 
target measurable nodes and 
extranodal sites. 
When a lesion is too small to 
measure on CT, assign 5 mm x 5 
mm as default value.  
Non-measured lesion 
N/A 
No increase; either absent/normal or 
regressed 
Organ enlargement  
N/A 
Spleen regressed by > 50% in length 
beyond normal 
New lesions 
None  
None 
Bone marrow 
Residual uptake higher than uptake in 
normal marrow but decreased relative to 
baseline. If there are persistent focal 
changes in the marrow in the setting of a 
nodal response then consider further 
evaluation by MRI or biopsy or interval 
scan. 
N/A 


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Response Criteria 
PET-CT-based response 
CT-based response3 
No Response or Stable Disease (SD) 
Target nodes/nodal masses, 
extranodal lesions  
No response with score 4 or 51 with no 
significant change in FDG uptake from 
baseline at interim or End of Treatment. 
SPD decrease of < 50% from 
EDVHOLQHIRUGRPLQDQW
measureable nodes and extranodal 
sites 
Non-measured lesion 
N/A 
No increase consistent with 
progression 
Organ enlargement  
N/A 
No increase consistent with 
progression 
New lesions 
None  
None 
Bone marrow 
No change from baseline 
N/A 
Progressive Disease (PD) 
Individual target 
nodes/nodal masses, 
extranodal lesions  
Score 4 or 51 with increase in uptake 
intensity from baseline and/or new FDG-
avid foci consistent with lymphoma at 
interim or End of Treatment. 
Individual node that is abnormal 
with LD > 1.5cm and increase of 
 50 from PPD nadir. Increase in 
LDi or SD by 0.5cm from nadir for 
OHVLRQVFPRU cm for lesions 
> 2cm.  
New or recurrent splenomegaly. 
In the setting of splenomegaly, the 
splenic length must increase by 
> 50% of the extent of its prior 
increase beyond baseline (ie, 15 cm 
spleen must increase to > 16 cm). If 
no prior splenomegaly, then must 
LQFUHDVHE\ 2 cm from baseline.  
Non-measured lesion 
None 
New or clear progression of 
pre-existing non-measured lesions.  
New lesions 
New FDG-avid foci consistent with 
lymphoma and not another etiology. If 
uncertain regarding etiology, can consider 
biopsy or interval scan. 
Regrowth of previously resolved 
lesions or new node > 1.5 cm or 
new extranodal site > 1.0 cm if any 
axis if < 1.0 cm in any axis that is 
unequivocally attributable to 
lymphoma. 
Bone marrow 
New or recurrent FDG avid foci 
New or recurrent involvement 
Source: Cheson 2015 
Key: SPD = sum of the product of the perpendicular diameters for multiple lesions; LDi = longest transverse 
diameter of a lesion; SDi = shortest axis perpendicular to the LDi; PPD = cross product of the LDi and perpendicular 
diameter. 
1 PET 5 Point Scale (36 QRXSWDNHDERYHEDFNJURXQG XSWDNHPHGLDVWLQXP XSWDNH!PHGLDVWLQXPEXWOLYHU
4= uptake moderately > liver; 5 = uptake markedly higher than liver and/or new lesions; X = new areas of uptake unlikely to be 
related to lymphoma 
2 “Waldeyer’s ring or extranodal sites with high physiological uptake or with activation within spleen or marrow, eg, with 
chemotherapy or myeloid colony stimulating factors, uptake could be greater than normal mediastinum and/or liver. In this 
context, complete metabolic response (CMR) may be inferred if uptake at sites of initial involvement is no greater than 
surrounding normal tissue even if the tissue has high physiological uptake.” 


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10.3. 
Pharmacokinetics 
Detailed instructions for pharmacokinetic, immunogenicity, pharmacodynamics and exploratory 
immune function evaluations will be provided in the Laboratory Manual. 
Serial blood samples to characterize the PK of the Probody Tx will be collected only in subjects 
enrolled to the dose-finding cohorts. The entire PK sampling scheme, including time points for 
collection, will be provided in each Probody Tx-specific Module.  
PK parameters that will be measured, calculated, and reported may include the following: 
maximum plasma concentration (Cmax), minimum plasma concentration (Cmin), half-life (T½), 
clearance (CL), steady state volume of distribution (Vss), time to reach Cmax (tmax), and area under 
the curve zero to infinity (AUC0-inf). 
10.4. 
Immunogenicity 
Serum samples will be collected to assess the extent of ADA response to Probody Txs. Incidence 
and titer of anti-Probody Tx antibodies will be defined based on samples obtained prior to the 
first dose and as specified in the Probody Tx-specific module. 
10.5. 
Pharmacodynamics 
Exploratory assays measuring target expression and PD parameters that potentially could be used 
either to select subjects suitable for treatment, or to predict response to treatment with a Probody 
Tx, will be performed on blood and/or tissue samples. The specific assays will be specified in the 
Probody Tx-specific Module. 
10.6. 
Exploratory Immune Function Evaluations 
Exploratory immune function evaluations may be conducted in subjects treated with a Probody 
Tx. Exploratory immune function evaluations will be defined in the Probody Tx-specific module. 
The Probody Tx-specific Modules will specify the sample collection time points for blood and/or 
tissue samples, including optional research samples collected and stored for future research 
which may include disease-related biomarkers (or antibody responses to selected antigens), 
exploratory humoral and cellular immune responses to tumor antigens and a panel of recall 
non-tumor antigens. Available slides and tissue samples from tumor biopsies collected before 
enrollment may also be examined for tumor makers and inflammatory infiltrates. 
Optional research-related tumor or other biopsies (eg, inflamed tissue) that do not require general 
anesthesia may be obtained with the subject’s explicit consent to assess morphology and the 
presence or absence of inflammatory infiltrates, and their cellular characterization. 


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11. 
STATISTICAL PLAN AND ANALYSIS 
Analyses common to the modules are described in the Common Core Document. Analyses 
specific to a Protocol Module will be described in a module-specific statistical analysis plan 
(SAP). 
Descriptive summaries will be provided. For continuous measures, these include mean, median, 
standard deviation, and range. For categorical measures, these include counts and percentages. 
The safety analysis population includes all enrolled subjects who receive at least one dose of 
study drug. The safety analysis population is used for evaluating subject characteristics, 
treatment administration, safety endpoints, and efficacy analyses related to PFS and OS. 
The response evaluable population includes all subjects in the safety analysis population who 
have an adequate baseline disease assessment. The response-evaluable population is used for 
efficacy analyses related to objective response, including objective response rate (ORR), TTR, 
and DOR.  
Analyses may be presented by cancer type, treatment regimen, and dose, when applicable.  
11.1. 
Demographic and Baseline Characteristics 
Descriptive statistics will be generated for all demographic and baseline characteristics. 
11.2. 
Safety Analysis 
Adverse events will be coded in accordance with the medical dictionary for regulatory activities 
(MedDRA) Version 16.1. Only treatment-emergent adverse events occurring and reported during 
the study period will be included in the adverse event summaries. A treatment-emergent AE is an 
event that emerges during treatment having been absent pre-treatment, or worsens relative to the 
pre-treatment state. AE presentation will include incidence, severity (categorized by NCI 
CTCAE criteria), and relationship to study drug.  
Dose-limiting toxicities, study-drug related AEs, and AEs leading to discontinuation will be 
listed. In addition, changes from baseline in clinical laboratory results and vital signs will be 
assessed. ECGs and immunogenicity tests may be summarized using descriptive statistics, when 
applicable. 
11.3. 
Efficacy Analysis 
ORR is the primary efficacy endpoint. For solid tumors, response evaluation will be based on the 
RECIST criteria (v1.1) and ORR is defined as the proportion of subjects with complete response 
(CR) or partial response (PR) on two consecutive tumor assessments at least 4 weeks apart 
according to RECIST (RECIST v1.1). In addition, immune-related RECIST (irRECIST) criteria 
will also be used for Probody therapeutics that are likely to be immunostimulating. For 
lymphoma, objective response will be based on tumor-specific criteria.  
The secondary efficacy endpoints include duration of response (DOR), TTR, progression-free 
survival (PFS), and overall survival (OS). 


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TTR is defined as the time from the date of the first dose of study drug to first documentation of 
objective tumor response. TTR is only calculated for subjects in the response-evaluable 
population who have a confirmed objective tumor response. 
DOR is defined as the time from the first documentation of objective tumor response that is 
subsequently confirmed to the first documentation of objective disease progression or death due 
to any cause, whichever occurred first. DOR is only calculated for subjects in the 
response-evaluable population who have a confirmed objective tumor response. Subjects who 
neither progress nor die will be censored on the date of their last tumor assessment. 
PFS is defined as the time from the date of the first dose of study drug to the date of first 
documentation of objective tumor progression or death due to any cause, whichever occurs first. 
Subjects who die without a reported progression will be considered to have progressed on the 
date of their death. Subjects who did not progress or die will be censored on the date of their last 
tumor assessment. Subjects who did not have any on-study tumor assessments and did not die 
will be censored on their date of enrollment/randomization (as applicable). Subjects who started 
anti-cancer therapy without a prior reported progression will be censored on the date of their last 
tumor assessment prior to the initiation of subsequent anti-cancer therapy. 
OS is defined as the time from the date of the first dose of study drug to the date of death due to 
any cause. All deaths will be included in the analysis. 
11.3.1. 
Efficacy Analysis Methods 
The primary efficacy endpoint is the ORR and the primary efficacy analysis is based on the 
response-evaluable population. Exact 2-sided 95% confidence intervals will be calculated for all 
proportion estimates. Estimates of time-to-event endpoints (DOR, PFS, and OS) will be obtained 
using the Kaplan-Meier method. DOR and TTR will also be summarized using descriptive 
statistics for confirmed objective responders 
11.4. 
Pharmacokinetic Analysis 
A compartmental analysis will be performed to characterize the PK. A model with a number of 
compartments consistent with the data will be fit to each subject’s data using nonlinear least 
squares regression. The model will be parameterized in terms of the primary parameters, the 
clearance(s) (CL) and Vss. Secondary parameters—Cmax, Cmin, Vss, distribution and elimination 
rate constants and T½ (if a multi-compartmental model), and AUC (inf)—will be calculated from 
the primary parameters. 
Individual subject plasma concentrations, actual blood sampling times, and PK parameters will 
be listed by dose cohort. Plasma concentrations and PK parameters will be summarized using 
descriptive statistics. Individual subject observed and model-predicted plasma concentrations and 
mean observed plasma concentrations will be displayed graphically on linear and 
semi-logarithmic axes. These data may also be used in a future population PK analysis.  
11.5. 
Immunogenicity 
Blood samples for immunogenicity analysis will be collected from all subjects enrolled and 
evaluated for the development of ADA response. 


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11.6. 
Exploratory Analysis 
Data may be pooled across modules to study properties common to Probody platform. 
11.7. 
Determination of Sample Size 
The sample size of each module is determined by the module objectives. The justification for the 
sample size will be provided in the Probody Tx-specific module.  
11.8. 
Interim Analysis 
No formal interim analysis is planned. 
Administrative interim analyses on safety and efficacy or on PK, immunogenicity, and selected 
biomarkers may be performed several times prior to completion of the study in order to facilitate 
program decisions and to support study presentations or publications. 
11.9. 
Deviation from Original Analysis Plan 
All deviations from the original SAP will be provided in the final CSR.  


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12. 
ADVERSE EVENTS 
All AE definition and reporting information will be provided in the Probody Tx-specific module.  


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13. 
ETHICS 
All ethical review and conduct including subject information and informed consent will be 
provided in the Probody Tx-specific module. 


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14. 
STUDY ADMINISTRATION 
14.1. 
Administrative Structure 
A list of individuals who will have key positions in this study will be saved in the 
Module-specific Trial Master File (TMF). This list will include names, titles, and roles of 
selected individuals from the Sponsor and the Contract Research Organization(s) (CRO[s]) that 
will contribute to the study. 
14.2. 
Quality Control and Quality Assurance 
14.2.1. 
Overview 
Quality assurance (QA) and quality control (QC) systems with written standard operating 
procedures (SOPs) will be implemented and maintained to ensure that the study will be 
conducted and data will be generated, documented (recorded), and reported in compliance with 
the protocol, GCP, and the applicable regulatory requirements. 
QC will be applied to each stage of data handling. To ensure the accuracy, consistency, 
completeness, and reliability of the data, the study will include a combination of the following: 
x Investigator meeting(s), 
x Site initiation visit, 
x Routine site monitoring, 
x Ongoing site communication and training, 
x Data management quality control checks, 
x Continuous data acquisition and cleaning, 
x Internal review of data, and 
x QC checks of the final CSR. 
During and/or after completion of the study, quality assurance personnel named by CytomX or 
the regulatory authorities may wish to perform on-site audits. The Investigator is expected to 
cooperate with any audit and provide assistance and documentation (including source data) as 
requested.  
In addition, the CytomX (or designee) Clinical QA Department may conduct periodic audits of 
the study processes, including, but not limited to vendors, clinical database, and final CSR. 
14.2.2. 
Monitoring 
The Sponsor has engaged the services of a CRO to perform all monitoring functions for this 
clinical study. Monitors will work in accordance with Sponsor and CRO SOPs and have the 
same rights and responsibilities as monitors from the Sponsor organization. Monitors will 
establish and maintain regular contact between the Investigator or designee and the Sponsor. 


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Monitors will evaluate the competence of each study site, informing the Sponsor about any 
problems relating to facilities, technical equipment or study personnel. During the study, 
monitors will check that written informed consent/assent has been obtained from all subjects 
correctly and that data are recorded correctly and completely in the eCRFs. Monitors are also 
required to compare entries in eCRFs with corresponding source data and to inform the 
Investigator or designee of any errors or omissions. Monitors will also review adherence to the 
protocol and to regulatory requirements at the study site and will discuss deviations noted with 
the Investigator or designee. They will arrange for the study site to receive adequate supply of IP 
and ensure appropriate storage conditions are maintained. 
Monitoring visits will be conducted according to the US CFR Title 21 parts 50, 56, and 312 and 
ICH Guideline for GCP. The monitor will make written reports to the Sponsor following each 
contact with the Investigator or designee, regardless of whether it is by phone or in person. 
14.2.3. 
Data Management/Coding 
Study data will be handled according to the relevant SOPs of the data management and 
biostatistics departments of the Sponsor or CRO. 
AEs will be coded using MedDRA and medications will be coded using WHO Drug Dictionary 
Enhanced (WHO DDE) drug dictionary. 
14.2.4. 
Quality Assurance Audit 
Study sites, the study database and study documentation may be subject to a QA audit during the 
course of the study, conducted by the Sponsor or designee on behalf of the Sponsor. In addition, 
inspections may be conducted by regulatory bodies at their discretion. 
14.3. 
Data Handling and Recordkeeping 
14.3.1. 
Electronic Data 
When using electronic trial data handling and/or remote electronic trial data systems, the Sponsor 
will: 
a. Ensure and document that the electronic data processing system(s) conforms to the 
Sponsor’s established requirements for completeness, accuracy, reliability, and 
consistent intended performance (ie, validation). 
b. Maintain SOPs for using these systems. 
c. Ensure that the systems are designed to permit data changes in such a way that the 
data changes are documented and that there is no deletion of entered data 
(ie, maintain an audit trail, data trail, edit trail). 
d. Maintain a security system that prevents unauthorized access to the data. 
e. Maintain a list of the individuals who are authorized to make data changes. 
f. Maintain adequate backup of the data. 
g. Safeguard the blinding, if any (eg, maintain the blinding during data entry and 
processing). 
Documentation regarding electronic systems used in this protocol is located in the Data 
Management Plan. 


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14.3.2. 
Case Report Form Completion 
Electronic data capture will be used for the study. Data will be recorded on source 
documentation at each study location and entered into the eCRF electronically by the study 
center personnel for each study subject. Data collected on each subject will be documented on 
the appropriate eCRF. Completed eCRFs are to be reviewed and electronically signed by the 
Investigator or his/her designee. 
It is the Investigator’s responsibility to ensure the accuracy, completeness and timeliness of the 
data reported in the subject’s eCRF. Source documentation supporting the eCRF data should 
indicate the subject’s participation in the study and should document the dates and details of 
study procedures, AEs, and subject status. 
For subjects who discontinue or terminate from the study, the eCRFs will be completed as much 
as possible, and the reason for the discontinuance or termination clearly and concisely specified 
on the appropriate eCRF.  
A copy of the completed eCRFs and associated queries and audit trail for subjects enrolled at the 
site will be provided at the completion of the study for retention. 
14.3.3. 
Data Handling 
If data are transformed during processing, records will be maintained so that it will be possible to 
compare the original data and observations with the processed data. 
An unambiguous subject identification (ID) code will be used that allows ID of all the data 
reported for each subject. 
14.3.4. 
Retention of Study Records 
The Investigator must maintain essential study documents (protocol and protocol amendments, 
completed eCRFs, signed ICFs, relevant correspondence, and all other supporting 
documentation) until at least 2 years after the last approval of a marketing application in an ICH 
region and until there are no pending or contemplated marketing applications in an ICH region or 
at least 2 years after the formal discontinuation of clinical development of the IP. These 
documents will be retained for a longer period if required by the applicable regulatory 
requirements or the hospital, institution, or private practice in which the study is being 
conducted. Subject ID codes (subject names and corresponding study numbers) will be retained 
by the site for this same period of time. These documents may be transferred to another 
responsible party, acceptable to the Sponsor, who agrees to abide by the retention policies. 
Written notification of transfer must be submitted to the Sponsor. The Investigator or designee 
must contact the Sponsor prior to disposing of any study records. 
14.4. 
Financing and Insurance 
Financing and insurance are addressed in a separate document. 
14.5. 
Confidentiality 
To maintain subject privacy, all eCRFs, study drug accountability records, study reports and 
communications will identify the subject by the assigned subject number. The Investigator will 


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grant monitor(s) and auditor(s) from the Sponsor or its designee and regulatory authority(ies) 
access to the subject’s original medical records for verification of data gathered on the eCRFs 
and to audit the data collection process. The subject’s confidentiality will be maintained and will 
not be made publicly available to the extent permitted by the applicable laws and regulations. 
Subjects will be notified that registration information, results, and other information about this 
study will be submitted to ClinicalTrials.gov, a publicly available trial registry database; 
however, protected health information of individual subjects will not be used. 
All information regarding the IP supplied by the Sponsor to the Investigator is privileged and 
confidential information. The Investigator agrees to use this information to accomplish the study 
and will not use it for other purposes without consent from the Sponsor. It is understood that 
there is an obligation to provide the Sponsor with complete data obtained during the study. The 
information obtained from the clinical study will be used toward the development of the IP and 
may be disclosed to regulatory authority(ies), other Investigators, corporate partners, or 
consultants as required. 
14.6. 
Publication Policy 
All information concerning Probody Txs is considered confidential and shall remain the sole 
property of the Sponsor. The Investigator agrees to use this information only in conducting the 
study and shall not use it for any other purposes without written approval from the Sponsor. No 
publication or disclosure of study results will be permitted except as specified in a separate, 
written agreement between Sponsor and the Investigator. 
14.7. 
Direct Access to Source Data 
The Investigators and their respective institutions will allow the Sponsor (or designee), and 
authorized regulatory authorities to have direct access to all documents pertaining to the study 
for study-related monitoring, audits, IRB/IEC review, and regulatory inspections as requested by 
FDA (or other regulatory authorities), the Sponsor, or the Sponsor designee. Direct access to 
records such as source data/documents (ie, original medical records, laboratory reports, hospital 
documents, progress reports, signed informed consent forms, etc) in addition to case report forms 
(CRFs) will be permitted. 
The Investigator or designee will prepare and maintain adequate and accurate source documents 
to support all observations and other pertinent data recorded in the eCRF for each subject 
enrolled into the study. 
14.8. 
Protocol Amendments 
Changes to the conduct of the study will be provided in the Probody Tx-specific module. 


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15. 
REFERENCES 
Annunziata CM, Kohn EC, LoRusso P, Houston ND, Coleman RL, et al. Phase 1, open-label 
study of MEDI-547 in patients with relapsed or refractory solid tumors. Invest New Drugs. 2013 
Feb;31(1):77-84. PubMed PMID: 22370972. 
Bohnsack O, Hoos A, Ludajic K. Adaptation of the Immune Related Response Criteria: 
irRECIST. Ann Oncol. 2014;25(4):iv361-iv372. 
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, et al. Recommendations for 
initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the 
Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. PubMed PMID: 25113753. 
Cheson BD. Staging and response assessment in lymphomas: the new Lugano classification. 
Chin Clin Oncol. 2015 Mar;4(1):5. PubMed PMID: 25841712. 
Chiou VL, Burotto M. Pseudoprogression and Immune-Related Response in Solid Tumors. J 
Clin Oncol. 2015 Nov 1;33(31):3541-3. PubMed PMID: 26261262. 
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, et al. New response evaluation 
criteria in solid tumours: revised RECIST guideline (version 11). Eur J Cancer. 2009 
Jan;45(2):228-47. PubMed PMID: 19097774. 
Lutterbuese R, Raum T, Kischel R, Hoffmann P, Mangold S, et al. T cell-engaging BiTE 
antibodies specific for EGFR potently eliminate KRAS- and BRAF-mutated colorectal cancer 
cells. Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12605-10. PubMed PMID: 20616015. 
Wolchok JD, Hoos A, O'Day S, Weber JS, Hamid O, et al. Guidelines for the evaluation of 
immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 
2009 Dec 1;15(23):7412-20. PubMed PMID: 19934295. 


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16. 
APPENDICES 
16.1. 
ECOG Performance Status 
ECOG PERFORMANCE STATUS 
Grade 
ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction. 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature, eg, light house work, office work. 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. Up 
and about more than 50% of waking hours. 
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of waking 
hours. 
4 
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair. 
5 
Dead  


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16.2. 
Modified Immune Related Response Evaluation Criteria in Solid 
Tumors Guidelines for Tumor Response  
 Definitions 
Modified irRECIST Criteria 
1.0 Baseline: Measurable 
Lesion Definitions and Target 
Lesion Selection1 
Follow the definitions from RECIST v1.1. 
Measurable lesions must be accurately measured in at least one dimension 
with a minimum size of: 
10 mm in the longest diameter by CT or MRI scan (or no less than double 
the slice thickness) for non-QRGDOOHVLRQVDQGPPLQVKRUWD[LVIRUQRGDO
lesions 
10 mm caliper measurement by clinical exam 
20 mm by chest X-ray 
1.1. Baseline: Non-measurable 
Lesion Definitions2 
Follow the definitions from RECIST v1.1. 
Non-target lesions will include: 
Measurable lesions not selected as target lesions 
All sites of non-measurable disease, such as neoplastic masses that are too 
small to measure because their longest uninterrupted diameter is < 10 mm 
(or < two times the axial slice thickness), ie, the longest perpendicular 
GLDPHWHULV 10 and < 15 mm. 
Other types of lesions that are confidently felt to represent neoplastic tissue, 
but are difficult to measure in a reproducible manner. These include bone 
metastases, leptomeningeal metastases, malignant ascites, pleural or 
pericardial effusions, ascites, inflammatory breast disease, lymphangitis 
cutis/pulmonis, cystic lesions, ill-defined abdominal masses, skin lesions, 
etc. 
1.2 Baseline: Target and Non-
Target Lymph Node Lesion 
Definitions 
Follow the definitions from RECIST v1.1. 
1.3 Baseline: Non-Target Lesion 
Selection 
All lesions or sites of disease not recorded as target lesions should be 
recorded as non-target lesions at baseline. There is no limit to the number of 
non-target lesions that can be recorded at baseline. 
1.4 Baseline: Bone Lesions 
Follow the definitions from RECIST v1.1. 
Regardless of the imaging modality blastic bone lesions will not be selected 
as target lesions. Lytic or mixed lytic-blastic lesions with a measurable soft 
tissue component  10 mm can be selected as target lesions. 
1.5 Baseline: Brain Lesions 
Brain lesions detected on brain scans can be considered as both target or 
non-target lesions. 
1.6 Baseline: Cystic and 
Necrotic Lesions as Target 
Lesions 
Lesions that are partially cystic or necrotic can be selected as target lesions. 
The longest diameter of such a lesion will be added to the Total Measured 
Tumor Burden (TMTB) of all target lesions at baseline. If other lesions with 
a non-liquid/non-necrotic component are present, those should be preferred. 
1.7 Baseline: Lesions With 
Prior Local Treatment 
During target lesion selection the radiologist will consider information on 
the anatomical sites of previous intervention (eg, previous irradiation, 
RF-ablation, TACE, surgery, etc). Lesions undergoing prior intervention 
will not be selected as target lesions unless there has been a demonstration 
of progress in the lesion. 


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 Definitions 
Modified irRECIST Criteria 
1.8 Baseline: No Disease at 
Baseline 
If a patient has no measurable and no non-measurable disease at baseline the 
radiologist will assign “No Disease” (irND) as the overall tumor assessment 
for any available follow-up time points unless new measurable lesions are 
identified and contribute to the TMTB. 
2.0 Follow-up: Recording of 
Target and New Measureable 
Lesion Measurements3 
The longest diameters of non-nodal target and new non-nodal measurable 
lesions, and short axes of nodal target and new nodal measurable lesions will 
be recorded. Together they determine the TMTB at follow-up. 
2.1 Follow-up: Definition of 
Measurable New Lesions4 
,QRUGHUWREHVHOHFWHGDVQHZPHDVXUDEOHOHVLRQVOHVLRQVSHURUJDQ
 5 lesions total, per timepoint), new lesions must meet criteria as defined 
for baseline target lesion selection and meet the same minimum size 
requirements of 10 mm in long diameter and minimum 15 mm in short axis 
for new measurable lymph nodes. New measurable lesions shall be 
prioritized according to size, and the largest lesions shall be selected as new 
measured lesions. 
2.2 Follow-up: Non-Target 
Lesion Assessment5 
The RECIST v1.1 definitions for the assessment of non-target lesions apply. 
The response of non-target lesions primarily contributes to the overall 
response assessments of irCR and irNon-CR/Non-PD (irNN). Non-target 
lesions do not affect irPR and irSD assessments. Only a massive and 
unequivocal worsening of non-target lesions alone, even without progress in 
the TMTB is indicative of irPD. 
2.3 Follow-up: New Non-
Measurable Lesions Definition 
and Assessment6 
All new lesions not selected as new measurable lesions are considered new 
non-measurable lesions and are followed qualitatively. Only a massive and 
unequivocal progression of new non-measurable lesions leads to an overall 
assessment of irPD for the timepoint. Persisting new non-measurable lesions 
prevent irCR. 
2.4 irRC Overall Tumor 
Assessments7.8 
irCR, complete disappearance of all measurable and non-measurable 
lesions. Lymph nodes must decrease to < 10 mm in short axis. Confirmation 
of response is not mandatory. 
irPRGHFUHDVHRILQ707%UHODWLYHWREDVHOLQHQRQ-target lesions 
are irNN, and no unequivocal progression of new non-measurable lesions.  
irSD, failure to meet criteria for irCR or irPR in the absence of irPD. 
irNN, no target disease was identified at baseline and at follow-up the 
patient fails to meet criteria for irCR or irPD. 
irPD9, minimum 20% increase and minimum 5 mm absolute increase in 
TMTB compared to nadir, or irPD for non-target or new non-measurable 
lesions. Confirmation of progression is recommended minimum 4 weeks 
after the first irPD assessment. 
irNE, used in exceptional cases where insufficient data exists. 
irND, in adjuvant setting when no disease is detected. 
Source: Bohnsack et al, 2014 
Key: TMTB = Total Measured Tumor Burden; irCR = immune-related Complete Response; irPR = immune-related 
Partial Response; irSD = immune-related Stable Disease; irNN = irNon-CR/Non-PD. irPD = immune-related 
Progressive Disease; irNE = immune-related not evaluable; irND = immune- related no measurable/non-measurable 
disease. 
1Up to 5 target lesions may be selected at baseline. Lesions will be measured unidimensionally. The minimum target 
lesion size at baseline in irRECIST is aligned with RECIST v1.1. 


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2Although irRC does not specifically define non-target lesions, irRC is derived from WHO criteria and indicates 
accordance with the same for the purposes of definitions of non-target lesions. Further clarifications in alignment 
with RECIST v1.1 are provided. 
3Unidimensional measurements are used. Measurements of all measured lesions (baseline-selected target lesions and 
new measurable lesions) are combined into TMTB at follow-up. 
4Larger lesions must be preferred as new measurable over smaller lesions, because there will be a greater impact of 
the TMTB %-increase by these larger lesions for irPD, to support a most conservative approach. 
5Non-target lesions have a subordinate function. In the event that non-target lesions massively progress one cannot 
ignore such worsening and in these rare cases irPD based only on non-target lesions will be a valid assessment 
option. 
6When new non-measurable lesions substantially worsen in these rare cases irPD based only on new non-measurable 
lesions will be an assessment option. 
7The irRECIST overall tumor assessment is based on TMTB of measured target and new lesions, non-target lesion 
assessment and new non-measurable lesions. 
8The thresholds for irPR and irPD assessment are aligned with RECIST v1.1, and confirmation of response is not 
required. 
9An irPD confirmation scan may be recommended for patients with a minimal TMTB %-increase over 20% and 
especially during the flare time-window of the first 12 weeks of treatment, depending on the compound efficacy 
expectations, to account for expected delayed response. 


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16.3. 
Lugano Classification for Lymphomas 
Refer to the Cheson et al (2014) publication on the Lugano Classification for detailed 
recommendations regarding response assessment in lymphoma. Table 3 provides detailed 
information on the revised criteria for response assessment. Highlights of the reference are 
provided below (http://jco.ascopubs.org/content/32/27/3059.long). 
16.3.1. 
Recommendations for Revisions to Staging Criteria 
The recommendations below are intended for lymphomas with primarily nodal involvement. 
Imaging 
 
Based on consensus criteria, PET-CT is recommended for routine stating of fluorodeoxyglucose 
(FDG)-avid, nodal lymphomas. CT scan is preferred in the other lymphomas.  
Tumor Bulk 
A single nodal mass, in contrast to multiple smaller nodes, of 10 cm or greater than a third of the 
transthoracic diameter at any level of thoracic vertebrae as determined by CT is retained as the 
definition of bulky disease for Hodgkin Lymphoma (HL). A CXR is not required to determine 
bulk. The Lugano Classification recommendation for HL and Non-Hodgkin Lymphoma is to 
record the longest measurement by CT scan, with the term X no longer necessary. 
Spleen Involvement 
A single measurement that correlates well with volume is preferable to a volumetric 
measurement or estimation by equations. The Lugano Classification recommends a cutoff for 
splenomegaly of > 13 cm. 
Liver Involvement 
Liver size by physical examination or CT scan is not a reliable measure of hepatic involvement 
by lymphoma. Diffusely increased or focal uptake, with or without focal or disseminated 
nodules, supports liver involvement. 
Bone Marrow Involvement 
For histologies other than diffuse large B-cell lymphoma (DLBCL), follow standard practice and 
perform a 2.5-cm unilateral bone marrow biopsy (BMB), along with immunohistochemistry and 
flow cytometry. 
In DLBCL, a PET-CT scan indicating bone or marrow involvement is usually sufficient to 
designate advanced-stage disease and a BMB is not required. 
16.3.2. 
Assessment of Response  
x PET-CT should be used for response assessment in FDG-avid histologies, using the 
5-point scale; CT is preferred for low or variable FDG avidity. 
x A complete metabolic response (CMR) even with a persistent mass is considered a 
complete remission. 


Common Core Document: CTMX-C-001 
Amendment 02 
 
11 May 2018 
58 of 58 
 
 
x A PR requires a decrease by more than 50% in the sum of the product of the 
perpendicular diameters of up to six representative nodes or extranodal lesions. 
x Progressive disease by CT criteria only requires an increase in the PPDs of a single 
QRGHE\ 
x Surveillance scans after remission are discouraged, especially for DLBCL and HL, 
although a repeat study may be considered after an equivocal finding after treatment. 
Judicious use of follow-up scans may be considered in indolent lymphomas with 
residual intra-abdominal or retro-peritoneal disease. 


CX-2009
Clinical Module CTMX-M-2009-001
CytomX Therapeutics, Inc.
Confidential and Proprietary
Page 123 of 160
Amendment 7, 20 February 2020
Appendix B:
Schedule of Procedures
Table 13.
Schedule of Procedures: Parts A, A2, and B
Table 14.
Schedule of Procedures: Parts C1 and C2
Table 15.
Schedule of Procedures: Parts D1 and D2
Table 16.
Schedule of Procedures: Parts E1 and E2
Table 17.
Schedule of Vital Signs Measurements: All Parts
Table 18.
Schedule of PK and ADA Assessments: Parts A and A2
Table 19.
Schedule of PK and ADA Assessments: Part B
Table 20.
Schedule of PK and ADA Assessments: Part C1
Table 21.
Schedule of PK and ADA Assessments: Parts C2
Table 22.
Schedule of PK and ADA Assessments: Part D1
Table 23.
Schedule of PK and ADA Assessments: Part D2
Table 24.  
Schedule of PK and ADA Assessments: Part E1
Table 25.  
Schedule of PK and ADA Assessments: Part E2


CX-2009
Clinical Module CTMX-M-2009-001
CytomX Therapeutics, Inc.
Confidential and Proprietary
Page 124 of 160
Amendment 7, 20 February 2020
Table 13.
Schedule of Procedures: Parts A, A2, and B
Page 1 of 4
Period/
Procedure
Screening
Treatment Period
FU/EOS 25
Cycle 1 DLT Assessment
Day 1 to Day 21
Cycle 2
Cycle 3 & On 22
EOT 24
Study/Visit Day 1
–30 to 0
1
4 23
(r1d)
8
(r2d)
15
(r2d)
1
(r2d)
8
(r2d)
15
(r2d)
1
(r2d)
8
(r2d)
15
(r2d)
(r7d)
Refer to 
Footnote
Informed consent
X
Medical history 2
X
Demographics
X
AE assessment 3
X
X
X
X
X
X
Concomitant medications 4
X
X
X
X
X
X
X
HIV/CMV/
Hepatitis B, C
X
CX-2009 administration 5
X
X
X
CT/MRI (chest, abdomen, 
pelvis) 6
CT/MRI/Tumor assessment to be conducted every 8 (r1) weeks from the first dose of CX-2009 with assessment for response per
RECIST Version 1.1
Bone scan 7
As clinically indicated
ECG 8
X
Day 1 of Cycles 1 and 3 and as clinically indicated for other visits
X
Full physical examination 9
X
X
Targeted physical 
examination 10
X
X
X
X
X


CX-2009
Clinical Module CTMX-M-2009-001
CytomX Therapeutics, Inc.
Confidential and Proprietary
Page 125 of 160
Amendment 7, 20 February 2020
Table 13.
Schedule of Procedures: Parts A, A2, and B
See footnotes on the following page.
Page 2 of 4
Period/
Procedure
Screening
Treatment Period
FU/EOS 25
Cycle 1 DLT Assessment
Day 1 to Day 21
Cycle 2
Cycle 3 & On 22
EOT 24
Study/Visit Day 1
–30 to 0
1
4 23
(r1d)
8
(r2d)
15
(r2d)
1
(r2d)
8
(r2d)
15
(r2d)
1
(r2d)
8
(r2d)
15
(r2d)
(r7d)
Refer to 
footnote
Complete ophthalmology 
examination 11
X
All subjects within 5 days prior to Cycle 1, Day 1; Cycle 2, Day 1; Cycle 3, Day 1; and at the EOT Visit. Subjects 
who report treatment-emergent changes in vision or other ocular symptoms will undergo repeat examinations 
prior to infusion every other cycle and as clinically indicated.
Ocular symptom assessment 12
X
X
X
X
X
Vital signs
Refer to Table 17
ECOG performance status 13
X
X
X
X
X
Hematology 14
X
X
X
X
X
X
X
X
X
X
X
Serum chemistry 15,16
X
X
X
X
X
X
X
X
X
X
X
Coagulation 17
X
As clinically indicated
X
Urinalysis 18
X
X
Pregnancy test 19
X
X
X
X
X
X
Archival/baseline tumor biopsy
X
Tumor markers 20
As clinically indicated
Biopsy (fixed and frozen) and 
plasma biomarker sample 21
X
(Parts A, 
B only) 
X
(3 to 5 
days 
post 
C1D1)
Plasma PK and ADA
Refer to Table 18 (Parts A and A2) and Table 19 (Part B)


CX-2009
Clinical Module CTMX-M-2009-001
CytomX Therapeutics, Inc.
Confidential and Proprietary
Page 126 of 160
Amendment 7, 20 February 2020
Table 13.
Schedule of Procedures: Parts A, A2, and B
Page 3 of 4
Note: For Parts A, A2, and B, each cycle constitutes 21 days.
Study visits that cannot occur on the scheduled day due to unforeseen circumstances other than toxicity (eg, weather or holidays) should be completed as close to the 
scheduled date as possible. Laboratory assessments may be performed up to 2 days prior to the visit or as otherwise specified in the Schedule of Procedures. Visits conducted 
outside the windows are to be discussed with the Medical Monitor or designee in advance.
Medical history to include confirmation of previous cancer diagnosis, and record cancer treatment history, current symptoms at baseline, and current medications, as well as 
those taken within 30 days of first dose of study drug. An ophthalmology history is also required.
AEs will be assessed and reviewed prior to infusion and at any other visit that includes a physical examination. 
Concomitant medications will be assessed and reviewed prior to infusion and at any other visit that includes a physical examination. Changes in concomitant medications will 
be collected up to and including the EOT Visit. After EOT, only concomitant medications administered for irAEs occurring within 90 days after last dose will be recorded. 
Once a subject enters the Follow-Up Period, only new therapies for the treatment of their cancer should be recorded in the eCRFs.
CX-2009 will be administered by IV infusion every 21 days. There must be a MINIMUM of 21 days between infusions (a window of r2 days may occur). CX-2009 will be 
administered over 90 (r10) minutes with careful monitoring of IRRs. 
MRI (CT may also be acceptable) to be performed within 30 days prior to the first dose of CX-2009 as baseline and repeated for assessment of tumor response every 
8 (r1) weeks from the first dose of CX-2009 as per NCCN Guidelines until progression. Scans will be performed at a regular interval, regardless if CX-2009 dosing is delayed 
or modified. Scans will also be repeated at the EOT Visit (if the subject has not experienced progression). Tumor measurements will be recorded at baseline and repeated at 
regular intervals, as per the NCCN Guidelines for the specific tumor type. CR or PR must be confirmed at a second tumor assessment obtained at t4 weeks from the 
assessment at which CR or PR was first observed. Tumor response will be evaluated using RECIST (v1.1). Skin lesions (whether measurable or not) should be photographed 
along with a ruler at all time points for tumor assessments. MRI (CT scan may also be acceptable) will be performed every 12 weeks for subjects who have been on study 
drug >12 months. 
Bone scans will be performed as clinically indicated and at the discretion of the Investigator.
Twelve-lead ECGs should be obtained in triplicate (approximately 2 to 5 minutes apart), in digital format (when possible), and archived, while supine at Screening (within 
7 days prior to Cycle 1 Day 1), preinfusion and both 15 minutes and 1 hour post-EOI on Day 1 of Cycles 1 and 3 (only) and as clinically indicated, and at the EOT Visit. 
A full physical examination should be performed at Screening, prior to infusion of CX-2009, and at the EOT Visit. 
A targeted physical examination should be performed weekly during the DLT period, once each cycle, and as needed by subject symptoms or clinical observations, focused 
on key organ systems of interest (eg, CV, pulmonary, GI, skin, ophthalmic, endocrine, or any systems with previously noted abnormal findings).
A complete ophthalmologic examination (including visual acuity, indirect fundoscopy, slit lamp examination under dilatation, intraocular pressure measurement, corneal 
photography, and Schirmer’s test) will be performed in all subjects at baseline (within 5 days prior to the first dose of CX-2009); within 5 days prior to Cycle 2, Day 1; 
Cycle 3, Day 1; and at the EOT Visit by an ophthalmologist. Subjects who report treatment-emergent changes in vision or other ocular symptoms will undergo repeat 
examinations prior to infusion every other cycle and as clinically indicated.
The ocular symptom assessment will include assessment of blurred vision and ocular discomfort. The ocular symptom assessment will be performed at Screening, Day 1 of 
every cycle, and at the EOT Visit. If ocular toxicity occurs, see Section 5.5.3.2 and Section 5.5.4.1.
ECOG performance status should be assessed at Screening, Day 1 of every cycle, prior to each infusion, and at the EOT Visit.
Including CBC with differential, including platelet count and reticulocyte count, will be performed at Screening, preinfusion, weekly during treatment, and at the EOT Visit. 
Serum chemistry will include ALP, AST/SGOT and ALT/SGPT, total bilirubin, calcium, phosphorus, BUN, creatinine, total protein, albumin, glucose, potassium, sodium, 
chloride, magnesium, uric acid, LDH, and hemoglobin A1c, if clinically indicated. Blood glucose should be fasting at Screening and as indicated to evaluate possible 
hyperglycemia. Calculated creatinine clearance is required at Screening. Laboratory assessments drawn on the day of infusion should be drawn preinfusion.
Serum chemistry will only include electrolytes (potassium, sodium chloride, and magnesium) on Day 8 and Day 15 of every cycle.


CX-2009
Clinical Module CTMX-M-2009-001
CytomX Therapeutics, Inc.
Confidential and Proprietary
Page 127 of 160
Amendment 7, 20 February 2020
Table 13.
Schedule of Procedures: Parts A, A2, and B
Page 4 of 4
Coagulation will include PT/aPTT/INR at Screening, the EOT Visit, and as clinically indicated. If results are abnormal at Screening, then repeat prior to dosing or as clinically 
indicated.
Urinalysis (including assessment of protein, blood, leukocytes, glucose, ketones, bilirubin, urobilinogen, pH, and specific gravity) with microscopic examination at Screening 
and the EOT Visit. 
Serum pregnancy test (HCG) should be evaluated in all women of childbearing potential at Screening. If the Screening serum pregnancy test is obtained within 7 days of first 
infusion, the Day 1 pregnancy test may be omitted. Urine pregnancy test (with serum test as needed for confirmation) should be obtained prior to each cycle of therapy, at the 
EOT Visit, and at FU/EOS Visits through 50 days after the last dose of CX-2009.
Tumor marker assessments should be scheduled concurrently with CT for PSA and CA125 for appropriate tumor types; all others as clinically indicated.
Biopsies in subjects participating in the Part A dose escalation schema will be optional. For the subjects who consent to pretreatment and on-treatment tumor biopsies during 
dose escalation (Part A), tumor biopsies (fixed and frozen) will be collected during the Screening Period and 3 to 5 days after the first dose of CX-2009. Biopsy collection for 
the purpose of determining eligibility for Part A2 is not permitted. For Part A2, tumor biopsies (fixed and frozen) are required 3 to 5 days after the first dose of CX-2009, 
provided that the tumor is accessible and a biopsy is deemed safe by the treating physician. Paired plasma samples will be obtained at the time of the tumor biopsies. The 
technical details for the collection of specimens will be outlined in the Laboratory Manual. Biopsy collection for the purpose of determining eligibility for Part B is not 
permitted. For the dose expansion (Part B), consent to pretreatment and on-treatment tumor biopsies will be mandatory in at least 7 subjects for each tumor type. For these 
subjects, tumor biopsies (fixed and frozen) will be collected during the Screening Period (baseline) and 3 to 5 days after the first dose of CX-2009, provided that the tumor is 
accessible and a biopsy is deemed safe by the treating physician. 
Day 8 and Day 15 Visits are not needed for subjects who have been on study drug >4 months and have no ongoing tGrade 2 adverse events.
Day 4 Visit and assessments only for subjects who participate in the on-treatment tumor biopsies.
An EOT Visit will be conducted 30 days (r7 days) after the last infusion of CX-2009.
Follow-Up and EOS:
• If subject had documented progression, the subject may continue in the study if experiencing clinical benefit (as assessed by the Investigator) following consultation with the 
Medical Monitor or designee; otherwise, the subject will continue in survival Follow-Up Visits every 3 months (r14 days) after the EOT Visit for 1 year and then every
6 months (r14 days) (this may be by telephone), or until death. Subsequent cancer treatment will be collected.
• If subject has not had progression, imaging assessments will continue until progression is documented. Survival Follow-Up will be done every 3 months (r14 days) as 
described above.
• Women of childbearing potential will undergo pregnancy testing at FU/EOS Visits through 50 days after the last dose of CX-2009.
ADA = antidrug antibody; AE = adverse event; ALP = alkaline phosphatase; ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; BUN = blood urea nitrogen; CA125 = cancer antigen 125; CBC = complete blood count; CMV = cytomegalovirus; C1D1 = Cycle 1 Day 1; CR = complete 
response; CT = computed tomography; CV = cardiovascular; d = day; DLT = dose-limiting toxicity; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology group; 
eCRF = electronic case report form; EOI = end of infusion; EOS = end of study; EOT = end of treatment; FU = follow-up; GI = gastrointestinal; HCG = human chorionic 
gonadotropin; HIV = human immunodeficiency virus; INR = international normalized ratio; IRR = infusion-related reaction; IV = intravenous; LDH = lactate dehydrogenase; 
MRI = magnetic resonance imaging; NCCN = National Comprehensive Cancer Network; PK = pharmacokinetic; PR = partial response; PSA = prostate-specific antigen; 
PT = prothrombin time; RECIST = Response Evaluation Criteria in Solid Tumours; SGOT = serum glutamic oxaloacetic transaminase; SGPT = serum glutamic pyruvic 
transaminase.


CX-2009
Clinical Module CTMX-M-2009-001
CytomX Therapeutics, Inc.
Confidential and Proprietary
Page 128 of 160
Amendment 7, 20 February 2020
Table 14.
Schedule of Procedures: Parts C1 and C2
Page 1 of 4
Period/
Procedure
Screening
Treatment Period
FU/EOS 25
Cycle 1 DLT Assessment
Day 1 to Day 28
Cycle 2
Cycle 3 & On 22
EOT 24
Study/Visit Day 1
–30 to 0
1
4 23
(r1d)
8
(r2d)
15
(r2d)
22
(r2d)
1
(r2d)
8
(r2d)
15
(r2d)
22
(r2d)
1
(r2d)
8
(r2d)
15
(r2d)
22
(r2d)
(r7d)
Refer to 
footnote
Informed consent
X
Medical history 2
X
Demographics
X
AE assessment 3
X
X
X
X
X
X
X
X
X
Concomitant 
medications 4
X
X
X
X
X
X
X
X
X
X
HIV/CMV/
Hepatitis B, C
X
CX-2009
administration 5
X
X
X
X
X
X
CT/MRI (chest, 
abdomen, pelvis) 6
CT/MRI/Tumor assessment to be conducted every 8 (r1) weeks from the first dose of CX-2009 with assessment for response per RECIST Version 1.1
Bone scan 7
As clinically indicated
ECG 8
X
Day 1 of Cycles 1 and 2 and as clinically indicated for other visits
X
Full physical 
examination 9
X
X
Targeted physical 
examination 10
X
X
X
X
X
X
X
X


CX-2009
Clinical Module CTMX-M-2009-001
CytomX Therapeutics, Inc.
Confidential and Proprietary
Page 129 of 160
Amendment 7, 20 February 2020
Table 14.
Schedule of Procedures: Parts C1 and C2
See footnotes on the following page.
Page 2 of 4
Period/
Procedure
Screening
Treatment Period
FU/EOS 25
Cycle 1 DLT Assessment 
Day 1 to Day 28
Cycle 2
Cycle 3 & On 22
EOT 24
Study/Visit Day 1
-30 to 0
1
4 23
(r1d)
8
(r2d)
15
(r2d)
22
(r2d)
1
(r2d)
8
(r2d)
15
(r2d)
22
(r2d)
1
(r2d)
8
(r2d)
15
(r2d)
22
(r2d)
(r7d)
Refer to 
Footnote
Complete 
ophthalmology 
examination 11
X
All subjects within 5 days prior to Cycle 1, Day 1; Cycle 1 Day 15; Cycle 2, Day 1; and at the EOT Visit. Subjects who 
report treatment-emergent changes in vision or other ocular symptoms will undergo repeat examinations prior to infusion 
every other cycle and as clinically indicated.
Ocular symptom 
assessment 12
X
X
X
X
X
X
X
X
Vital signs
Refer to Table 17
ECOG 
performance 
status 13
X
X
X
X
X
X
X
X
Hematology 14
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum chemistry
15,16
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Coagulation 17
X
As clinically indicated
X
Urinalysis 18
X
X
Pregnancy test 19
X
X
X
X
X
X
X
X
X
Archival/
baseline tumor 
biopsy
X
Tumor markers 20
As clinically indicated
Biopsy (fixed and 
frozen) and 
plasma 
biomarker 
sample 21
X
X
(3 to 5 
days 
post 
C1D1)
Plasma PK and 
ADA
Refer to Table 20 (Part C1) and Table 21 (Part C2)


CX-2009
Clinical Module CTMX-M-2009-001
CytomX Therapeutics, Inc.
Confidential and Proprietary
Page 130 of 160
Amendment 7, 20 February 2020
Table 14.
Schedule of Procedures: Parts C1 and C2
Page 3 of 4
Note: For Parts C1 and C2, each cycle constitutes 28 days.
Study visits that cannot occur on the scheduled day due to unforeseen circumstances other than toxicity (eg, weather or holidays) should be completed as close to the 
scheduled date as possible. Laboratory assessments may be performed up to 2 days prior to the visit or as otherwise specified in the Schedule of Procedures. Visits conducted 
outside the windows are to be discussed with the Medical Monitor or designee in advance.
Medical history to include confirmation of previous cancer diagnosis, and record cancer treatment history, current symptoms at baseline, and current medications, as well as 
those taken within 30 days of first dose of study drug. An ophthalmology history is also required.
AEs will be assessed and reviewed prior to infusion and at any other visit that includes a physical examination. 
Concomitant medications will be assessed and reviewed prior to infusion and at any other visit that includes a physical examination. Changes in concomitant medications will 
be collected up to and including the EOT Visit. After EOT, only concomitant medications administered for irAEs occurring within 90 days after last dose will be recorded. 
Once a subject enters the Follow-Up Period, only new therapies for the treatment of their cancer should be recorded in the eCRFs.
CX-2009 will be administered by IV infusion every 14 days. There must be a MINIMUM of 14 days between infusions (a window of r2 days may occur). CX-2009 will be 
administered over 90 (r10) minutes with careful monitoring of IRRs. 
MRI (CT may also be acceptable) to be performed within 30 days prior to the first dose of CX-2009 as baseline and repeated for assessment of tumor response every 
8 (r1) weeks from the first dose of CX-2009 as per NCCN Guidelines until progression. Scans will be performed at a regular interval, regardless if CX-2009 dosing is delayed 
or modified. Scans will also be repeated at the EOT Visit (if the subject has not experienced progression). Tumor measurements will be recorded at baseline and repeated at 
regular intervals, as per the NCCN Guidelines for the specific tumor type. Complete response or PR must be confirmed at a second tumor assessment obtained at t4 weeks 
from the assessment at which CR or PR was first observed. Tumor response will be evaluated using RECIST (v1.1). Skin lesions (whether measurable or not) should be 
photographed along with a ruler at all time points for tumor assessments. MRI (CT scan may also be acceptable) will be performed every 12 weeks for subjects who have 
been on study drug >12 months.
Bone scans will be performed as clinically indicated and at the discretion of the Investigator.
Twelve-lead ECGs should be obtained in triplicate (approximately 2 to 5 minutes apart), in digital format (when possible), and archived, while supine at Screening (within 
7 days prior to Cycle 1 Day 1), preinfusion and both 15 minutes and 1 hour post-EOI on Day 1 of Cycles 1 and 2 (only) and as clinically indicated, and at the EOT Visit. 
A full physical examination should be performed at Screening, prior to infusion of CX-2009, and at the EOT Visit. 
A targeted physical examination should be performed weekly during the DLT period, prior to each infusion, and as needed by subject symptoms or clinical observations, 
focused on key organ systems of interest (eg, CV, pulmonary, GI, skin, ophthalmic, endocrine, or any systems with previously noted abnormal findings).
A complete ophthalmologic examination (including visual acuity, indirect fundoscopy, slit lamp examination under dilatation, intraocular pressure measurement, corneal 
photography, and Schirmer’s test) will be performed in all subjects at baseline (within 5 days prior to the first dose of CX-2009); within 5 days prior to Cycle 1, Day 1; 
Cycle 1 Day 15; Cycle 2, Day 1; and at the EOT Visit by an ophthalmologist. Subjects who report treatment-emergent changes in vision or other ocular symptoms will 
undergo repeat examinations prior to infusion every other cycle and as clinically indicated.
The ocular symptom assessment will include assessment of blurred vision and ocular discomfort. The ocular symptom assessment will be performed at Screening, prior to 
each infusion, and at the EOT Visit. If ocular toxicity occurs, see Section 5.5.3.2 and Section 5.5.4.1.
ECOG performance status should be assessed at Screening, Day 1 of every cycle, prior to each infusion, and at the EOT Visit.
Including CBC with differential, including platelet count and reticulocyte count, will be performed at Screening, preinfusion, weekly during treatment, and at the EOT Visit.
Serum chemistry will include ALP, AST/SGOT and ALT/SGPT, total bilirubin, calcium, phosphorus, BUN, creatinine, total protein, albumin, glucose, potassium, sodium, 
chloride, magnesium, uric acid, LDH, and hemoglobin A1c, if clinically indicated. Blood glucose should be fasting at Screening and as indicated to evaluate possible 
hyperglycemia. Calculated creatinine clearance is required at Screening. Laboratory assessments drawn on the day of infusion should be drawn preinfusion.
Serum chemistry will only include electrolytes (potassium, sodium chloride, and magnesium) on Days 8 and 22 of every cycle.


CX-2009
Clinical Module CTMX-M-2009-001
CytomX Therapeutics, Inc.
Confidential and Proprietary
Page 131 of 160
Amendment 7, 20 February 2020
Table 14.
Schedule of Procedures: Parts C1 and C2
Page 4 of 4
Coagulation will include PT/aPTT/INR at Screening, the EOT Visit, and as clinically indicated. If results are abnormal at Screening, then repeat prior to dosing or as clinically 
indicated.
Urinalysis (including assessment of protein, blood, leukocytes, glucose, ketones, bilirubin, urobilinogen, pH, and specific gravity) with microscopic examination at Screening 
and the EOT Visit. 
Serum pregnancy test (HCG) should be evaluated in all women of childbearing potential at Screening. If the Screening serum pregnancy test is obtained within 7 days of first 
infusion, the Day 1 pregnancy test may be omitted. Urine pregnancy test (with serum test as needed for confirmation) should be obtained prior to each CX-2009 infusion, at 
the EOT Visit, and at FU/EOS Visits through 50 days after the last dose of CX-2009.
Tumor marker assessments should be scheduled concurrently with CT for PSA and CA125 for appropriate tumor types; all others as clinically indicated.
For Part C1, pretreatment and on-treatment tumor biopsies will be optional. For the subjects who consent, tumor biopsies will be collected during the Screening Period 
(baseline) and 3 to 5 days after the first dose of CX-2009, provided that the tumor is accessible and a biopsy is deemed safe by the treating physician. Biopsy collection for the 
purpose of determining eligibility for Part C1 is not permitted. For Part C2, pretreatment and on-treatment tumor biopsies will be mandatory in at least 7 subjects for each 
tumor type. For these subjects, tumor biopsies (fixed and frozen) will be collected during the Screening Period (baseline) and 3 to 5 days after the first dose of CX-2009, 
provided that the tumor is accessible and a biopsy is deemed safe by the treating physician. Biopsy collection for the purpose of determining eligibility for Part C2 is not 
permitted.
Day 8 and Day 22 Visits are not needed for subjects who have been on study drug >4 months and have no ongoing tGrade 2 adverse events.
Day 4 Visit and assessments only for subjects who participate in the on-treatment tumor biopsies.
An EOT Visit will be conducted 30 days (r7 days) after the last infusion of CX-2009.
Follow-Up and EOS:
• If subject had documented progression, the subject may continue in the study if experiencing clinical benefit (as assessed by the Investigator) following consultation with the 
Medical Monitor or designee; otherwise, the subject will continue in survival Follow-Up Visits every 3 months (r14 days) after the EOT Visit for 1 year and then every 
6 months (r14 days) (this may be by telephone), or until death. Subsequent cancer treatment will be collected.
• If subject has not had progression, imaging assessments will continue until progression is documented. Survival Follow-Up will be done every 3 months (r14 days) as 
described above.
• Women of childbearing potential will undergo pregnancy testing at FU/EOS Visits through 50 days after the last dose of CX-2009.
ADA = antidrug antibody; AE = adverse event; ALP = alkaline phosphatase; ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; BUN = blood urea nitrogen; CA125 = cancer antigen 125; CBC = complete blood count; CMV = cytomegalovirus; C1D1 = Cycle 1 Day 1; CR = complete 
response; CT = computed tomography; CV = cardiovascular; d = day; DLT = dose-limiting toxicity; ECG = electrocardiogram; ECOG = Eastern cooperative Oncology group; 
eCRF = electronic case report form; EOI = End of Infusion; EOS = End of Study; EOT = End of Treatment; FU = Follow-Up; GI = gastrointestinal; HCG = human chorionic 
gonadotropin; HIV = human immunodeficiency virus; INR = international normalized ratio; IRR = infusion-related reaction; IV = intravenous; LDH = lactate dehydrogenase; 
MRI = magnetic resonance imaging; NCCN = National Comprehensive Cancer Network; PK = pharmacokinetic; PR = partial response; PSA = prostate-specific antigen; 
PT = prothrombin time; RECIST = Response Evaluation Criteria in Solid Tumours; SGOT = serum glutamic oxaloacetic transaminase; SGPT = serum glutamic pyruvic 
transaminase.


CX-2009
Clinical Module CTMX-M-2009-001
CytomX Therapeutics, Inc.
Confidential and Proprietary
Page 132 of 160
Amendment 7, 20 February 2020
Table 15.
Schedule of Procedures: Parts D1 and D2
Page 1 of 4
Period/Procedure
Screening
Treatment Period
FU/EOS 26
Cycle 1 DLT Assessment
Day 1 to Day 28
Cycle 2
Cycle 3 & On 23
EOT 25
Study/Visit Day 1
–30 to 0
1
4
(r1d)
8
(r2d)
15
(r2d)
22
(r2d)
1
(r2d)
8
(r2d)
15
(r2d)
22
(r2d)
1
(r2d)
8
(r2d)
15
(r2d)
22
(r2d)
(r7d)
Refer to 
footnote
Informed consent
X
Medical history 2
X
Demographics
X
AE assessment 3
X
X
X
X
X
X
X
X
X
Concomitant 
medications 4
X
X
X
X
X
X
X
X
X
X
HIV/CMV/
Hepatitis B, C
X
CX-2009
administration 5
X
X
X
X
X
X
CX-072
administration 6
X
X
X
X
X
X
CT/MRI (chest, 
abdomen, pelvis)7
CT/MRI/Tumor assessment to be conducted every 8 (r1) weeks from the first dose of study treatment with assessment for response per RECIST 
Version 1.1 and per irRECIST (Parts D1 and D2)
Bone scan 8
As clinically indicated
ECG 9
X
Day 1 of Cycles 1 and 2 and as clinically indicated for other visits
X
Full physical 
examination 10
X
X
Targeted physical 
examination 11
X
X
X
X
X
X
X
X
Complete 
ophthalmology 
examination 12
X
All subjects within 5 days prior to Cycle 1, Day 1; Cycle 1 Day 15; Cycle 2, Day 1; and at the EOT Visit. Subjects who 
report treatment-emergent changes in vision or other ocular symptoms will undergo repeat examinations prior to infusion 
every other cycle and as clinically indicated.


CX-2009
Clinical Module CTMX-M-2009-001
CytomX Therapeutics, Inc.
Confidential and Proprietary
Page 133 of 160
Amendment 7, 20 February 2020
Table 15.
Schedule of Procedures: Parts D1 and D2
See footnotes on the following page.
Page 2 of 4
Period/Procedure
Screening
Treatment Period
FU/EOS 26
Cycle 1 DLT Assessment 
Day 1 to Day 28
Cycle 2
Cycle 3 & On 23
EOT 25
Study/Visit Day 1
-30 to 0
1
4
(r1d)
8
(r2d)
15
(r2d)
22
(r2d)
1
(r2d)
8
(r2d)
15
(r2d)
22
(r2d)
1
(r2d)
8
(r2d)
15
(r2d)
22
(r2d)
(r7d)
Refer to 
footnote
Ocular symptom 
assessment 13
X
X
X
X
X
X
X
X
Vital signs
Refer to Table 17
ECOG performance 
status 14
X
X
X
X
X
X
X
X
Hematology 15
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum 
chemistry 16,17
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Coagulation 18
X
As clinically indicated
X
Urinalysis 19
X
X
Pregnancy test 20
X
X
X
X
X
X
X
X
X
Archival/
baseline tumor biopsy
X
Tumor markers 21
As clinically indicated
Biopsy (fixed and 
frozen) and plasma 
biomarker sample 22
X
(3 to 5 
days after 
C2D1)
Plasma PK and ADA 
sample
Refer to Table 22 (Part D1) and 
Table 23 (Part D2)


CX-2009
Clinical Module CTMX-M-2009-001
CytomX Therapeutics, Inc.
Confidential and Proprietary
Page 134 of 160
Amendment 7, 20 February 2020
Table 15.
Schedule of Procedures: Parts D1 and D2
Page 3 of 4
Note: For Parts D1 and D2, each cycle constitutes 28 days.
Study visits that cannot occur on the scheduled day due to unforeseen circumstances other than toxicity (eg, weather or holidays) should be completed as close to the 
scheduled date as possible. Laboratory assessments may be performed up to 2 days prior to the visit or as otherwise specified in the Schedule of Procedures. Visits conducted 
outside the windows are to be discussed with the Medical Monitor or designee in advance.
Medical history to include confirmation of previous cancer diagnosis, and record cancer treatment history, current symptoms at baseline, and current medications, as well as 
those taken within 30 days of first dose of study drug. An ophthalmology history is also required.
AEs will be assessed and reviewed prior to infusion and at any other visit that includes a physical examination. 
Concomitant medications will be assessed and reviewed prior to infusion and at any other visit that includes a physical examination. Changes in concomitant medications will 
be collected up to and including the EOT Visit. After EOT, only concomitant medications administered for irAEs occurring within 90 days after last dose will be recorded. 
Once a subject enters the Follow-Up Period, only new therapies for the treatment of their cancer should be recorded in the eCRFs.
CX-2009 will be administered by IV infusion every 14 days. There must be a MINIMUM of 14 days between infusions (a window of r2 days may occur). CX-2009 will be 
administered over 90 (r10) minutes with careful monitoring of IRRs. When CX-2009 and CX-072 are administered on the same day, CX-072 is to be administered first, 
followed by a saline flush, followed by the CX-2009 infusion. CX-2009 is to be infused no sooner than 30 minutes after completion of the CX-072 infusion. 
800 mg CX-072 is to be administered over 60 (r10) minutes. When CX-2009 and CX-072 are administered on the same day, CX-072 is to be administered first, followed by a 
saline flush, followed by the CX-2009 infusion. CX-2009 is to be infused no sooner than 30 minutes after completion of the CX-072 infusion. 
MRI (CT may also be acceptable) to be performed within 30 days prior to the first dose of study treatment as baseline and repeated for assessment of tumor response every 
8 (r1) weeks from the first dose of study treatment as per NCCN Guidelines until progression. Scans will be performed at a regular interval, regardless if study treatment is 
delayed or modified. Scans will also be repeated at the EOT Visit (if the subject has not experienced progression). Tumor measurements will be recorded at baseline and 
repeated at regular intervals, as per the NCCN Guidelines for the specific tumor type. CR or PR must be confirmed at a second tumor assessment obtained at t4 weeks from 
the assessment at which CR or PR was first observed. Tumor response will be evaluated using RECIST (v1.1) and irRECIST (Parts D1 and D2). Skin lesions (whether 
measurable or not) should be photographed along with a ruler at all time points for tumor assessments. MRI (CT scan may also be acceptable) will be performed every 
12 weeks for subjects who have been on study drug >12 months.
Bone scans will be performed as clinically indicated and at the discretion of the Investigator.
Twelve-lead ECGs should be obtained in triplicate (approximately 2 to 5 minutes apart), in digital format (when possible), and archived, while supine at Screening (within 
7 days prior to Cycle 1 Day 1), preinfusion and both 15 minutes and 1 hour post-EOI on Day 1 of Cycles 1 and 2 (only) and as clinically indicated, and at the EOT Visit. 
A full physical examination should be performed at Screening, prior to infusion of study treatment, and at the EOT Visit. 
A targeted physical examination should be performed weekly during the DLT period, prior to each infusion, and as needed by subject symptoms or clinical observations, 
focused on key organ systems of interest (eg, CV, pulmonary, GI, skin, ophthalmic, endocrine, or any systems with previously noted abnormal findings).
A complete ophthalmologic examination (including visual acuity, indirect fundoscopy, slit lamp examination under dilatation, intraocular pressure measurement, corneal 
photography, and Schirmer’s test) will be performed in all subjects at baseline (within 5 days prior to the first dose of CX-2009); within 5 days prior to Cycle 1, Day 1; 
Cycle 1 Day 15; Cycle 2, Day 1; and at the EOT Visit by an ophthalmologist. Subjects who report treatment-emergent changes in vision or other ocular symptoms will 
undergo repeat examinations prior to infusion every other cycle and as clinically indicated.
The ocular symptom assessment will include assessment of blurred vision and ocular discomfort. The ocular symptom assessment will be performed at Screening, prior to 
each infusion, and at the EOT Visit. If ocular toxicity occurs, see Section 5.5.3.2 and Section 5.5.4.1.
ECOG performance status should be assessed at Screening, Day 1 of every cycle, prior to each infusion, and at the EOT Visit.
Including CBC with differential, including platelet count and reticulocyte count, will be performed at Screening, preinfusion, weekly during treatment, and at the EOT Visit. 


CX-2009
Clinical Module CTMX-M-2009-001
CytomX Therapeutics, Inc.
Confidential and Proprietary
Page 135 of 160
Amendment 7, 20 February 2020
Table 15.
Schedule of Procedures: Parts D1 and D2
Page 4 of 4
Serum chemistry will include ALP, AST/SGOT and ALT/SGPT, total bilirubin, calcium, phosphorus, BUN, creatinine, total protein, albumin, glucose, potassium, sodium, 
chloride, magnesium, uric acid, LDH, and hemoglobin A1c, if clinically indicated. Blood glucose should be fasting at Screening and as indicated to evaluate possible 
hyperglycemia. Calculated creatinine clearance is required at Screening. Laboratory assessments drawn on the day of infusion should be drawn preinfusion.
Serum chemistry will only include electrolytes (potassium, sodium chloride, and magnesium) on Days 8 and 22 of every cycle.
Coagulation will include PT/aPTT/INR at Screening, the EOT Visit, and as clinically indicated. If results are abnormal at Screening, then repeat prior to dosing or as clinically 
indicated.
Urinalysis (including assessment of protein, blood, leukocytes, glucose, ketones, bilirubin, urobilinogen, pH, and specific gravity) with microscopic examination at Screening 
and the EOT Visit. 
Serum pregnancy test (HCG) should be evaluated in all women of childbearing potential at Screening. If the Screening serum pregnancy test is obtained within 7 days of first 
infusion, the Day 1 pregnancy test may be omitted. Urine pregnancy test (with serum test as needed for confirmation) should be obtained prior to each study treatment 
infusion, at the EOT Visit, and at FU/EOS Visits through 50 days after the last dose of CX-2009 or 6 months after the last dose of CX-072, whichever is later.
Tumor marker assessments should be scheduled concurrently with CT for PSA and CA125 for appropriate tumor types; all others as clinically indicated.
For both Parts D1 and D2, on-treatment tumor biopsies will be optional. For the subjects who consent, tumor biopsies will be collected 3 to 5 days after the third dose of study 
treatment, provided that the tumor is accessible and a biopsy is deemed safe by the treating physician. Biopsy collection for the purpose of determining eligibility for Part D1 
or D2 is not permitted.
Day 8 and Day 22 Visits are not needed for subjects who have been on study drug >4 months and have no ongoing tGrade 2 adverse events.
An EOT Visit will be conducted 30 days (r7 days) after the last infusion of study treatment.
Follow-Up and EOS:
• If subject had documented progression, the subject may continue in the study if experiencing clinical benefit (as assessed by the Investigator) following consultation with the 
Medical Monitor or designee; otherwise, the subject will continue in survival Follow-Up Visits every 3 months (r14 days) after the EOT Visit for 1 year and then every 
6 months (r14 days) (this may be by telephone), or until death. Subsequent cancer treatment will be collected.
• If subject has not had progression, imaging assessments will continue until progression is documented. Survival Follow-Up will be done every 3 months (r14 days) as 
described above.
• Women of childbearing potential will undergo pregnancy testing at FU/EOS Visits through 50 days after the last dose of CX-2009 or 6 months after the last dose of CX-072, 
whichever is later.
ADA = antidrug antibody; AE = adverse event; ALP = alkaline phosphatase; ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; BUN = blood urea nitrogen; CA125 = cancer antigen 125; CBC = complete blood count; CMV = cytomegalovirus; CR = complete response; CT = computed 
tomography; CV = cardiovascular; d = day; DLT = dose-limiting toxicity; ECG = electrocardiogram; ECOG = Eastern cooperative Oncology group; eCRF = electronic case report 
form; EOI = End of Infusion; EOS = End of Study; EOT = End of Treatment; FU = Follow-Up; GI = gastrointestinal; HCG = human chorionic gonadotropin; HIV = human 
immunodeficiency virus; INR = international normalized ratio; IRR = infusion-related reaction; irRECIST = Immune-related Response Criteria in Solid Tumours; 
IV = intravenous; LDH = lactate dehydrogenase; MRI = magnetic resonance imaging; NCCN = National Comprehensive Cancer Network; PK = pharmacokinetic; PR = partial 
response; PSA = prostate-specific antigen; PT = prothrombin time; RECIST = Response Evaluation Criteria in Solid Tumours; SGOT = serum glutamic oxaloacetic transaminase; 
SGPT = serum glutamic pyruvic transaminase.


CX-2009
Clinical Module CTMX-M-2009-001
CytomX Therapeutics, Inc.
Confidential and Proprietary
Page 136 of 160
Amendment 7, 20 February 2020
Table 16.
Schedule of Procedures: Parts E1 and E2
Page 1 of 4
Period/
Procedure
Screening
Treatment Period
FU/EOS 25
Cycle 1 DLT Assessment
Day 1 to Day 21
Cycle 2
Cycle 3 & On 23
EOT 24
Study/Visit Day 1
–30 to 0
1
4 22
(r1d)
8
(r2d)
15
(r2d)
1
(r2d)
8
(r2d)
15
(r2d)
1
(r2d)
8
(r2d)
15
(r2d)
(r7d)
Refer to 
Footnote
Informed consent
X
Medical history 2
X
Demographics
X
AE assessment 3
X
X
X
X
X
X
Concomitant medications 4
X
X
X
X
X
X
X
HIV/CMV/
Hepatitis B, C
X
CX-2009 administration 5
X
X
X
CX-072 administration 6
X
X
X
CT/MRI (chest, abdomen, 
pelvis) 7
CT/MRI/Tumor assessment to be conducted every 8 (r1) weeks from the first dose of CX-2009 with assessment for response per
RECIST Version 1.1 and per irRECIST (Parts E1 and E2)
Bone scan 8
As clinically indicated
ECG 9
X
Day 1 of Cycles 1 and 3 and as clinically indicated for other visits
X
Full physical 
examination 10
X
X
Targeted physical 
examination 11
X
X
X
X
X
See footnotes on the following page.


CX-2009
Clinical Module CTMX-M-2009-001
CytomX Therapeutics, Inc.
Confidential and Proprietary
Page 137 of 160
Amendment 7, 20 February 2020
Table 16.  
Schedule of Procedures: Parts E1 and E2
Page 2 of 4
Period/
Procedure
Screening
Treatment Period
FU/EOS 25
Cycle 1 DLT Assessment
Day 1 to Day 21
Cycle 2
Cycle 3 & On 23
EOT 24
Study/Visit Day 1
–30 to 0
1
4
(r1d)
8
(r2d)
15
(r2d)
1
(r2d)
8
(r2d)
15
(r2d)
1
(r2d)
8
(r2d)
15
(r2d)
(r7d)
Refer to 
footnote
Complete ophthalmology 
examination 12
X
All subjects within 5 days prior to Cycle 1, Day 1; Cycle 2, Day 1; Cycle 3, Day 1; and at the EOT Visit. Subjects 
who report treatment-emergent changes in vision or other ocular symptoms will undergo repeat examinations 
prior to infusion every other cycle and as clinically indicated.
Ocular symptom assessment 13
X
X
X
X
X
Vital signs
Refer to Table 17
ECOG performance status 14
X
X
X
X
X
Hematology 15
X
X
X
X
X
X
X
X
X
X
X
Serum chemistry 16,17
X
X
X
X
X
X
X
X
X
X
X
Coagulation 18
X
As clinically indicated
X
Urinalysis 19
X
X
Pregnancy test 20
X
X
X
X
X
X
Archival/baseline tumor biopsy
X
Tumor markers 21
As clinically indicated
Biopsy (fixed and frozen) and 
plasma biomarker sample 22
X
(3 to 5 
days 
after 
C2D1)
Plasma PK and ADA
Refer to Table 24 (Part E1) and Table 25 (Part E2)


CX-2009
Clinical Module CTMX-M-2009-001
CytomX Therapeutics, Inc.
Confidential and Proprietary
Page 138 of 160
Amendment 7, 20 February 2020
Table 16.
Schedule of Procedures: Parts E1 and E2
Page 3 of 4
Note: For Parts E1 and E2, each cycle constitutes 21 days.
Study visits that cannot occur on the scheduled day due to unforeseen circumstances other than toxicity (eg, weather or holidays) should be completed as close to the 
scheduled date as possible. Laboratory assessments may be performed up to 2 days prior to the visit or as otherwise specified in the Schedule of Procedures. Visits conducted 
outside the windows are to be discussed with the Medical Monitor or designee in advance.
Medical history to include confirmation of previous cancer diagnosis, and record cancer treatment history, current symptoms at baseline, and current medications, as well as 
those taken within 30 days of first dose of study drug. An ophthalmology history is also required.
AEs will be assessed and reviewed prior to infusion and at any other visit that includes a physical examination. 
Concomitant medications will be assessed and reviewed prior to infusion and at any other visit that includes a physical examination. Changes in concomitant medications will 
be collected up to and including the EOT Visit. After EOT, only concomitant medications administered for irAEs occurring within 90 days after last dose will be recorded. 
Once a subject enters the Follow-Up Period, only new therapies for the treatment of their cancer should be recorded in the eCRFs.
CX-2009 will be administered by IV infusion every 21 days. There must be a MINIMUM of 21 days between infusions (a window of r2 days may occur). CX-2009 will be 
administered over 90 (r10) minutes with careful monitoring of IRRs. When CX-2009 and CX-072 are administered on the same day, CX-072 is to be administered first, 
followed by a saline flush, followed by the CX-2009 infusion. CX-2009 is to be infused no sooner than 30 minutes after completion of the CX-072 infusion. 
1200 mg CX-072 is to be administered over 60 (r10) minutes. When CX-2009 and CX-072 are administered on the same day, CX-072 is to be administered first, followed by 
a saline flush, followed by the CX-2009 infusion. CX-2009 is to be infused no sooner than 30 minutes after completion of the CX-072 infusion. 
MRI (CT may also be acceptable) to be performed within 30 days prior to the first dose of CX-2009 as baseline and repeated for assessment of tumor response every 
8 (r1) weeks from the first dose of study treatment as per NCCN Guidelines until progression. Scans will be performed at a regular interval, regardless if study treatment is 
delayed or modified. Scans will also be repeated at the EOT Visit (if the subject has not experienced progression). Tumor measurements will be recorded at baseline and 
repeated at regular intervals, as per the NCCN Guidelines for the specific tumor type. CR or PR must be confirmed at a second tumor assessment obtained at t4 weeks from 
the assessment at which CR or PR was first observed. Tumor response will be evaluated using RECIST (v1.1) and irRECIST (Parts E1 and E2). Skin lesions (whether 
measurable or not) should be photographed along with a ruler at all time points for tumor assessments. MRI (CT scan may also be acceptable) will be performed every 
12 weeks for subjects who have been on study drug >12 months.
Bone scans will be performed as clinically indicated and at the discretion of the Investigator.
Twelve-lead ECGs should be obtained in triplicate (approximately 2 to 5 minutes apart), in digital format (when possible), and archived, while supine at Screening (within 
7 days prior to Cycle 1 Day 1), preinfusion and both 15 minutes and 1 hour post-EOI on Day 1 of Cycles 1 and 3 (only) and as clinically indicated, and at the EOT Visit. 
A full physical examination should be performed at Screening, prior to infusion of study treatment, and at the EOT Visit. 
A targeted physical examination should be performed weekly during the DLT period, prior to infusion of study treatment, and as needed by subject symptoms or clinical 
observations, focused on key organ systems of interest (eg, CV, pulmonary, GI, skin, ophthalmic, endocrine, or any systems with previously noted abnormal findings).
A complete ophthalmologic examination (including visual acuity, indirect fundoscopy, slit lamp examination under dilatation, intraocular pressure measurement, corneal 
photography, and Schirmer’s test) will be performed in all subjects at baseline (within 5 days prior to the first dose of CX-2009); within 5 days prior to Cycle 2, Day 1; 
Cycle 3, Day 1; and at the EOT Visit by an ophthalmologist. Subjects who report treatment-emergent changes in vision or other ocular symptoms will undergo repeat 
examinations prior to infusion every other cycle and as clinically indicated.
The ocular symptom assessment will include assessment of blurred vision and ocular discomfort. The ocular symptom assessment will be performed at Screening, prior to 
each infusion, and at the EOT Visit. If ocular toxicity occurs, see Section 5.5.3.2 and Section 5.5.4.1.
ECOG performance status should be assessed at Screening, Day 1 of every cycle, prior to each infusion, and at the EOT Visit.
Including CBC with differential, including platelet count and reticulocyte count, will be performed at Screening, preinfusion, weekly during treatment, and at the EOT Visit. 


CX-2009
Clinical Module CTMX-M-2009-001
CytomX Therapeutics, Inc.
Confidential and Proprietary
Page 139 of 160
Amendment 7, 20 February 2020
Table 16.
Schedule of Procedures: Parts E1 and E2
Page 4 of 4
Serum chemistry will include ALP, AST/SGOT and ALT/SGPT, total bilirubin, calcium, phosphorus, BUN, creatinine, total protein, albumin, glucose, potassium, sodium, 
chloride, magnesium, uric acid, LDH, and hemoglobin A1c, if clinically indicated. Blood glucose should be fasting at Screening and as indicated to evaluate possible 
hyperglycemia. Calculated creatinine clearance is required at Screening. Laboratory assessments drawn on the day of infusion should be drawn preinfusion.
Serum chemistry will only include electrolytes (potassium, sodium chloride, and magnesium) on Day 8 and Day 15 of every cycle.
Coagulation will include PT/aPTT/INR at Screening, the EOT Visit, and as clinically indicated. If results are abnormal at Screening, then repeat prior to dosing or as clinically 
indicated.
Urinalysis (including assessment of protein, blood, leukocytes, glucose, ketones, bilirubin, urobilinogen, pH, and specific gravity) with microscopic examination at Screening 
and the EOT Visit. 
Serum pregnancy test (HCG) should be evaluated in all women of childbearing potential at Screening. If the Screening serum pregnancy test is obtained within 7 days of first 
infusion, the Day 1 pregnancy test may be omitted. Urine pregnancy test (with serum test as needed for confirmation) should be obtained prior to each study treatment, at the 
EOT Visit, and at FU/EOS Visits through 50 days after the last dose of CX-2009 or 6 months after the last dose of CX-072, whichever is later.
Tumor marker assessments should be scheduled concurrently with CT for PSA and CA125 for appropriate tumor types; all others as clinically indicated.
For both Parts E1 and E2, on-treatment tumor biopsies will be optional. For the subjects who consent, tumor biopsies will be collected 3 to 5 days after the third dose of study 
treatment, provided that the tumor is accessible and a biopsy is deemed safe by the treating physician. Biopsy collection for the purpose of determining eligibility for Part E1 
or E2 is not permitted.
Day 8 and Day 15 Visits are not needed for subjects who have been on study drug >4 months and have no ongoing tGrade 2 adverse events.
An EOT Visit will be conducted 30 days (r7 days) after the last infusion of study treatment.
Follow-Up and EOS:
• If subject had documented progression, the subject may continue in the study if experiencing clinical benefit (as assessed by the Investigator) following consultation with the 
Medical Monitor or designee; otherwise, the subject will continue in survival Follow-Up Visits every 3 months (r14 days) after the EOT Visit for 1 year and then every 
6 months (r14 days) (this may be by telephone), or until death. Subsequent cancer treatment will be collected.
• If subject has not had progression, imaging assessments will continue until progression is documented. Survival Follow-Up will be done every 3 months (r14 days) as 
described above.
• Women of childbearing potential will undergo pregnancy testing at FU/EOS Visits through 50 days after the last dose of CX-2009 or 6 months after the last dose of CX-072, 
whichever is later.
ADA = antidrug antibody; AE = adverse event; ALP = alkaline phosphatase; ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; BUN = blood urea nitrogen; CA125 = cancer antigen 125; CBC = complete blood count; CMV = cytomegalovirus; CR = complete response; CT = computed 
tomography; CV = cardiovascular; d = day; DLT = dose-limiting toxicity; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology group; eCRF = electronic case report 
form; EOI = end of infusion; EOS = end of study; EOT = end of treatment; FU = follow-up; GI = gastrointestinal; HCG = human chorionic gonadotropin; HIV = human 
immunodeficiency virus; INR = international normalized ratio; IRR = infusion-related reaction; irRECIST = Immune-related Response Criteria in Solid Tumours; 
IV = intravenous; LDH = lactate dehydrogenase; MRI = magnetic resonance imaging; NCCN = National Comprehensive Cancer Network; PK = pharmacokinetic; PR = partial 
response; PSA = prostate-specific antigen; PT = prothrombin time; RECIST = Response Evaluation Criteria in Solid Tumours; SGOT = serum glutamic oxaloacetic transaminase; 
SGPT = serum glutamic pyruvic transaminase.


CX-2009
Clinical Module CTMX-M-2009-001
CytomX Therapeutics, Inc.
Confidential and Proprietary
Page 140 of 160
Amendment 7, 20 February 2020
Table 17.
Schedule of Vital Signs Measurements: All Parts
Period/Procedure
Screening a
Cycles 1 to 6
Cycles 7 & On
EOT b
Time of Measurement
Preinfusion
EOI
Preinfusion
EOI
Height
X
Weight
X
X
X
X
Heart rate
X
X
X
X
X
X
Blood pressure
X
X
X
X
X
X
Temperature
X
X
X
X
X
X
Respiratory rate
X
X
X
X
X
X
Pulse oximetry
X
X
X
X
X
X
During the first 6 doses of study drug, vital signs should be measured within 60 minutes prior to infusion, every 15 (r5) minutes during infusion, at the EOI (r5 minutes), and 
approximately hourly for 4 hours after the completion of the infusion. On all other infusion days, vital signs should be measured within 60 minutes prior to infusion, at the EOI
(r5 minutes), and 60 (r5) minutes after completion of the infusion (unless clinical signs require more frequent monitoring). Height should be measured at the Screening Visit 
only. Weight should be measured at Screening and Day 1 of each cycle. During an IRR, vital signs should be recorded every 2 to 5 minutes until stable.
a Screening Visit = Study Days -30 to -1.
b EOT Visit to be conducted 30 (r7) days after the last infusion of study treatment.
EOI = end of infusion; EOT = end of treatment; IRR = infusion-related reaction.


CX-2009
Clinical Module CTMX-M-2009-001
CytomX Therapeutics, Inc.
Confidential and Proprietary
Page 141 of 160
Amendment 7, 20 February 2020
Table 18.
Schedule of PK and ADA Assessments: Parts A and A2 
Period/Procedure
Cycle 1
Cycles 2, 4, 
6, 8, & Every 
8 Cycles 
Thereafter
Cycle 3
EOT
Follow-up
Visit 1
Cycle Day
1
2
3
4
8
15
1
1
8
15
DOV
DOV
Time of Draw
Preinfusion
Post-
EOI
DOV
DOV
DOV
DOV
DOV
Preinfusion
Preinfusion
Post-
EOI
DOV
DOV
CX-2009 Plasma PK a
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CX-2009 Serum ADA b
X
X
X
X
X
Notes: Parts A and A2 cycle length is 21 days. Serial blood samples will be collected to characterize the PK of the Probody therapeutic in all subjects. Blood samples will be 
collected to assess the extent of ADA response to the Probody therapeutic. Actual times of CX-2009 dosing and PK/ADA collection must be recorded.
a PK samples will be drawn at the following times: 
• Cycle 1 Day 1: preinfusion, 15 (r10) minutes post-EOI, and 1 hour (r10 minutes) post-EOI
• Cycle 1 Day 2 (r6 hours)
• Cycle 1 Day 3 (r12 hours)
• Cycle 1 Day 4 (r12 hours) – Day 4 PK samples only for subjects who participate in the on-treatment tumor biopsies
• Cycle 1 Day 8 (r1 day)
• Cycle 1 Day 15 (r1 day)
• Cycles 2, 4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion (up to 2 days before infusion)
• Cycle 3 Day 1: preinfusion (up to 2 days before infusion), 15 (r10) minutes post-EOI, and 1 hour (r10 minutes) post-EOI
• Cycle 3 Day 8 (r2 days)
• Cycle 3 Day 15 (r2 days)
• EOT (DOV)
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009
b ADA samples will be drawn at the following times (to coincide with PK collections):
• Cycles 1, 2, 3, 4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion (up to 2 days before infusion)
• EOT (DOV)
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009
ADA = antidrug antibody; DOV = day of visit; EOI = end of infusion; EOT = end of treatment; PK = pharmacokinetic.


CX-2009
Clinical Module CTMX-M-2009-001
CytomX Therapeutics, Inc.
Confidential and Proprietary
Page 142 of 160
Amendment 7, 20 February 2020
Table 19.
Schedule of PK and ADA Assessments: Part B
Period/Procedure
Cycle 1
Cycles 2, 4, 6, 8, & 
Every 8 Cycles 
Thereafter
Cycle 3
EOT
Follow- up
Visit 1
Cycle Day
1
1
1
DOV
DOV
Time of Draw
Preinfusion
Post-EOI
Preinfusion
Preinfusion
Post-EOI
CX-2009 Plasma PK a
X
X
X
X
X
X
X
CX-2009 Serum ADA b
X
X
X
X
X
Notes: Part B cycle lengths are 21 days. Sparse blood samples will be collected to characterize the PK of the Probody therapeutic in all subjects. Blood samples will be 
collected to assess the extent of ADA response to the Probody therapeutic. Actual times of CX-2009 dosing and PK/ADA collection must be recorded.
a PK samples will be drawn at the following times: 
• Cycle 1 Day 1: preinfusion, 15 (r10) minutes post-EOI
• Cycles 2, 4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion (up to 2 days before infusion)
• Cycle 3 Day 1: preinfusion (up to 2 days before infusion), 15 (r10) minutes post-EOI
• EOT (DOV)
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009
b ADA samples will be drawn at the following times (to coincide with PK collections):
• Cycles 1, 2, 3, 4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion (up to 2 days before infusion)
• EOT (DOV)
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009
ADA = antidrug antibody; DOV = day of visit; EOI = end of infusion; EOT = end of treatment; PK = pharmacokinetic.


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Table 20.
Schedule of PK and ADA Assessments: Part C1
Period/
Procedure
Cycle 1
Cycle 2
Cycles 3, 4, 6, 8 
& Every 8 Cycles 
Thereafter
EOT
Follow- up
Visit 1
Cycle Day
1
2
3
4
8
15
1
8
15
1
DOV
DOV
Time of Draw
Preinfusion
Post-
EOI
DOV DOV DOV DOV Preinfusion Preinfusion
Post-
EOI
DOV Preinfusion
Preinfusion
CX-2009 Plasma PK a
X
X
X
X
X
X
X
X
X
X
X
X
X
X
CX-2009 Serum ADA b
X
X
X
X
X
X
X
Notes: Part C1 cycle length is 28 days. Serial blood samples will be collected to characterize the PK of the Probody therapeutic in all subjects. Blood samples will be collected to 
assess the extent of ADA response to the Probody therapeutic. Actual times of CX-2009 dosing and PK/ADA collection must be recorded.
a PK samples will be drawn at the following times: 
• Cycle 1 Day 1: preinfusion, 15 (r10) minutes post-EOI, and 1 hour (r10 minutes) post-EOI
• Cycle 1 Day 2 (r6 hours)
• Cycle 1 Day 3 (r12 hours)
• Cycle 1 Day 4 (r12 hours) - Day 4 PK samples will be only drawn for subjects who participate in the on-treatment tumor biopsies.
• Cycle 1 Day 8 (r1 day)
• Cycle 1 Day 15: preinfusion (up to 1 day before infusion)
• Cycle 2 Day 1: preinfusion, 15 (r10) minutes post-EOI, and 1 hour (r10 minutes) post-EOI
• Cycle 2 Day 8 (r2 days)
• Cycle 2 Day 15: preinfusion
• Cycles 3,4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion
• EOT
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009
b ADA samples will be drawn at the following times (to coincide with PK collections):
• Cycle 1 Day 1: preinfusion
• Cycle 1 Day 15: preinfusion
• Cycle 2 Day 1: preinfusion
• Cycle 2 Day 15: preinfusion
• Cycles 3, 4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion (up to 2 days before infusion)
• EOT (DOV)
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009
ADA = antidrug antibody; D = day; DOV = day of visit; EOI = end of infusion; EOT = end of treatment; PK = pharmacokinetic.


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Table 21.
Schedule of PK and ADA Assessments: Parts C2
Period/Procedure
Cycle 1
Cycle 2
Cycles 3, 4, 
6, 8 & Every 
8 Cycles 
Thereafter
EOT
Follow- up
Visit 1
Cycle Day
1
15
1
15
1
Time of Draw
Preinfusion
Post-EOI
Preinfusion
Preinfusion
Post-EOI
Preinfusion
Preinfusion
DOV
DOV
CX-2009 Plasma PK a
X
X
X
X
X
X
X
X
X
CX-2009 Serum ADA b
X
X
X
X
X
X
X
Notes: Part C2 cycle length is 28 days. Sparse blood samples will be collected to characterize the PK of the Probody therapeutic in all subjects. Blood samples will be collected 
to assess the extent of ADA response to the Probody therapeutic. Actual times of CX-2009 dosing and PK/ADA collection must be recorded.
a PK samples will be drawn at the following times: 
• Cycle 1 Day 1: preinfusion, 15 (r10) minutes post-EOI 
• Cycle 1 Day 15: preinfusion 
• Cycle 2 Day 1: preinfusion (up to 2 days before infusion), 15 (r10) minutes post-EOI
• Cycle 2 Day 15: preinfusion (up to 1 day before infusion)
• Cycles 3, 4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion (up to 2 days before infusion)
• EOT (DOV)
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009
b ADA samples will be drawn at the following times (to coincide with PK collections):
• Cycle 1 Day 1: preinfusion 
• Cycle 1 Day 15: preinfusion 
• Cycle 2 Day 1: preinfusion
• Cycle 2 Day 15: preinfusion (up to 1 day before infusion)
• Cycles 3, 4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion (up to 2 days before infusion)
• EOT (DOV)
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009
ADA = antidrug antibody; DOV = day of visit; EOI = end of infusion; EOT = end of treatment; PK = pharmacokinetic.


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Table 22.
Schedule of PK and ADA Assessments: Part D1
Page 1 of 2
Period/Procedure
Cycle 1
Cycle 2
Cycles 3, 4, 
6, 8 & Every 
8 Cycles 
Thereafter
EOT
Follow-up
Visit 1
Cycle Day
1
2
3
8
15
1
8
15
1
Time of Draw
Preinfusion
Post-
EOI
DOV
DOV
DOV
PreinfusionPreinfusion
Post-
EOI
DOV Preinfusion Preinfusion DOV
DOV
CX-2009 Plasma PK a
X
X
X
X
X
X
X
X
X
X
X
X
X
CX-2009 Serum ADA b
X
X
X
X
X
X
X
CX-072 PK c
X
X
X
X
X
X
X
X
X
CX-072 ADA d
X
X
X
X
X
X
X
Notes: Part D1 cycle length is 28 days. Serial blood samples will be collected to characterize the PK of the CX-2009 and CX-072 and all drug-related moieties in all subjects. 
Blood samples will be collected to assess the extent of ADA response to the Probody therapeutic. Actual times of CX-2009 and CX-072 dosing and PK/ADA collection must be 
recorded.
a CX-2009 PK samples will be drawn at the following times: 
• Cycle 1 Day 1: preinfusion, 15 (r10) minutes post-EOI, and 1 hour (r10 minutes) post-EOI
• Cycle 1 Day 2 (r6 hours)
• Cycle 1 Day 3 (r12 hours)
• Cycle 1 Day 8 (r1 day)
• Cycle 1 Day 15 (r1 day)
• Cycle 2 Day 1: preinfusion, 15 (r10) minutes post-EOI, and 1 hour (r10 minutes) post-EOI
• Cycle 2 Day 8 (r2 days)
• Cycle 2 Day 15 (r1 days): preinfusion
• Cycles 3,4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion (up to 2 days before infusion)
• EOT (DOV)
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009 or CX-072, whichever comes later
b CX-2009 ADA samples will be drawn at the following times (to coincide with PK collections):  
• Cycle 1 Day 1: preinfusion 
• Cycle 1 Day 15: preinfusion
• Cycle 2 Day 1: preinfusion
• Cycle 2 Day 15: preinfusion
• Cycles 3, 4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion (up to 2 days before infusion)
• EOT (DOV)
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009 or CX-072, whichever comes later


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Table 22.
Schedule of PK and ADA Assessments: Part D1
Page 2 of 2 
c CX-072 PK samples will be drawn at the following times:
• Cycle 1 Day 1: preinfusion, 15 (r10) minutes post-EOI
• Cycle 1 Day 15: preinfusion
• Cycle 2 Day 1: preinfusion, 15 (r10) minutes post-EOI
• Cycle 2 Day 15: preinfusion
• Cycles 3, 4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion
• EOT
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009 or CX-072, whichever comes later
d CX-072 ADA samples will be drawn at the following times (to coincide with PK collections):
• Cycle 1 Day 1: preinfusion
• Cycle 1 Day 15: preinfusion
• Cycle 2 Day 1: preinfusion
• Cycle 2 Day 15: preinfusion
• Cycles 3, 4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion
• EOT
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009 or CX-072, whichever comes later
ADA = antidrug antibody; D = day; DOV = day of visit; EOI = end of infusion; EOT = end of treatment; PK = pharmacokinetic.


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Table 23.
Schedule of PK and ADA Assessments: Part D2
Period/Procedure
Cycle 1
Cycle 2
Cycles 3, 4, 6, 8 & 
Every 8 Cycles 
Thereafter
EOT
Follow-up
Visit 1
Cycle Day
1
15
1
15
1
Time of Draw
Preinfusion
Post-EOI
Preinfusion
Preinfusion
Post-EOI
Preinfusion
Preinfusion
DOV
DOV
CX-2009 Plasma PK a
X
X
X
X
X
X
X
X
X
CX-2009 Serum ADA b
X
X
X
X
X
X
X
CX-072 PK a
X
X
X
X
X
X
X
X
X
CX-072 ADA b
X
X
X
X
X
X
X
Notes: Part D2 cycle length is 28 days. Sparse blood samples will be collected to characterize the PK of the Probody therapeutic in all subjects. Blood samples will be collected to 
assess the extent of ADA response to the Probody therapeutic. Actual times of CX-2009 and CX-072 dosing and PK/ADA collection must be recorded.
a CX-2009 and CX-072 PK samples will be drawn at the following times: 
• Cycle 1 Day 1: preinfusion, 15 (r10) minutes post-EOI
• Cycle 1 Day 15: preinfusion (up to 1 day before infusion)
• Cycle 2 Day 1: preinfusion (up to 2 days before infusion), 15 (r10) minutes post-EOI
• Cycle 2 Day 15: preinfusion (up to 1 day before infusion)
• Cycles 3, 4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion (up to 2 days before infusion)
• EOT (DOV)
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009 or CX-072, whichever comes later
b CX-2009 and CX-072 ADA samples will be drawn at the following times (to coincide with PK collections): 
• Cycle 1 Day 1: preinfusion
• Cycle 1 Day 15: preinfusion
• Cycle 2 Day 1: preinfusion
• Cycle 2 Day 15: preinfusion
• Cycles 3, 4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion
• EOT (DOV)
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009 or CX-072, whichever comes later
ADA = antidrug antibody; DOV = day of visit; EOI = end of infusion; EOT = end of treatment; PK = pharmacokinetic.


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Table 24.
Schedule of PK and ADA Assessments: Part E1
Page 1 of 2
Period/Procedure
Cycle 1
Cycles 2, 4, 6, 8 
& Every 
8 Cycles 
Thereafter
Cycle 3
EOT
Follow-up
Visit 1
Cycle Day
1
2
3
8
15
1
1
8
15
Time of Draw
Preinfusion
Post-
EOI
DOV
DOV
DOV
DOV
Preinfusion
Preinfusion
Post-
EOI
DOV
DOV
DOV
DOV
CX-2009 Plasma PK a
X
X
X
X
X
X
X
X
X
X
X
X
X
CX-2009 Serum ADA b
X
X
X
X
X
CX-072 PK c
X
X
X
X
X
X
X
CX-072 ADA d
X
X
X
X
X
Notes: Part E1 cycle length is 21 days. Serial blood samples will be collected to characterize the PK of the CX-2009 and CX-072 and all drug-related moieties in all subjects. 
Blood samples will be collected to assess the extent of ADA response to the Probody therapeutic. Actual times of CX-2009 and CX-072 dosing and PK/ADA collection must be 
recorded.
a PK samples will be drawn at the following times: 
• Cycle 1 Day 1: preinfusion, 15 (r10) minutes post-EOI, and 1 hour (r10 minutes) post-EOI
• Cycle 1 Day 2 (r6 hours)
• Cycle 1 Day 3 (r12 hours)
• Cycle 1 Day 8 (r1 day)
• Cycle 1 Day 15 (r1 day)
• Cycles 2, 4, 6, 8, and every 8 cycles thereafter: Day 1: preinfusion (up to 2 days before infusion)
• Cycle 3 Day 1: preinfusion (up to 2 days before infusion), 15 (r10) minutes post-EOI, and 1 hour (r10 minutes) post-EOI
• Cycle 3 Day 8 (r2 days)
• Cycle 3 Day 15 (r2 days) 
• EOT (DOV)
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009 or CX-072, whichever comes later
b ADA samples will be drawn at the following times (to coincide with PK collections):  
• Cycles 1, 2, 3, 4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion (up to 2 days before infusion)
• EOT (DOV)
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009 or CX-072, whichever comes later


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Table 24.
Schedule of PK and ADA Assessments: Part E1
Page 2 of 2
c PK samples will be drawn at the following times:  
• Cycle 1 Day 1: preinfusion, 15 (r10) minutes post-EOI
• Cycles 2, 4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion 
• Cycle 3 Day 1: preinfusion, 15 (r10) minutes post-EOI
• EOT 
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009 or CX-072, whichever comes later
d ADA samples will be drawn at the following times (to coincide with PK collections):  
• Cycles 1, 2, 3, 4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion (up to 2 days before infusion)
• EOT (DOV)
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009 or CX-072, whichever comes later
ADA = antidrug antibody; D = day; DOV = day of visit; EOI = end of infusion; EOT = end of treatment; PK = pharmacokinetic.


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Amendment 7, 20 February 2020
Table 25.
Schedule of PK and ADA Assessments: Part E2
Period/Procedure
Cycle 1
Cycles 2, 4, 6, 8 & 
Every 8 Cycles 
Thereafter
Cycle 3
EOT
Follow-up Visit 1
Cycle Day
1
1
1
Time of Draw
Preinfusion
Post-EOI
Preinfusion
Preinfusion
Post-EOI
DOV
DOV
CX-2009 Plasma PK a
X
X
X
X
X
X
X
CX-2009 Serum ADA b
X
X
X
X
X
CX-072 PK c
X
X
X
X
X
X
X
CX-072 ADA d
X
X
X
X
X
Notes: Part E2 cycle length is 21 days. Sparse blood samples will be collected to characterize the PK of the Probody therapeutic in all subjects. Blood samples will be collected to 
assess the extent of ADA response to the Probody therapeutic. Actual times of CX-2009 and CX-072 dosing and PK/ADA collection must be recorded.
a PK samples will be drawn at the following times: 
• Cycle 1 Day 1: preinfusion, 15 (r10) minutes post-EOI
• Cycles 2, 4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion (up to 2 days before infusion)
• Cycle 3 Day 1: preinfusion (up to 2 days before infusion), 15 (r10) minutes post-EOI
• EOT (DOV)
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009 or CX-072, whichever comes later
b ADA samples will be drawn at the following times (to coincide with PK collections): 
• Cycles 1, 2, 3, 4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion (up to 2 days before infusion)
• EOT (DOV)
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009 or CX-072, whichever comes later
c PK samples will be drawn at the following times: 
• Cycle 1 Day 1: preinfusion, 15 (r10) minutes post-EOI
• Cycles 2, 4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion (up to 2 days before infusion)
• Cycle 3 Day 1: preinfusion (up to 2 days before infusion), 15 (r10) minutes post-EOI
• EOT (DOV)
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009 or CX-072, whichever comes later
d ADA samples will be drawn at the following times (to coincide with PK collections): 
• Cycles 1, 2, 3, 4, 6, 8, and every 8 cycles thereafter: Day 1 preinfusion (up to 2 days before infusion)
• EOT (DOV)
• Follow-up Visit 1: Once any time >90 days after the last dose of CX-2009 or CX-072, whichever comes later
ADA = antidrug antibody; DOV = day of visit; EOI = end of infusion; EOT = end of treatment; PK = pharmacokinetic.


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Appendix C:
Synopsis of the mTPI-2 Design
The modified toxicity probability interval 2 (mTPI-2) design (Guo 2017) is an interval-based
Phase 1 dose-finding design for guiding subject allocation from observed safety outcomes at
different dose levels, and deciding the maximum tolerated dose (MTD) at the end of the trial. It
is an improvement over the mTPI design (Ji 2010, Ji 2013, Yang 2015).
The mTPI design assesses the probabilities that the toxicity rate pi of dose level ݅falls into 
3 intervals (0, pT – İ1), (pT – İ1, pT İ2), and (pT İ2, 1), where pT is the target toxicity 
probability (say, pT = 0.3) for the MTD, İ1 DQGİ2 specify the length of toxicity interval. For 
example, when pT = İ1 = DQGİ2 = 0.05, the 3 toxicity intervals are (0.24), (0.25, 0.35), 
and (0.36, 1) and represent scenarios of underdosing, proper dosing, and overdosing. Similarly, 
when pT = İ1 = DQGİ2 = 0.05, the respective toxicity intervals are (0.14), (0.15, 0.25), 
and (0.26, 1). The mTPI-2 design selects the interval with the maximum probability and 
recommends decision to escalate, stay at the current dose level, or de-escalate, accordingly. In 
the previous example, if (0.25, 0.35) has the maximum probability, the design recommends to 
stay at the current dose level.
The mTPI-2 design improves over the mTPI design by blunting the Ockham’s razor that leads to 
some statistically sound, but practically undesirable, decisions in the original mTPI design. Case 
in point: with a target toxicity probability of pT = 0.3, the original mTPI design would 
recommend no dose change even if 3 of 6 subjects experienced dose-limiting toxicities (DLTs) at 
a given dose. To improve upon the original mTPI design, mTPI-2 divides the intervals 
(0, pT – İ1) and (pT İ2, 1) into shorter subintervals and makes recommendations based on these 
finer subintervals. The simulation study by Guo et al (Guo 2017) has shown that the mTPI-2
design minimizes the risk of wrong dose allocations, particularly with small-sample inferences 
common in dose-finding studies.
Both mTPI and mTPI-2 designs are transparent and user-friendly to both statisticians and 
clinicians, as all the decisions can be tabulated for examination prior to the trial. Figure 6 and 
Figure 7 are dose-finding decision tables for up to 14 subjects with target toxicity probability of 
30.0% and 20.0%, respectively. In these tables, the columns represent the number of subjects
treated at the current dose and rows denote the number of subjects experiencing DLT at that 
dose. The table enumerates all the possible dose-finding decisions, and therefore can be used to 
design and conduct the trial conveniently.


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Figure 6.
Decision Table for mTPI-2 Cohort (Target Toxicity Probability = 30.0%)
A decision table of the mTPI-2 design, with 14 subjects, the target probability of ݌்= 0.3 and 2 values ߝଵ= ߝଶ= 0.05.
D = de-escalate to a lower dose; DLT = dose-limiting toxicity; DU = de-escalate to a lower dose and the current dose will never be used again in the study; E = escalate to the next
higher dose; mTPI-2 = modified toxicity probability interval 2; S = stay at the same dose.


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Figure 7.
Decision Table for mTPI-2 Cohort (Target Toxicity Probability = 20.0%)
A decision table of the mTPI-2 design, with 14 subjects, the target probability of ݌்= 0.2 and 2 values ߝଵ= ߝଶ= 0.05.
D = de-escalate to a lower dose; DLT = dose-limiting toxicity; DU = de-escalate to a lower dose and the current dose will never be used again in the study; E = escalate to the next 
higher dose; mTPI-2 = modified toxicity probability interval 2; S = stay at the same dose.
*: If at the first dose level, users can choose to early-terminate the study or not based on their own discretion.


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Appendix D:
Data Safety Monitoring Board
A Data and Safety Monitoring Board (DSMB) has been established for the study. The DSMB 
will consist of individuals with pertinent expertise in clinical trials in oncology, immunology, 
and statistics who will review, on a regular basis, accumulating safety data from this ongoing 
study. The DSMB will also be notified of Module amendments. The DSMB will be charged with 
responsibility to advise CytomX Therapeutics, Inc. with regard to:
•
The continuing safety of current and future participants in the study; and
•
The continuing validity and scientific merit of the study. 
The DSMB will convene every 6 months in accord with meetings scheduled to review the 
overall CX-2009 program; a change in the frequency of meetings will be dictated by the 
availability and severity of ongoing safety information. Meetings will be held with the appointed 
representatives of the Statistical and Medical Groups from CytomX Therapeutics, Inc. The 
DSMB will review all safety information to determine whether the study will continue 
unchanged or whether Module modifications are required to ensure subject safety. 
Recommendations for closing should be on the basis of excessive toxicity in the statistics report 
or the aggregated safety data. This determination will be documented by a letter from the DSMB. 
In the event that the DSMB advises a major change in the study design or conduct, such as early 
termination, this advice will be transmitted to Sponsor Steering Committee. The Sponsor 
Steering Committee will consist of representatives of senior management of CytomX
Therapeutics, Inc., including Chief Medical Officer, Chief Legal Counsel, and Chief Executive 
Officer.
The DSMB will consist of at least 3 members. Data Safety Monitoring Board member(s) who 
withdraw prior to completion of the project will be replaced. Should it become necessary to 
expand the number of DSMB members, CytomX Therapeutics, Inc. will appoint additional 
members. The responsibilities of the DSMB for this trial will end 6 months after last subject is 
enrolled or upon submission of a final study report.


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Appendix E:
Safety Review Committee
A Safety Review Committee (SRC) has been established for the study. The SRC will consist of 
selected Investigators from the trial and representatives from CytomX Therapeutics, Inc. who 
will review on a regular basis, the cumulative safety data from each cohort in the study in order 
to:
•
Approve dose escalation to the next cohort in Part A of the study;
•
Recommend modifications to the dose or schedule as it pertains to subject safety; or
•
Recommend modifications to the Module related to subject oversight (eg, additional safety 
monitoring, changes to inclusion/exclusion criteria).
Actions taken regarding dose escalation or amendments to the Module will be documented and 
stored in the trial master file for the study.


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Appendix F:
Adjusted Ideal Body Weight Calculation
The total dose of drug will be calculated based on each subject’s adjusted body weight using the 
following formula:
Adjusted Ideal Body Weight (AIBW)
IBW a + 0.4 (Actual Weight-IBW a)
Where:
Ideal Body Weight (IBW)
IBW a (male) = 0.9H1 – 88
IBW a (female) = 0.9H1 – 92
a H = height in cm; W = weight in kg.


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Appendix G:
List of Concomitant Medications Representing Inhibitors of CYP3A
Table 26.
List of Concomitant Medications Representing Inhibitors of CYP3A
CYP 
Enzymes
Strong Inhibitors
Moderate Inhibitors
Weak Inhibitors
CYP3A
Boceprevir, cobicistat, conivaptan, 
danoprevir and ritonavir, elvitegravir and 
ritonavir, grapefruit juice, indinavir and 
ritonavir, itraconazole, ketoconazole, 
lopinavir and ritonavir, paritaprevir and 
ritonavir and (ombitasvir and/or 
dasabuvir), posaconazole, ritonavir, 
saquinavir and ritonavir, telaprevi, 
tipranavir and ritonavir, troleandomycin, 
voriconazole, clarithromycin, diltiazem, 
idelalisib, nefazodone, nelfinavir
Aprepitant, cimetidine,
ciprofloxacin, 
clotrimazole, crizotinib, 
cyclosporine, 
dronedarone, 
erythromycin, fluconazole, 
fluvoxamine, imatinib, 
tofisopam, verapamil
Chlorzoxazone, cilostazol, 
fosaprepitant, 
istradefylline, ivacaftor, 
lomitapide, ranitidine, 
ranolazine, tacrolimus,
ticagrelor
CYP = cytochrome P450.
Source: United States Food and Drug Administration web site: Drug Development and Drug Interactions: Table of Substrates, 
Inhibitors and Inducers: Table 3-2. Available at:  https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-
and-drug-interactions-table-substrates-inhibitors-and-inducers#table. Accessed 19 November 2019.


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Appendix H:
List of Concomitant Medications Requiring Avoidance 
Table 27.
List of Concomitant Medications Requiring Avoidance
CYP 
Enzymes
Sensitive Substrates
Substrates With Narrow 
Therapeutic Range
CYP3A
Alfentanil, aprepitant, budesonide, buspirone, conivaptan, 
darifenacin, darunavir, dasatinib, dronedarone, eletriptan, 
eplerenone, everolimus, felodipine, indinavir, fluticasone, 
lopinavir, lovastatin, lurasidone, maraviroc, midazolam, 
nisoldipine, quetiapine, saquinavir, sildenafil, simvastatin, 
sirolimus, tolvaptan, tipranavir, triazolam, vardenafil
Alfentanil, astemizole, cisapride, 
cyclosporine, dihydroergotamine, 
ergotamine, fentanyl, primozide, 
quinidine, sirolimus, tacrolimus, 
terfenadine
CYP = cytochrome P450.
Source: United States Food and Drug Administration web site: Drug Development and Drug Interactions: Table of Substrates, 
Inhibitors and Inducers: Table 3-1. Available at: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-
and-drug-interactions-table-substrates-inhibitors-and-inducers#table3-1. Accessed 19 November 2019.


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Appendix I:
Description of Criteria to Assess CD166 Immunohistochemistry Staining
High cluster of differentiation 166 (CD166) expression is defined as immunohistochemistry 
(IHC) staining of t50.0% of tumor cell staining at 3+ intensity. Only membrane-associated 
staining within tumor cells will be evaluated. The cytoplasmic staining in tumor cells or the 
staining in non-tumor cells (ie, normal epithelium or immune cells) will not be considered for 
scoring. Scoring will be attributed following a pathologist’s visual assessment of the 
membrane-associated staining intensity on tumor cells using the following criteria: 0 = no
staining, 1+ = weak staining, 2+ = moderate staining, 3+ = strong staining. Subjects (except 
those with hormone receptor-positive/human epidermal growth factor receptor 2-negative breast 
cancer) will be required to have demonstrated high CD166 expression (3+) in archival tumor 
tissue, as measured by a qualified IHC assay using a clinical trial assay performed in a central 
Clinical Laboratory Improvement Amendments of 1998 (CLIA)-certified laboratory.


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Appendix J:
Prior Lines of Therapy Counting Rule Guidance
Therapy administered in the neoadjuvant or adjuvant setting do not count as a regimen to 
determine eligibility in this module. Therapy(ies) following surgery for locally advanced breast 
cancer (BC) (eg, Stage IIIA with T3 N1 M0) will count as adjuvant therapy. All classes of 
systemic antineoplastic drugs count when administered for advanced or metastatic BC 
(hormonal, biological, cytotoxic, immunotherapeutic, antibody drug conjugates, 
chemo-radiation, etc) will count as a regimen, whether administered as single-agent or in 
combination.
Following are examples of what does NOT count as a separate regimen:
•
Substitution within a class due to toxicity;
•
Retreatment with the same agent without interval progression;
•
Continuation of 1 drug within a combination regimen;
•
Planned sequential dosing (1 drug followed by a second drug without interval progression); 
or 
•
Local therapy (eg, intratumor injection).

SAP_001.pdf: 
CTMX-M-2009-001 
Statistical Analysis Plan 
A Phase 1-2, Open-Label, Dose-Finding, Proof of Concept, First-in-Human Study to Evaluate 
the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CX-2009 in Adults With 
Metastatic or Locally Advanced Unresectable Solid Tumors (PROCLAIM-CX-2009) 
NCT# NCT03149549 
07/October/2020 


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Statistical Analysis Plan
SPONSOR: 
CytomX Therapeutics, Inc.
PROTOCOL TITLE:
A Phase 1-2, Open-Label, Dose-Finding, Proof of Concept, 
First-in-Human Study to Evaluate the Safety, Tolerability, 
Pharmacokinetics, and Pharmacodynamics of CX-2009 in Adults 
with Metastatic or Locally Advanced Unresectable Solid Tumors
STUDY CODE:
CTMX-M-2009-001
VERSION:
2.0 (07OCT2020)
The undersigned certify that they have read, reviewed and approved this document.
Authors (IDDI): Michael Hussey, DrPH - Managing Director, IDDI Inc.
CytomX Representative: Claire Sherman, Executive Director, Biostatistics


 
 
 
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Table of Contents 
 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ...................................... 4 
1. 
PURPOSE ..................................................................................................... 6 
2. 
STUDY POPULATION .................................................................................... 6 
3. 
STUDY OBJECTIVES ..................................................................................... 6 
3.1 
Primary Objectives ................................................................................... 6 
3.2 
Secondary Objectives ............................................................................... 7 
3.3 
Exploratory Objectives .............................................................................. 9 
4. 
STUDY METHODS ....................................................................................... 10 
4.1 
Overview of Study Design ....................................................................... 10 
4.2 
Subject Eligibility and Enrollment ............................................................. 12 
4.3 
Study Periods and Follow-Up ................................................................... 12 
4.4 
Administration of the study drug .............................................................. 13 
4.5 
Discontinuation of Subjects from Treatment .............................................. 14 
5. 
STUDY ENDPOINTS .................................................................................... 14 
5.1.1 
Primary Safety Domains ................................................................... 14 
5.1.2 
Primary Efficacy Endpoint ................................................................. 14 
5.1.3 
Secondary Efficacy .......................................................................... 15 
6. 
DATA CAPTURE AND PROCESSING ............................................................. 15 
7. 
ANALYSIS AND REPORTING....................................................................... 15 
7.1 
Interim Analyses .................................................................................... 15 
7.1.1 
Safety Review Committee (SRC) ....................................................... 15 
7.1.2 
Data Safety Monitoring Board (DSMB) ............................................... 15 
7.1.3 
Final Analysis .................................................................................. 16 
8. 
SAMPLE SIZE DETERMINATION ................................................................. 16 
9. 
DEFINITION OF POPULATIONS .................................................................. 16 
9.1 
Safety Analysis Population (SP) ............................................................... 16 
9.2 
Response Evaluable Population (REP) ....................................................... 16 
10. 
GENERAL STATISTICAL CONSIDERATIONS............................................. 16 
10.1 
General Statistical Methodology ............................................................... 16 
10.1.1 
Handling of Missing Data .................................................................. 17 
10.1.2 
Derived and Computed Variables ....................................................... 18 
11. 
SUBJECT CHARACTERISTICS AND DEMOGRAPHICS ................................ 20 
11.1 
Enrollment and Disposition of Subjects ..................................................... 20 
11.2 
Protocol Deviations ................................................................................ 20 
11.3 
Demographics and Baseline Characteristics ............................................... 20 
12. 
SAFETY AND TOLERABILITY ANALYSIS .................................................. 21 
12.1 
Adverse Events and Serious Adverse Events .............................................. 21 
12.2 
Study Drug Administration and Exposure .................................................. 24 
12.3 
Concomitant Medications ........................................................................ 24 
12.4 
Clinical Laboratory Tests ......................................................................... 25 


 
 
 
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12.5 
Other Safety Measures ........................................................................... 25 
12.5.1 
Vital Signs ...................................................................................... 25 
12.5.2 
ECGs ............................................................................................. 26 
13. 
EFFICACY ANALYSIS .............................................................................. 26 
13.1.1 
Primary Efficacy Endpoint ................................................................. 26 
13.1.2 
Secondary Efficacy Endpoints............................................................ 28 
13.1.3 
Efficacy Measures during Follow-up ................................................... 30 
13.1.4 
Eastern Cooperative Oncology Group (ECOG) Performance Status ......... 30 
14. 
PHARMACOKINETIC, IMMUNOGENICITY, AND PHARMACODYNAMIC 
ASSESSMENTS .................................................................................................. 31 
14.1 
PK Assessments ..................................................................................... 31 
14.2 
Immunogenicity Assessments .................................................................. 31 
15. 
EXPLORATORY ANALYSES ...................................................................... 31 
15.1 
Pharmacodynamics and Exploratory Biomarkers ........................................ 31 
15.2 
Additional Exploratory Analyses ............................................................... 31 
16. 
REFERENCES .......................................................................................... 32 
 
 
 


 
 
 
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List of Abbreviations and Definition of Terms 
Abbreviation Definition 
AE 
adverse event 
ATC 
Anatomical Therapeutic Chemical 
CI 
confidence interval  
CR 
complete response 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLT 
dose limiting toxicity 
DOR 
duration of response 
DSMB 
data and safety monitoring board 
ECG 
electrocardiogram 
FDA 
Food and Drug Administration 
ICF 
informed consent form 
IR 
infusion reaction 
IV  
intravenous 
IWRS 
interactive web response system 
MedDRA 
medical dictionary for regulatory activities 
MTD 
maximum tolerated dose 
NCI 
National Cancer Institute 
NE 
not evaluable 
ORR 
objective response rate 
OS 
overall survival 
PD 
progressive disease 
PD-1 
programmed cell death 1 
PD-L1 
programmed cell death ligand 1 
PFS 
progression-free survival 
PK 
pharmacokinetic 
PR 
partial response 
PT 
preferred term 
q 21 days 
every 21 days 
RECIST 
Response Evaluation Criteria in Solid Tumors 


 
 
 
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Abbreviation Definition 
REP 
response evaluable population 
RP2D 
recommended Phase 2 dose 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
standard deviation 
SD 
stable disease 
SOC 
system organ class 
SP 
safety population 
SRC 
safety review committee 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
TMTB 
total measured tumor burden 
TTR 
time to response 
WHODrug 
World Health Organization Drug Dictionary 
 
 
 


 
 
 
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1. 
Purpose 
This Statistical Analysis Plan (SAP) describes the statistical methodology and data 
handling for CytomX Therapeutics, Inc. protocol module number CTMX-M-2009-
001 (A Phase 1-2, Open-Label, Dose-Finding, Proof of Concept, First-in-Human 
Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and 
Pharmacodynamics of CX-2009 in Adults with Metastatic or Locally Advanced 
Unresectable Solid Tumors). The analysis specified in this SAP will be used to 
support safety review committee (SRC) and data and safety monitoring board 
(DSMB) analyses, publications, and FDA submissions. The proposed analyses may 
not be carried out if the sample size is not adequate. 
The ICH guideline E3 “Structure and Content of Clinical Study Reports” was used as 
a guide to the writing of the plan. 
This SAP is based on the following study documents: 
x 
Protocol Core Amendment 01, 11 November 2016 
x 
Protocol Module Amendment 06, 09 August 2017,  
x 
Protocol Substudy V1.0, 04 May 2018 
x 
Annotated Case Report Forms 
The enrollment in CTMX-M-2009-001 was stopped by sponsor decision as of 07 July 
2020, with a final enrollment of XX subjects into Parts A, A2, B, and C1. 
2. 
Study Population 
This study of CX-2009 will enroll adult subjects with advanced solid tumors in the 
following indications: breast carcinoma (BC), castration-resistant  prostate  
carcinoma (CRPC),  non-small  cell  lung  carcinoma (NSCLC), epithelial ovarian  
carcinoma (eOC),  endometrial  carcinoma (EC),  head  and  neck  squamous  cell  
carcinoma (HNSCC),  or cholangiocarcinoma (CCC). These  7  tumor  types  have 
been  selected  for  their  known  high  levels  of CD166 expression and sensitivity 
to MTIs. Prior to the decision to stop enrolment in the study, approximately 563 
subjects  were planned to be enrolled into the study. Inclusion and exclusion criteria 
are detailed in Sections 4.1 and 4.2 of the protocol.  
3. 
Study Objectives 
The study objectives as per the protocol are presented below.  
3.1 
Primary Objectives 
Part A – CX-2009 Monotherapy: Every 21-Day Dosing Regimen 
The primary objective of Part A is to determine the safety profile of CX-2009, the 
MTD/RP2D, and the DLTs of CX-2009 when administered intravenously (IV) every 
21 days as monotherapy to subjects with selected advanced or recurrent solid 
tumors. 
Part A2 – CX-2009 Monotherapy: Every 21-Day Dosing Regimen 
The primary objectives of Part A2 are to determine the following in subjects treated 
with CX-2009 every 21 days: 
x 
Characterize the protease activity and measure the cleavage of CX-2009 in 
tumor biopsies and peripheral blood in subjects with demonstrated high 
tumor expression of CD166 by IHC; and 


 
 
 
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x 
Obtain additional characterization of the safety CX-2009 when administered 
as monotherapy at dose levels evaluated in Part A. 
Part B – CX-2009 Monotherapy: Every 21-Day Dosing Regimen 
The primary objective of Part B is to evaluate the efficacy of CX-2009 when 
administered IV every 21 days as monotherapy at the MTD/RP2D (as defined in 
consideration of available data from Part A and Part A2) in subjects with selected 
advanced or recurrent solid tumors with demonstrated high tumor expression of 
CD166 by IHC. Efficacy will be assessed on the basis of the ORR by the Response 
Evaluation Criteria in Solid Tumours (RECIST) Version 1.1.  
Part C1 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen 
The primary objective of Part C1 is to determine the safety profile of CX-2009, the 
MTD/RP2D, and the DLTs of CX-2009 when administered IV every 14 days as 
monotherapy to subjects with selected advanced or recurrent solid tumors with 
demonstrated high expression of CD166 by IHC.  
3.2 
Secondary Objectives 
Part A – CX-2009 Monotherapy: Every 21-Day Dosing Regimen 
The secondary objectives of Part A are to determine the following in subjects treated 
with CX-2009 every 21 days:  
x 
Evaluate  preliminary  efficacy  in  subjects  treated  with  CX-2009  as  
monotherapy  on  the basis of:  
o 
ORR by the RECIST Version 1.1; 
o 
Time to tumor response (TTR);    
o 
Duration of response (DOR);    
o 
Progression-free survival (PFS); and    
o 
Overall survival (OS);  
 
x 
Characterize the pharmacokinetics (PK) of CX-2009 including the following 
analytes:  
 
o 
Intact CX-2009 (referring to the prodrug form of CX-2009 ± DM4);  
o 
Total CX-2009 (intact and activated forms of CX-2009 ±DM4);  
o 
Total CX-2009-conjugated DM4 (antibody conjugated-DM4);  
o 
Free DM4;  
o 
DM4-Me – a DM4 metabolite with potent cytotoxic activity; and   
 
x 
Assess the incidence antidrug antibody (ADA) formation to CX-2009. 
Part A2 – CX-2009 Monotherapy: Every 21-Day Dosing Regimen 
The secondary objectives of Part A2 are to determine the following in subjects with 
demonstrated high tumor expression of CD166 and treated with CX-2009 every 21 
days:  
x 
Evaluate  preliminary  efficacy  in  subjects  treated  with  CX-2009  as  
monotherapy  on  the basis of:  
o 
ORR by the RECIST Version 1.1; 
o 
TTR;    
o 
DOR;    
o 
PFS; and    
o 
OS;  
 


 
 
 
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x 
Characterize the PK of CX-2009 including the following analytes:   
o 
Intact CX-2009 (referring to the prodrug form of CX-2009 ± DM4);  
o 
Total CX-2009 (intact and activated forms of CX-2009 ±DM4);  
o 
Total CX-2009-conjugated DM4 (antibody conjugated-DM4);  
o 
Free DM4;  
o 
DM4-Me; and   
x 
Assess the incidence ADA formation to CX-2009. 
 
Part B – CX-2009 Monotherapy: Every 21-Day Dosing Regimen 
The secondary objectives of Part B are to determine the following in subjects with 
demonstrated high tumor expression of CD166 and treated with CX-2009 every 21 
days:  
x 
Obtain additional characterization of the safety of CX-2009 at the MTD/RP2D; 
x 
Evaluate  efficacy  in  subjects  treated  with  CX-2009  as  monotherapy  on  
the basis of:  
o 
DOR; 
o 
TTR;      
o 
PFS; and    
o 
OS;  
 
x 
Characterize the PK of CX-2009 with respect to the following analytes:   
o 
Intact CX-2009 (referring to the prodrug form of CX-2009 ± DM4);  
o 
Total CX-2009 (intact and activated forms of CX-2009 ±DM4);  
o 
Total CX-2009-conjugated DM4 (antibody conjugated-DM4);  
o 
Free DM4;  
o 
DM4-Me; and   
x 
Assess the incidence ADA formation to CX-2009. 
 
Part C1 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen 
The secondary objectives of Part C1 are to determine the following in subjects with 
demonstrated high tumor expression of CD166 and treated with CX-2009 every 14 
days:  
x 
Evaluate  preliminary efficacy  in  subjects  treated  with  CX-2009  as  
monotherapy  on  the basis of:  
o 
ORR by the RECIST Version 1.1; 
o 
TTR; 
o 
DOR;      
o 
PFS; and    
o 
OS;  
 
x 
Characterize the PK of CX-2009 with respect to the following analytes:   
o 
Intact CX-2009 (referring to the prodrug form of CX-2009 ± DM4);  
o 
Total CX-2009 (intact and activated forms of CX-2009 ±DM4);  
o 
Total CX-2009-conjugated DM4 (antibody conjugated-DM4);  
o 
Free DM4;  
o 
DM4-Me; and   
x 
Assess the incidence ADA formation to CX-2009. 
 


 
 
 
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3.3 
Exploratory Objectives  
Part A – CX-2009 Monotherapy: Every 21-Day Dosing Regimen 
The exploratory objectives of Part A are to determine the following in subjects treated 
with CX-2009 every 21 days: 
x 
Explore potential predictive markers associated with CX-2009 clinical activity 
such as CD166 expression in tumor specimens prior to and while receiving 
treatment; and 
x 
Characterize the protease activity in optional pretreatment tumor biopsies 
and activation of CX-2009 in optional on-treatment tumor biopsies and 
peripheral blood. 
 
Part A2 – CX-2009 Monotherapy: Every 21-Day Dosing Regimen 
The exploratory objectives of Part A2 are to determine the following in subjects 
treated with CX-2009 every 21 days: 
x 
Evaluate the relationship between CX-2009 dose and exposure, exploratory 
biomarkers, safety, and efficacy of CX-2009 as monotherapy in subjects with 
selected advanced or recurrent solid tumors with demonstrated high tumor 
expression of CD166; and 
x 
Explore potential predictive markers associated with CX-2009 clinical activity 
such as CD166 expression in tumor specimens from subjects with 
demonstrated high tumor expression of CD166 while receiving treatment.  
 
Part B – CX-2009 Monotherapy: Every 21-Day Dosing Regimen 
The exploratory objectives of Part B are to determine the following in subjects treated 
with CX-2009 every 21 days: 
x 
Explore potential predictive markers associated with CX-2009 clinical activity 
such as CD166 expression in tumor specimens prior to and while receiving 
treatment from subjects with demonstrated high tumor expression of CD166;  
x 
Measure the intact and activated CX-2009 in on-treatment tumor biopsies 
and peripheral blood; and  
x 
Characterize the protease activity in pretreatment tumor biopsies. 
 
Part C1 – CX-2009 Monotherapy: Every 14-Day Dosing Regimen 
The exploratory objectives of Part C1 are to determine the following in subjects 
treated with CX-2009 every 14 days: 
x 
Explore potential predictive markers associated with CX-2009 clinical activity 
such as CD166 expression in tumor specimens prior to and while receiving 
treatment; and 
x 
Characterize the activation of CX-2009 in optional on-treatment tumor 
biopsies and peripheral blood.  
 
 
 
 


 
 
 
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4. 
Study Methods 
4.1 
Overview of Study Design  
This is a Phase 1-2, open-label, multicenter, dose-finding, and proof of concept study 
for CX-2009 as  monotherapy  in  subjects  with  advanced  solid  tumors  in  selected 
indications.  
The study (as of Protocol Amendment 06) has 7 parts, as described below (Figure 
1).  Since the enrollment ended after Parts A, A2, B, and C1, the description is limited 
to those parts.  
Part A: Dose  escalation  and  determination  of  MTD/RP2D of the CX-2009 
monotherapy every 21-day dosing regimen (n79:  based on actual enrollment of 
initial cohorts and assumption of remaining cohorts and up to 38 total subjects 
enrolled into the mTPI-2 design cohort):  This part will initiate with accelerated dose 
titration  in  1  single-subject  cohort  (0.25  mg/kg  [mpk],  adjusted  ideal  body  
weight  [AIBW]), followed by a standard 3+3 design to determine the MTD, and end 
in a mTPI-2 design cohort with up to 38 subjects with demonstrated high CD166 
expression to determine the RP2D. The mTPI-2 design is a rule-based design similar 
to the 3+3 design and allows dose escalation/de-escalation. It is assumed to be of 
similar accuracy in determining the optimal dose as model-based design (Ji et al, 
2007) but allows a more flexible sample size. To understand the statistical rationale 
for the design, please refer to Section 9 and Appendix C of the CTMX-M-2009-001 
Protocol Module.  
Part A2: Additional enrollment into previously cleared CX-2009 monotherapy dose 
levels from Part A (n42) for every 21-day dosing regimen: This part will help inform 
selection of the optimal MTD/RP2D by requiring measurable disease, mandating 
biopsies to assess Probody therapeutic CX-2009 performance, and selecting for 
confirmed high CD166 expressing tumors by IHC. Additionally, the relationship 
between dose/exposure and safety as well as antitumor activity will further enhance 
MTD/RP2D selection by including more subjects for safety evaluation and selecting 
for confirmed high CD166 expression in tumors by IHC in Part A2. Part A2 will 
interrogate dose levels beginning at 4 mg/kg and up to the MTD/RP2D determined 
in Part A. The expression of CD166 will be evaluated on archival samples using a 
Clinical Laboratory Improvement Amendments of 1998 (CLIA)-validated IHC assay. 
Part B: Dose expansion (proof of concept) at the MTD/RP2D of CX-2009 
monotherapy every 21-day dosing regimen with proof of concept in selected tumor 
types (maximum n200):  This part will explore efficacy of CX-2009 by requiring 
measurable disease and selecting for confirmed high CD166 expressing tumors. Part 
B will enroll up to a total of 40 subjects in each of 1 or more of the 5 tumor types 
listed in Table 4 in the CTMX-M-2009-001 Protocol Module. Part B will only be 
initiated if, after the review of dose escalation data (Parts A and A2), an every 21-
day dosing regimen is considered for further development.  
Part C1: Dose escalation and determination of the MTD/RP2D of the CX-2009 
monotherapy every 14-day dosing regimen in subjects with high CD166 expression 
(n18):  The highest dose level tested in this clinical study for CX-2009 was 10 
mg/kg administered every 21 days, which successfully cleared the DLT evaluation 
period. The every 14-day dosing regimen equivalent of 10 mg/kg administered every 
21 days is 7 mg/kg. In order to provide an additional margin of safety coverage for 
Part C1, the starting dose will be 6 mg/kg, AIBW, administered every 14 days. The 
mTPI-2 design will be used to determine the MTD/RP2D for this schedule. The 
following cohort’s dose will be increased according to the defined dose escalation 


 
 
 
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rules to 8 mg/kg and then to 10 mg/kg based upon the observed safety tolerability 
profile as determined in consultation with the SRC. Prior to a dose escalation, a 
minimum of 3 evaluable subjects must be assessed per the mTPI-2 algorithm (Figure 
6 from the CTMX-M-2009-001 Protocol Module). The maximum dose level that will 
be tested in Part C1 will be 10 mg/kg. Part C1 will include up to 18 subjects. Subjects 
will be selected from the following indications: BC, NSCLC, or HNSCC.  
 
 
 


 
 
 
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Figure 1:  Study Design Schema: Parts A, A2, and B (every 21-day Dosing 
Regimen)  
 
Figure 2: Study Design Schema: Parts C1 and C2 (every 14-day Dosing Regimen) 
 
 
4.2 
Subject Eligibility and Enrollment 
At the time of the sponsor decision to stop enrollment into the study, there were 99 
subjects enrolled and treated in the study: 37 in Part A, 39 in Part A2, 10 in the 
mTPI-2 cohort, 3 in Part B, and 10 in Part C1.  
4.3 
Study Periods and Follow-Up 
The  study  is  divided  into  periods  with  associated  evaluations  and  procedures  
that  must  be performed  at  specific  time  points.  The  schedule  of  procedures in 
Appendix B of the CTMX-M-2009-001 Protocol Module summarizes the frequency  
and  timing  of  efficacy,  safety,  and  other  study  measurements.  Refer to the 
Common Core Document for a description of each procedure.   


 
 
 
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As with any Phase 1 study, an individual subject’s participation in the study is difficult 
to predict. It is estimated that average treatment will last approximately 6 months, 
followed by Follow-Up contact  every  3 to  6  months  for  another  1  to  2  years,  
or  as  long  as  the  subject  remains  alive (Figure 3). 
 
Figure 3:  Study Periods 
 
 
Following the completion of study treatment, subjects with progressive disease per 
RECIST v1.1 as measured by investigator assessment, will return for an end of 
treatment (EOT) Visit and then enter the Follow-Up Period for monitoring of survival. 
Subjects who for other reasons stop study drug treatment and subjects with stable 
disease, confirmed partial response, or confirmed complete response will enter the 
Follow-Up Period for monitoring of DOR and PFS.   
The study will be completed approximately 2 years from the date the last subject is 
enrolled or when the last subject has completed treatment and the last Follow-Up 
Visit.   
The EOT Visit will be conducted 30 days (±7 days) after the last infusion of CX-2009. 
Once a subject  experiences progressive  disease,  they  will  continue  to  be  
monitored  for  survival.  All subjects will return for Follow-Up Visits every 3 months 
after the EOT Visit for 1 year and then every 6 months to ensure resolution of 
toxicities and as applicable, confirm negative pregnancy status. During  the  EOT  
Visit,  subjects  will  be  followed  for  resolution  of  toxicity.  Women  of childbearing 
potential will undergo monthly pregnancy testing while on study drug and through 
50 days after the last dose of CX-2009, or 6 months after the last dose of CX-072, 
as applicable, whichever is later. Thereafter, Follow-Up Visits will be conducted for 
survival information and may be performed by telephone. 
4.4 
Administration of the study drug 
Treatment will be administered on an outpatient basis, with inpatient admission as 
needed for any treatment or monitoring outside of clinic hours or for management 
of significant acute toxicity.   


 
 
 
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CX-2009 will be administered at a dosage of 0.25, 0.5, 1, 2, 4, 5, 6, 7, 8, 9, 10 
mg/kg/dose (Adjusted Ideal Body Weight should be applied [Appendix F of the 
CTMX-M-2009-001 Protocol Module]).  
4.5 
Discontinuation of Subjects from Treatment 
Subject MUST discontinue the study drug for any of the following reasons:  
x 
The subject experiences clinically significant or confirmed (RECIST v1.1) 
disease progression (or irRECIST in Parts D1 and D2);  
x 
The subject is unwilling or unable to adhere to the Module;  
x 
The subject withdraws consent or is lost to follow-up;  
x 
The subject experiences an intercurrent illness that prevents further 
administration of study drug;  
x 
The subject requires new/other anti-cancer treatment;  
x 
The subject experiences a DLT or an adverse event related to study drug 
which precludes further administration of the study drug;  
x 
The subject experiences a prolonged treatment delay (as defined in Section 
5.5.4 of the CTMX-M-2009-001 Protocol Module);   
x 
The subject becomes pregnant, either prior to the first dose of study drug or 
at any time during treatment;   
x 
In the Investigator’s judgment, the subject should discontinue treatment;  
x 
Death of the subject; or  
x 
The Sponsor terminates the study.  
Subjects who discontinue study drug administration, for reasons other than TRAEs, 
may be replaced to ensure the minimum number of subjects required for DLT 
evaluation is enrolled. Subjects who have enrolled in the study and have withdrawn 
prior to receiving the first dose will be designated as screen failures. The reason for 
subject withdrawal must be documented in the electronic case report form (eCRF). 
5. 
Study Endpoints 
5.1.1 
Primary Safety Domains 
Incidence  and  nature  of  DLTs,  adverse  events,  serious  adverse  events, and 
adverse events of special interest,  as  well  as  physical examinations,  vital  sign  
measurements,  triplicate  electrocardiograms,  clinical  laboratory evaluations, and 
treatment discontinuation due to toxicity will be evaluated for safety assessment. 
5.1.2 
Primary Efficacy Endpoint 
The  primary  criteria  for  defining  evidence  of  anti-cancer  activity  and  also  for  
management  of subject care will be a clinical response as defined by RECIST 
(Version 1.1). ORR is the primary efficacy endpoint and ORR is defined as the 
proportion of subjects with complete response (CR) or partial response (PR) on two 
consecutive tumor assessments at least 4 weeks apart according to RECIST (RECIST 
v1.1). 
 
 
 


 
 
 
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5.1.3 
Secondary Efficacy  
Efficacy in this study will be explored in subjects treated with CX-2009 as 
monotherapy on the basis of:  
x 
TTR;  
x 
DOR;  
x 
PFS; and  
x 
OS. 
6. 
Data Capture and Processing 
Electronic data capture will be used for the study. Data will be recorded on source 
documentation at each study location and entered into the eCRF electronically by the 
study center personnel for each study subject. Data collected on each subject will be 
documented on the appropriate eCRF. Completed eCRFs are to be reviewed and 
electronically signed by the Investigator or his/her designee. 
7. 
Analysis and Reporting 
7.1 
Interim Analyses 
No formal interim analysis is planned.  
Administrative interim analyses on safety and efficacy or on PK, immunogenicity, 
and selected biomarkers may be performed several times prior to completion of the 
study in order to facilitate program decisions and to support study presentations or 
publications. 
7.1.1 
Safety Review Committee (SRC) 
A Safety Review Committee (SRC) has been established for the study. The SRC will 
consist of selected Investigators from the trial and representatives from CytomX who 
will review on a regular basis, approximately monthly, the cumulative safety data 
from each cohort in the study in order to:  
x 
Approve dose escalation to the next cohort in Part A, Part A2, or Part C1 of 
the study;  
x 
Recommend modifications to the dose or schedule as it pertains to subject 
safety; or  
x 
Recommend modifications to the protocol related to subject oversight (e.g., 
additional safety monitoring, changes to inclusion/exclusion criteria).  
The SRC will review safety data in conjunction with the Statistical and Medical Groups 
from CytomX.  
7.1.2 
Data Safety Monitoring Board (DSMB) 
A  Data  Safety  Monitoring  Board  (DSMB)  has  been  established  for  the  study.  
The DSMB will review table summaries and listings provided by IDDI in conjunction 
with the Statistical and Medical Groups from CytomX. Tables including, but not 
limited to, subject disposition, demographics and baseline characteristics, drug 
exposure, and AEs will be provided. Details on the DSMB are provided in Appendix 
D of the CTMX-M-2009-001 Protocol Module and in a separate DSMB charter. The 
DSMB will  make  recommendations  to  the  Sponsor,  who  will  make  ultimate  
decisions  regarding  study alteration or discontinuation. 


 
 
 
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7.1.3 
Final Analysis 
Data summaries, figures, and listings will be prepared as identified in this SAP 
following database lock. 
8. 
Sample Size Determination 
Enrollment into the study was stopped by the sponsor with 99 subjects enrolled and 
treated across Parts A, A2, B, and C1. The previously planned sample size was a 
maximum of 563 subjects enrolled across Parts A, A2, B, C1, C2, D1, and D2. No 
subjects were enrolled in Parts C2, D1, or D2 for this study. 
Refer to the CTMX-M-2009-001 Protocol Module for explanation on the original 
sample size calculation and statistical assumptions related to the design of the study.  
9. 
Definition of Populations 
Analysis populations for tabulations and figures are defined below for the following 
populations: safety analysis population (SP) and the response evaluable population 
(REP). Subject disposition will be based on the number of subjects providing signed 
informed consent.  
9.1 
Safety Analysis Population (SP)  
The safety analysis population includes all enrolled subjects who receive at least one 
dose of study drug. The safety analysis population is used for evaluating subject 
characteristics, treatment administration, safety endpoints and efficacy analyses 
related to PFS and OS. 
9.2 
Response Evaluable Population (REP) 
The response evaluable population includes all subjects in the safety analysis 
population who have an adequate baseline disease assessment and at least one post-
baseline disease assessment. The response-evaluable population is used for efficacy 
analyses related to objective response, including objective response rate (ORR), TTR, 
and DOR.  
10. General Statistical Considerations 
10.1 
General Statistical Methodology 
Data will be analyzed using SAS (Version 9.4 or higher). All consented subjects are 
identified by an 8-digit Subject Number where the first four digits represent site and 
the last four digits are the sequential enrollment within a site (e.g. 1234-0001). 
Descriptive statistics will be tabulated as follows:  
x 
Categorical data will be summarized in contingency tables presenting 
frequencies and percentages. 
x 
Continuous data will be summarized using number of non-missing values (n), 
mean, median, standard deviation, and median and range values. Where 
relevant, Q1 and Q3 may be presented.  
The tables will be created by dose level and by cancer type, unless otherwise 
specified. For tables by dose level, all available data from Parts A, A2, and B will be 
pooled with 2 mg/kg presented as a single dose group and 4, 5, 6, 7, 8, 9, 10 
mg/kg presented as separate dose groups; Part C1 dosing 4 mg/kg Q2W and 6 


 
 
 
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mg/kg Q2W will also be presented as separate dose groups. Data from planned, 
protocol-specified visits and unplanned visits will be included in listings, unless 
otherwise noted. Baseline tables will contain a total column when appropriate.   
10.1.1 Handling of Missing Data 
All data will be analyzed as they were collected in the database.  Missing data, other 
than as described in Section 0, will not be imputed. 
 
 


 
 
 
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10.1.2 Derived and Computed Variables 
The following derived and computed variables have been initially identified as 
important for pre-specified and exploratory analyses. Additional computed variables 
may be required to aid in analysis.  
Missing Date Components of AEs, Concomitant Medications (including Prior Cancer 
Treatments), and Medical History 
Every attempt will be made to obtain complete dates for any AEs, CMs, and Medical 
History; however, in the case of incomplete dates, the missing Day, Month or Year 
will be represented in listings as “UN”, “UNK” or “UNKN”, respectively.  Missing Hour 
or Minute in times will be represented as “UN”.   
Missing date components for AEs, CMs, and Medical History will not be imputed; 
however, AEs with incomplete start dates (and times, in the case of infusion-related 
reactions) will be attributed to treatment according to the following algorithm: 
x 
Only the year is reported: If the year is after or the same as the day of the 
first dose, the event will be considered treatment-emergent. 
x 
Only the month and year are reported: If the month is after or the same as 
the day of the first dose, event will be considered treatment-emergent. 
x 
Only the time is missing: If the event occurred on or after the day of the first 
dose in the treatment period, then the event will be considered treatment-
emergent. 
Dates with missing day values will be imputed to the 15th of the month when 
calculating time since the last prior cancer regimen or procedure. If a date is missing 
both day and month values, then the date will not be imputed and the prior cancer 
regimen or procedure will not be considered for selection as the last.  
Study Days Relative to First Infusion of Study Medication 
Study Day 1 is the day of the first infusion of CX-2009 (for subjects enrolled only to 
the main CTMX-M-2009-001 study) or the day of the first treatment with Zr-CX-2009 
(for subjects enrolled to the CTMX-M-2009-001 imaging substudy); negative Study 
Days occur prior to first infusion of study treatment; and positive Study Days are 
those after the first study treatment – e.g., Study Day -1 is the day immediately 
preceding the first study treatment, Study Day 2 is the day immediately following 
the first study treatment. 
Time on Study 
Time on study (months) is calculated as the study termination date minus the first 
infusion date (+1) – this value is divided by 30.4375 to obtain the time in months. 
If the study termination date is missing, the data cutoff date will be used.  
Time Since Prior Regimens or Procedures 
Time since prior regimens or procedures (weeks) is calculated as the first infusion 
date minus the end date of the last prior (relative to study) regimen or procedure 
(+1) – this value is divided by 7 to obtain the time in weeks. Regimen or procedure 
end dates will be imputed to the 15th of the month when only the month and year 
are reported. If only the year is reported, then end date will not be imputed and the 
regimen or procedure will not be eligible for selection as the last prior regimen or 
procedure.  
 
 


 
 
 
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Time Since Initial Histopathological Diagnosis 
Time since initial histopathological diagnosis (years) is calculated as the date of 
informed consent minus the date of the initial histopathological diagnosis (+1) – this 
value is divided by 365.25 to obtain the time in years.  
Time Since Most Recent Disease Recurrence/Progression 
Time since most recent disease recurrence/progression (years) is calculated as the 
date of informed consent minus the date of the most recent disease 
recurrence/progression (+1) – this value is divided by 365.25 to obtain the time in 
years.  
AEs with Missing Relationship 
Every attempt will be made to obtain complete information for AEs regarding 
relationship(s); however, in the case of missing data: 
x 
AEs with missing relationship designations will be considered “Related” to 
study treatment provided the AE onset date/time occurs on or after the initial 
dose of CX-2009 was initiated.  
Duration of Treatment 
Duration of treatment for CX-2009 will be derived by subtracting the start date of 
the first infusion from the stop date of the last infusion (+1)  - this value is divided 
by 30.4375 to obtain the time in months.  
Percent of Infusion 
The percent of each dose received will be calculated using the following formula 
rounded to one decimal place:  
Percent of Dose = Total Dose of Study Medication Administered  X 100 
               Total Planned Dose of Study Medication 
Duration of Infusion (min) 
Duration of infusion in minutes will be derived by subtracting the Infusion Start Time 
from the Infusion Stop Time. 
Laboratory Values with < or > Inequality Symbols 
Some continuous laboratory data include “<” or “>” symbols. Data will be presented 
in listings with their inequality symbol; however, for tabulation of summary statistics 
of safety laboratory results, the number associated with the inequality sign will be 
used for statistical calculations.  
Definition of Baseline 
Unless otherwise specified, a baseline measurement will be taken as the last non-
missing value prior to the start of study treatment. 
 
 


 
 
 
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11. SUBJECT CHARACTERISTICS AND DEMOGRAPHICS 
11.1 
Enrollment and Disposition of Subjects  
A summary table will include all subjects and present the total number of subjects 
consented, treated (including on treatment, off treatment, in follow-up, and off 
study), and in each analysis population.  In addition, the number and percentage of 
the study treatment termination reasons and the study discontinuation reasons will 
be presented.  The percentages will be based on the total number of subjects treated.   
Subjects who discontinued the study 30 or fewer days from the last dose of study 
drug are considered to have discontinued the study during the treatment period. 
Subjects who discontinue the study more than 30 days after the last dose of study 
drug are considered to have discontinued the study while in follow-up.  
11.2 
Protocol Deviations 
Protocol deviations will be listed for all subjects in the SP for whom deviations were 
reported. The listing will include the deviation classification (major or minor) as well 
as the deviation category. 
11.3 
Demographics and Baseline Characteristics 
Descriptive statistics will be generated for all demographic and baseline 
characteristics by dose level and cancer type in order to descriptively assess the 
comparability of the cohorts. The variables to be summarized are: 
Demographics - 
x 
Age at enrollment,  
x 
Date of Birth (listing only), 
x 
Sex,  
x 
Child-bearing potential,  
x 
Race and  
x 
Ethnicity  
Baseline subject characteristics –  
x 
Height (cm), 
x 
Weight (kg), 
x 
ECOG Performance Status, and 
x 
Cigarette smoking history: 
o 
Current versus former smokers,  
o 
Years since last use,  
o 
Number of packs per day, and  
o 
Years of tobacco use. 
x 
Subject cancer type and characterization:  
o 
Time since initial histopathological diagnosis (years),  
o 
Time since the most recent disease recurrent/progression (years),  
o 
Cancer type,  
o 
Stage at Study Entry, 
o 
CD166 Status at Baseline 
o 
Disease characterization (Locally Advanced unresectable, Metastatic),  


 
 
 
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o 
Whether or not the disease is measureable,  
x 
Subject prior cancer treatment:  
o 
Number of prior cancer treatment regimens per subject 
o 
Time since last prior cancer treatment end date (weeks) 
o 
Prior use of platinum-containing compounds (Yes/No) 
o 
Prior use of anti-PD-1/anti-PD-L1 treatment (Yes/No) 
o 
Prior use of any microtubule inhibitor (Yes/No) 
o 
Prior use of any platinum-containing compounds or microtubule inhibitor 
(Yes/No) 
o 
Prior radiotherapy (Yes/No) 
o 
Time since last prior cancer procedure (weeks) 
 
Categories for platinum-containing compounds, anti-PD-1/anti-PD-L1 treatment, 
microtubule inhibitors will be based on a search list provided by CytomX prior to the 
database lock.  
Other prior cancer treatment information including the regimen or procedure, 
treatment duration, best overall response, reason for therapy ended, and time since 
disease progression will be captured in a listing.  
12. Safety and Tolerability Analysis 
The primary objectives of the study is to evaluate the safety and tolerability of 
multiple doses of CX-2009, administered as monotherapy to subjects with advanced 
solid tumors and to determine the MTD and DLTs of CX-2009.   
Safety will be assessed on the basis of AEs, clinical laboratory data, vital signs, ECG 
parameters, and physical examinations. Dosing and exposure to CX-2009 will be 
presented. 
All safety data will be listed by subject within part and dose cohort in chronological 
order.  Summary tabulations of safety data will be performed as noted in the 
following sections. 
12.1 
Adverse Events and Serious Adverse Events 
Adverse events will be collected from start of treatment through the follow-up period. 
Serious adverse events occurring during the screening period will be collected on the 
Adverse Events form. All other AEs occurring during the screening period will be 
collected on the Medical History form.  
Adverse events will be coded in accordance with the Medical Dictionary for 
Regulatory Activities (MedDRA) Version 23.0. Adverse events will also be graded  by 
the National Cancer Institute - Common Terminology Criteria for Adverse Events 
(NCI-CTCAE) v4.03.   
Only treatment-emergent adverse events (TEAE) occurring and reported while on-
treatment and up to and including 30 days after the last dose of study drug will be 
included in the adverse event summaries. A treatment-emergent AE is an event that 
emerges during treatment (including on or after the day of Zr-CX-2009 treatment in 
subjects enrolled in the CTMX-M-2009-001 imaging substudy) having been absent 
pre-treatment, or worsens relative to the pre-treatment state. AEs occurring 
between informed consent and first dose as well as AEs occurring 31 or more days 
after last dose will be listed.  


 
 
 
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AE presentation will include incidence, grade (by NCI-CTCAE criteria), and 
relationship to study drug.   
An Investigator’s causality assessment is the determination of whether there exists 
a reasonable  possibility  that  the  study  drug  caused  or  contributed  to  an  
adverse  event.  The relationship to study drug will be categorized as “Related” or 
“Not Related.” Related AEs/SAEs are those judged by the Investigator to be 
definitely, probably, or possibly related or Unknown relationship to a study drug. 
TEAEs, including serious TEAEs, will be listed by subject within part and dose cohort 
in chronological order of AE start date/time.     
The verbatim term and MedDRA system organ class (SOC) and preferred term (PT) 
will be included in the listings along with start and end dates, time on study, severity, 
seriousness, relationship of the event to study drugs, action taken with the study 
drugs, other action taken, outcome, infusion reaction (IR) (Y/N), DLT (Y/N), and AE 
of special interest (AESI) (Y/N). 
The following listings will be provided: 
x 
TEAEs 
x 
TEAEs with CTCAE Grade 3 or Higher 
x 
TEAEs related to CX-2009 
x 
TEAEs related to CX-2009 with CTCAE Grade 3 or Higher  
x 
Infusion reactions 
x 
TEAEs leading to discontinuation of study drug 
x 
TEAEs leading to death 
x 
All SAEs 
x 
SAEs related to CX-2009 
x 
SAEs related to CX-2009 with CTCAE Grade 3 or higher 
x 
TEAE of Special Interest 
x 
DLT AEs 
x 
Deaths 
If there are no subjects who meet the criteria for any of these listings, the listing will 
be generated and will contain a statement, “No <criteria> were reported.” for 
example, if there are no deaths on study, the statement would be “No deaths were 
reported.”  
Overall AE summary tables will each be prepared by dose level, by cancer type, and 
by Breast Cancer cohort (TNBC, HR+/HER2-, HER2+), and will include the number 
and percentage of subjects with reports of: 
x 
TEAEs 
x 
TEAEs related to CX-2009 
x 
TEAEs with CTCAE Grade 3 or higher 
x 
TEAEs with CTCAE Grade 3 or higher related to CX-2009 
x 
TEAEs classified as infusion reactions 
x 
TEAEs classified as infusion reactions with CTCAE Grade 3 or higher 
x 
TEAEs leading to study drug discontinuation 
x 
TEAEs leading to study drug discontinuation and related to CX-2009 


 
 
 
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x 
Dose-Limiting Toxicities (DLTs) 
x 
Treatment-emergent SAEs (TESAEs) 
x 
TESAE related to CX-2009 
x 
TEAEs leading to death 
x 
TEAEs leading to death and related to CX-2009 
x 
TEAEs of Special Interest 
x 
TEAEs of Special Interest with CTCAE Grade 3 or higher 
x 
TEAEs of Ocular Toxicity related to CX-2009 
x 
TEAEs of Ocular Toxicity related to CX-2009 with CTCAE Grade 3 or higher 
x 
TEAEs of Neuropathy related to CX-2009 
x 
TEAEs of Neuropathy related to CX-2009 with CTCAE Grade 3 or higher 
x 
TEAEs of Hepatic Disorders related to CX-2009 
x 
TEAEs of Hepatic Disorders related to CX-2009 with CTCAE Grade 3 or higher 
This overall AE summary table will also be produced for the DSMB meetings. TEAEs 
categorized as Ocular Toxicity, Neuropathy, or Hepatic Disorders will be defined 
based on a search list provided by CytomX prior to database lock.  
Only TEAEs (excluding unrelated, fatal AEs with PT=”Malignant neoplasm 
progression”) will be included in the AE summaries and be tabulated by MedDRA SOC 
and PT within part and dose cohort.  Tables presenting summaries of frequencies 
and percentages of subjects reporting at least one TEAE within each MedDRA SOC 
and PT by dose level and by cancer type will be provided for TEAEs and TESAEs as 
follows: 
x 
All TEAEs  
x 
Grade 3 or higher TEAEs 
x 
TEAEs related to CX-2009 
x 
TEAEs related to CX-2009 by maximum severity grade 
x 
Grade 3 or higher TEAEs related to CX-2009 
x 
Grade 3 or higher TEAEs related to CX-2009 by maximum severity grade 
x 
TEAEs leading to study drug discontinuation 
x 
TEAEs leading to death 
x 
TEAEs leading to death related to CX-2009 
x 
TEAEs of Special Interest by maximum severity grade 
x 
TEAEs of Ocular Toxicity related to CX-2009 by maximum severity grade 
x 
TEAEs of Neuropathy related to CX-2009 by maximum severity grade 
x 
TEAEs of Hepatic Disorders related to CX-2009 by maximum severity grade 
x 
TESAEs 
x 
Grade 3 or higher TESAEs 
x 
Grade 3 or higher TESAEs related to CX-2009 
 
Each subject will be counted only once within each level of the summary (PT or SOC).  
If a subject experiences more than one TEAE within a PT or SOC, only the TEAE with 
the strongest relationship or the maximum severity, as appropriate, will be included 
in the summaries of relationship and severity.  


 
 
 
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The above list of summary tables will also be produced by MedDRA PT (based on 
descending frequency of the total column) by dose level or by cancer type.  
The TEAE summary tables by SOC and PT will be provided upon request to the DSMB. 
TEAE profile summaries will also be created for infusion reactions. This table will 
summarize the frequency of events, time from event onset to the start time of the 
first infusion (hours), time from the event onset to the start time of the most recent 
infusion (hours), duration of the event (hours), duration category (<1 hour, 1 to 6 
hours, >6 hours), severity grade, outcome, action taken, and other action taken with 
medication.  
Profile summaries will also be created for TEAEs of Ocular Toxicity, TEAEs of 
Neuropathy, and TEAEs of Hepatic Disorders. These tables will summarize the time 
from event onset to the start time of the first infusion (days), duration of the event 
(days), duration category (<=7 days, 7 to 14 days, >14 days), severity grade, 
outcome, action taken, and other action taken with medication.  
A tabular summary of deaths by study period (Screening, Treatment, Follow-Up) will 
be provided by dose level and by cancer type. 
No inferential statistical tests will be performed for safety analyses. 
12.2 
Study Drug Administration and Exposure   
Drug exposure will be summarized by CX-2009 Monotherapy dose level and by 
cancer type. The number of doses administered for CX-2009 will be summarized 
categorically and continuously. The duration of treatment (in weeks) will be 
summarized continuously as will the percent of dose of each study drug.   
The duration (weeks) will be calculated as (date of last dose of study drug - date of 
first dose of study drug + 1)/7.  
The number and percent of subjects who were administered a dose different from 
the planned total dose and the reason they received a dose different from the 
planned total dose will be summarized. Subjects may have more than one reason in 
this summary. 
A listing of exposure to the study drugs will be provided. 
12.3 
Concomitant Medications 
All medications taken within 30 days before the administration of study drug and all 
concomitant medications and therapies administered during the study will be 
recorded on the relevant eCRF.  Prior medications are defined as medications taken 
before the date of the first infusion.  Concomitant medications are defined as 
medications taken on or after the baseline visit during the study treatment period.  
If a medication is taken on the date of the first infusion and is continued after the 
Baseline visit, it will be considered as both a prior and concomitant medication. 
Medications will be coded using the World Health Organization Drug Dictionary 
(WHODrug) version dated March 2020 (B3). Concomitant medications will be 
tabulated.  Medication data will be summarized by Anatomic Therapeutic 
Classification (ATC) Level 4 within ATC Level 2 by dose level and by cancer type. 
Each subject will only be counted once within each level of the summary (ATC level 
2 or ATC level 4). 
 
 


 
 
 
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12.4 
Clinical Laboratory Tests 
The clinical laboratory tests collected on study are as follows:  
x 
Hematology:  Red Blood Cells, Hemoglobin, Hematocrit, Platelet, White Blood 
Cells, Absolute Neutrophils, Neutrophils, Absolute Lymphocyte, Lymphocyte, 
Absolute Monocyte, Monocyte, Absolute Basophils, Basophils, Absolute 
Eosinophils, Eosinophils, Blast Count, Reticulocyte count, MCV, MCH, MCHC 
x 
Blood chemistry: Albumin, Total Protein, Uric Acid, Sodium, Potassium, 
Chloride, Calcium, Calculated Creatinine Clearance, Phosphorus, Chloride, 
Bicarbonate, CO2, Blood Urea Nitrogen (BUN), Hemoglobin A1c, Urea, 
Creatinine, Lipase, Amylase, Magnesium, Glucose, Lactate Dehydrogenase 
(LDH), Serum ALT, Serum AST, Total Bilirubin, Alkaline Phosphatase. 
x 
Coagulation: Prothrombin time (PT) (sec), activated Partial Thromboplastin 
Time (aPTT) (sec), International Normalized Ratio (INR) 
x 
Urinalysis: 
o 
Blood, Protein, Glucose as negative, trace, positive, 0, +, ++, +++, 
>+++ (listings only) 
o 
Specific gravity, pH, Leukocytes, Ketones, Urobilinogen: Low, normal, 
high 
Select laboratory tests will be graded using the NCI-CTCAE version 4.03. The lab 
tests will be assigned Grades 1, 2, 3, or 4 if they meet the CTCAE criteria, regardless 
of designation of “Low” or “High” for the value. Grading will only be performed based 
on quantitative criteria (e.g. no clinical input required for grading). The following 
toxicities will be graded: aPTT prolonged, ALT increased, Hypoalbuminemia, ALP 
increased, AST increased, Blood bilirubin increased, Hypocalcemia, Hypercalcemia, 
Creatinine increased, Hypoglycemia, Hyperglycemia (fasting), Anemia, Hemoglobin 
increased, INR increased, Lymphocyte count decreased, Lymphocyte count 
increased, Hypomagnesemia, Hypermagnesemia, Neutrophil count decreased, 
Hypophosphatemia, 
Platelet 
count 
decreased, 
Hypokalemia, 
Hyperkalemia, 
Hyponatremia, Hypernatremia, White blood cell count decreased, Leukocytosis.  
Shift tables will be created separately for Hematology and Blood Chemistry 
parameters, by dose level and by cancer type.  The presentation in the table will be 
by CTCAE toxicity, and Grade 0 will be assigned for those values which are available 
and not assigned Grade 1, 2, 3 or 4. If the toxicity is bi-directional (e.g. Lymphocyte 
Count decreased, Lymphocyte count increased),  then for the high direction Grade 0 
will be assigned for the “low” direction. Similarly, for the low direction, Grade 0 will 
be assigned for the “high” direction. The shift tables will present shifts from baseline 
to worst post-baseline value. The worst post-baseline value could be any non-
missing value collected after the first infusion up to and including 30 days after the 
last infusion.  
Listings that include all laboratory results for any subject with any laboratory result 
outside of the normal range will be provided. 
12.5 
Other Safety Measures 
12.5.1 Vital Signs 
The mean change from baseline in vital signs will be presented in a figure for each 
vital sign parameter for both dose level and cancer type: Temperature (oC), Pulse 
rate (beats/min), Respiratory rate (breaths/min), Systolic Blood Pressure (mmHg), 
Diastolic Blood Pressure (mmHg), Pulse Oximetry (%) along with Weight (kg). 


 
 
 
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Separate lines will be presented by either dose level or cancer type as applicable in 
the figure.  
The figures will be presented by nominal time since treatment start (weeks), and 
only values obtained in protocol-specified windows will be summarized. If more than 
one value is obtained in a protocol-specified window, the value closest to the target 
day in the window will be used. If there is more than one value equidistant from the 
target within the window, the value occurring before the target day will be used.  
12.5.2 ECGs 
All ECGs will be 12-lead. ECG assessments, including QTcF intervals, will be listed in 
chronological order by subject for any subject with an abnormal (not clinically 
significant or clinically significant) overall result. 
13. Efficacy Analysis  
13.1.1 Primary Efficacy Endpoint 
The ORR is the primary efficacy endpoint. For solid tumors, response evaluation will 
be based on the RECIST criteria (v1.1) and ORR is defined as the proportion of 
subjects with complete response (CR) or partial response (PR) on two consecutive 
tumor assessments with scan dates at least 4 weeks apart according to RECIST 
(RECIST v1.1).  
The primary efficacy analysis will be based on the REP. Exact 2-sided 95% Cis (using 
the Clopper-Pearson method) will be calculated for all proportion estimates. 
A listing of tumor data including total tumor burden, RECIST v1.1 response 
assessments (target lesion evaluation, non-target lesion evaluation, and overall 
subject response) will be provided.  
Response Assessment and Best Overall Response – RECIST v1.1 
Efficacy outcomes will be summarized by dose level and by cancer type using RECIST 
v1.1 among the REP. The overall number of subjects for each dose; and the number, 
proportion, and 95% exact 2-sided CI (using the Clopper-Pearson method) of 
confirmed CR and PR, unconfirmed CR and PR, SD, PD, not evaluable (NE), overall 
response (CR + PR), disease control (CR + PR + SD) will be calculated. A summary 
table of the above response assessments by part using RECIST v1.1 among the REP 
will be provided. A swim lane plot of response assessment status over time using 
RECIST v1.1 will be produced.  
The best overall response is the best response recorded from the start of study 
treatment until the end of treatment taking into account any requirement for 
confirmation. If the best overall response is determined before the end of treatment 
(e.g., for an interim data cut), then it is the best response recorded from the start 
of study treatment until the date of the data cut.  
When no imaging/measurement is done at all at a particular time point, the subject 
is not evaluable (NE) at that time point. If only a subset of lesion measurements are 
made at an assessment, usually the case is also considered NE at that time point, 
unless a convincing argument can be made that the contribution of the individual 
missing lesion(s) would not change the assigned time point response (as may happen 
in the case of an assessment of PD).  
Complete or partial responses may be claimed only if the criteria for each are met at 
a subsequent time point as specified in the protocol (i.e., ~8 weeks later and no 


 
 
 
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earlier than 4 weeks later). In this circumstance, the best overall response can be 
interpreted as in Table 1.  
In the case of SD, measurements must have met the SD criteria at least once after 
study entry at a minimum interval of 7 weeks. If the first post-baseline response 
assessment is an SD and the assessment was less than 7 weeks from first dose of 
study drug, then the SD would be changed to NE. For the dose escalation parts of 
the study (i.e., parts A, A2), the reporting of CR/PR does not require confirmation as 
the primary objective is safety. Confirmation is required for the expansion cohorts 
(i.e., Part B).  
Table 1:  Best Overall Response Algorithm 
Overall Response 
First Time Point 
Overall Response 
Subsequent Time 
Point 
Best Overall Response 
CR 
CR 
CR 
CR 
PR 
SD, PD, or PRa 
CR 
SD 
SD provided minimum criteria for 
SD duration met, otherwise, PD 
CR 
PD 
SD provided minimum criteria for 
SD duration met, otherwise, PD 
CR 
NE 
SD provided minimum criteria for 
SD duration met, otherwise, NE 
PR 
CR 
PR 
PR 
PR 
PR 
PR 
SD 
SD 
PR 
PD 
SD provided minimum criteria for 
SD duration met, otherwise, PD 
PR 
NE 
SD provided minimum criteria for 
SD duration met, otherwise, NE 
NE 
NE 
NE 
CR = complete response, PR = partial response, SD = stable disease, PD = progressive disease, and NE 
= not evaluable. 
a If a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease 
meeting PR criteria relative to baseline makes the disease PD at that point (since disease must have 
reappeared after CR). Best response would depend on whether minimum duration for SD was met. 
However, sometimes ‘CR’ may be claimed when subsequent scans suggest small lesions were likely still 
present and in fact the subject had PR, not CR at the first time point. Under these circumstances, the 
original CR should be changed to PR and the best response is PR. 
Tumor burden assessed using RECIST v1.1 will be calculated as the sum of (the 
longest diameter of target non-nodal lesions plus the short axis of target nodal 
lesions).  The percent change from baseline will be plotted by time on study as a 
spider plot. The maximum percent change from baseline will be plotted in a waterfall 
plot.  The spider and waterfall plots will include all visits regardless of whether or not 
a response assessment has been recorded (as long as all baseline target lesions were 
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Additional efficacy figures may be provided by breast cancer subtypes (TNBC, 
HR+/HER2-, HER2+) as required.  
13.1.2 Secondary Efficacy Endpoints 
Secondary efficacy endpoints are:   
x 
DOR,  
x 
TTR,  
x 
PFS, and  
x 
OS. 
Time-to-Event Endpoints 
DOR 
DOR is defined as the time from the date of the first documentation of objective 
tumor response (i.e., ORR = CR or PR) that is subsequently confirmed to the date of 
the first documentation of objective disease progression or death due to any cause, 
whichever occurred first. DOR is only calculated for subjects in the REP who have a 
confirmed objective tumor response. Subjects who neither progress nor die will be 
censored on the date of their last tumor assessment. 
Table 2  Date of Censoring – DOR 
Description of 
Situation 
Date of Progression or Censoring 
Outcome 
No disease progression 
nor death on-study 
Date of last tumor assessment 
Censored 
TTR 
TTR is defined as the time from the date of the first dose of study drug to first 
documentation of confirmed objective tumor response. TTR is only calculated for 
subjects in the REP.  
PFS 
PFS is defined as the time from the date of the first dose of study drug to the date 
of first documentation of objective tumor progression (i.e., PD) or death due to any 
cause, whichever occurs first. Subjects who die without a reported progression will 
be considered to have progressed on the date of their death. Subjects who did not 
progress or die will be censored on the date of their last tumor assessment. Subjects 
who did not have any on-study tumor assessments and did not die will be censored 
on their date of first dose of study treatment. Subjects who started anti-cancer 
therapy without a prior reported progression will be censored on the date of their 
last tumor assessment prior to the initiation of subsequent anti-cancer therapy.  PFS 
is calculated for using the SP. 
Table 3.  Date of Progression or Censoring -- PFS 
Description of 
Situation 
Date of Progression or 
Censoring 
Outcome 
No baseline disease 
assessments 
Date of first dose of study 
drug 
Censored 


 
 
 
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Death before first 
disease assessment 
Date of death 
Progressed 
No disease progression 
nor death on-study 
Date of last tumor 
assessment with a response 
assessment other than not 
evaluable 
Censored 
Death without a 
reported progression 
Date of death 
Progressed 
No on-study tumor 
assessments and did 
not die 
Date of first dose of study 
drug 
Censored 
Subjects who started 
anti-cancer therapy 
without a prior reported 
progression 
Date of their last tumor 
assessment with a response 
assessment other than not 
evaluable prior to the 
initiation of subsequent anti-
cancer therapy 
Censored 
Died or progressed (on 
treatment*) after a 
missed assessment 
Date of death or disease 
progression 
Progressed 
Died or progressed in 
follow-up  
Date of last tumor 
assessment with a response 
assessment other than not 
evaluable  
Censored 
* Subjects who discontinued the study 30 or fewer days from the last dose of study 
drug are considered to have discontinued the study during the treatment period.  
Subjects who discontinue the study more than 30 days after the last dose of study 
drug are considered to have discontinued the study while in follow-up. 
OS 
OS is defined as the time from the date of the first dose of study drug to the date of 
death due to any cause (as captured on the Study Discontinuation, Treatment 
Termination, Substudy Discontinuation, Survival Status and/or AE CRF pages). Two 
analyses of OS will be conducted. The first will analyze all on-treatment deaths 
(deaths occurring within 30 days of last dose of study drug) while the second will 
analyze all on-study deaths (deaths occurring after first dose of study drug while on 
study).  Subjects who are last known to be alive and/or lost to follow-up are censored 
at the date of last contact (as captured on the Discontinuation Call, Study 
Discontinuation, Treatment Termination, Survival Status, and/or Substudy 
Discontinuation CRF pages).  Interim analyses of OS would use the data cut date as 
the censoring date of last contact if the subject is last known to be alive and/or lost 
to follow-up.  OS is calculated for using the SP. 
 
 


 
 
 
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Table 4.  Date of Censoring 
Description of Situation 
Date of Progression or 
Censoring 
Outcome 
Last known to be alive 
and/or lost to follow-up 
Date of last contact 
Censored 
Please note that the scan date of the tumor assessment associated with the 
reported response assessment will be used as the tumor response date 
referenced above (i.e., first documentation of objective tumor response, 
first 
documentation 
of 
objective 
disease 
progression, 
and 
first 
documentation of objective tumor progression). 
Estimates of time-to-event endpoints (DOR, TTR, PFS, and OS) will be obtained using 
the Kaplan-Meier method. Kaplan-Meier curves will be provided for these endpoints.  
A swim lane plot will be provided for DOR.  DOR and TTR will also be summarized 
using descriptive statistics for confirmed objective responders. 
The median, and 95% CIs around the DOR, TTR, PFS, and OS will also be calculated 
using the Kaplan-Meier method.  The range of TTR, PFS and OS will be provided as 
well.  Frequencies and percentages will be summarized for event rates and censored 
observations of the time-to-event endpoints.  Six- and twelve-month and 2-year 
survival rates will be included as well.  The number and percentage of disease 
progressions and deaths will be included (replacing the event rate) in the PFS 
summary.   
CBR16 and CBR24 
Breast cancer patients will also have CBR16 and CBR24 summarized by dose level 
and also by cancer subtype (TNBC, HR+/HER2-, HER2+). CBR16 is defined as the 
proportion of subjects with best overall response of CR or PR or with SD for at least 
16 weeks. CBR24 is defined as the proportion of subjects with best overall response 
of CR or PR or with SD for at least 24 weeks. CBR16 and CBR24 will only be calculated 
for subjects in the REP. 
SD Duration is defined as the time interval from the start of the treatment to the 
date of subsequent PD or on-treatment death. In the absence of PD or on-treatment 
death before the analysis cut-off date, it is the time from the start of treatment to 
the date of the last adequate tumor assessment before the cut-off date. 
13.1.3 Efficacy Measures during Follow-up 
Following the completion of study treatment, subjects with progressive disease will 
enter the follow-up period for monitoring of survival; subjects with SD, PR, or CR will 
enter the follow-up period for monitoring of DOR and PFS. Once a subject 
experiences progressive disease, they will continue to be monitored for survival. 
13.1.4 Eastern Cooperative Oncology Group (ECOG) Performance Status 
Eastern Cooperative Oncology Group (ECOG) performance status (0, 1, 2, 3, 4, and 
5) will be presented in a listing.  
 
 


 
 
 
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14. Pharmacokinetic, 
Immunogenicity, 
and 
Pharmacodynamic 
Assessments  
14.1 
PK Assessments 
A third-party PK vendor will conduct all analyses related to PK data.  Details of the 
PK analyses will be provided in a separate PK analysis plan. 
14.2 
Immunogenicity Assessments 
Serum samples will be collected from study participants, as described in the protocol 
to assess the immunogenicity of CX-2009. Samples will be initially screened for anti-
drug antibodies (ADA). If the sample is found to be ADA positive in the screening 
assay, a confirmatory assay and a titer assay will be performed to further 
characterize antidrug antibodies. 
Samples will be drawn at times indicated in the CTMX-M-2009-001 Protocol Module.  
Immunogenicity results will be listed by part and dose cohort. ADA statistical 
analyses will be detailed and summarized in a separate report.  
15. Exploratory Analyses 
15.1 
Pharmacodynamics and Exploratory Biomarkers 
The  overall  goal  of  the  biomarker  portion  of  CTMX-M-2009-001  is  to  explore  
x 
A)  Probody mechanistic  proof  of  concept,  and   
x 
B)  Potential predictive markers associated with CX-2009 clinical activity.  
This  information  will  help  to  further  build  the  translational  program  for  the  
development  of Exploratory studies will evaluate:   
x 
Probody activation in tumors compared to a peripheral normal tissue 
compartment (blood);  
x 
The potential link between markers, such as the target of CX-2009 (i.e., 
CD166), and mitotic markers (e.g., Ki-67), and the biological activity of CX-
2009; and  
x 
The presence of activated proteases in the human TME capable of removing 
the peptide mask and thereby activating the Probody-Tx. 
If the exploratory study results are presented in the CSR, a description of the 
methodology will be included there. 
15.2 
Additional Exploratory Analyses 
Upon review of the data, additional exploratory analyses may be conducted.  If these 
are presented in the CSR, a description of the methodology will be included there. 
 
 


 
 
 
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16. References 
International Conference on Harmonization (ICH) guideline “Statistical principles for 
Clinical trials”: E9, 1998.