An Open-Label, Dose-Finding and Proof of Concept Study of the PD-L1 Probody® Therapeutic , CX-072, as Monotherapy and in Combination With Yervoy (Ipilimumab) or With Zelboraf (Vemurafenib) in Subjects With Advanced or Recurrent Solid Tumors or Lymphomas
Phase: PHASE1
Conditions: Solid Tumor, Lymphoma
Sponsor: CytomX Therapeutics

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AN OPEN-LABEL, DOSE-FINDING AND PROOF OF CONCEPT STUDY 
OF THE PD-L1 PROBODYTM THERAPEUTIC, CX-072, AS 
MONOTHERAPY AND IN COMBINATION WITH YERVOY® 
(IPILIMUMAB) OR WITH ZELBORAF® (VEMURAFENIB) IN SUBJECTS 
WITH ADVANCED OR RECURRENT SOLID TUMORS OR 
LYMPHOMAS 
PROTOCOL MODULE NUMBER: CTMX-M-072-001 
(PROCLAIM-001: PROBODY CLINICAL ASSESSMENT IN MAN CX-072 
CLINICAL TRIAL 001) 
Product: 
CX-072
EudraCT Number: 
2016-002490-36 
IND Number: 
128042 
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 Director, Clinical Development 
CytomX Therapeutics, Inc. 
151 Oyster Point Boulevard 
Suite 400 
South San Francisco, CA 94080-1913 
Telephone: +1-650-825-5321 
Mobile: +1-415-680-8258 
Fax: +1-650-351-0353 
Date of Original Protocol Module: 
16 June 2016 
Date of Protocol Module 01: 
30 August 2016 
Date of Protocol Module 02: 
14 November 2016 
Date of Protocol Module 03: 
19 January 2017 
Date of Protocol Module 04: 
13 July 2017 
Date of Protocol Module 05: 
18 April 2018 
Date of Protocol Module 06: 
02 November 2018 

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Date of Protocol Module 07 
03 April 2020 (Not submitted) 
Date of Protocol Module 08 
04 June 2020 
Date of Protocol Module 09 
19 August 2020 
Confidentiality Statement 
This confidential information in this document is provided to you as an Investigator or consultant for 
review by you, your staff, and the applicable Institutional Review Board/Independent Ethics Committee. 
Your acceptance of this document constitutes agreement that you will not disclose the information 
contained herein to others without written authorization from the Sponsor. 

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1.
SIGNATURE PAGE
Title of Protocol Module: 
An Open-Label, Dose-Finding and Proof of Concept Study of the PD-L1 ProbodyTM 
Therapeutic1, CX-072, as Monotherapy and in Combination with Yervoy (Ipilimumab) or With 
Zelboraf (Vemurafenib) in Subjects with Advanced or Recurrent Solid Tumors or Lymphomas 
Protocol Module No: 
CTMX-M-072-001 
Protocol Module Version: 
Amendment 09 
Date of Module: 
19 August 2020 
1.1. 
Sponsor Approval 
____________________________________ 
_____________ 
 
Date 
Senior Vice President, Chief Medical Officer, CytomX Therapeutics, Inc. 
1.2. 
Investigator Agreement 
By signing this page, I attest that I have read and understand the contents of Common Core 
Document CTMX-C-001 (APPENDIX 1), Protocol Module CTMX-M-072-001, and any 
subsequent amendments to both documents. I agree to adhere to the design, conduct, and 
reporting requirements of the Protocol Module as stated in the Common Core Document and the 
CX-072 specific Protocol Module, CTMX-M-072-001, to my obligations to the Sponsor as
described in the Common Core Document and executed contracts between myself, my
Institution, and CytomX Therapeutics, Inc., the Sponsor.
Investigator's Signature: 
_____________________________________________ 
Investigator's Name:  
_____________________________________________ 
Institution: 
 
_____________________________________________ 
Date (dd/mmm/yyyy): 
_____________________________________________ 
1 “PROBODY, IHZ, and QZ are trademarks of CytomX Therapeutics, Inc. All other brands and trademarks 
referenced herein are the property of their respective owners.” 
DocuSign Envelope ID: 65FD3AE8-7201-4E77-B47C-8478DB92E820
20-Aug-2020 | 11:44 PDT

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2.
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF
FIGURES
TABLE OF CONTENTS 
1.
SIGNATURE PAGE ....................................................................................................3 
1.1. 
Sponsor Approval .........................................................................................................3 
1.2. 
Investigator Agreement ................................................................................................3 
2.
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES .................4 
3.
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS .............................12 
4.
INTRODUCTION ......................................................................................................16 
4.1. 
PD-1 and PD-L1 Inhibitors .........................................................................................16 
4.2. 
CX-072 Overview .......................................................................................................16 
 
 
 
 
 
 
4.4.2. 
Dose Escalation ..........................................................................................................20 
4.4.3. 
CX-072 Monotherapy Dose Effect .............................................................................21 
 
 
 
 
4.5. 
Rationale for Combination Therapy ...........................................................................23 
4.6. 
Study Rationale ...........................................................................................................26 
4.6.1. 
Study Rationale for Dose Escalation (Parts A Through C) ........................................26 
4.6.2. 
Study Rationale for Dose Expansion (Parts D and E) ................................................27 
5.
STUDY OBJECTIVES ..............................................................................................28 
5.1. 
Primary Objectives .....................................................................................................28 
5.1.1. 
Primary Objectives for Parts A Through C ................................................................28 
5.1.2. 
Primary Objective for Parts D 
 ..........................................................................28 
5.2. 
Secondary Objectives .................................................................................................28 
5.2.1. 
Secondary Objectives for Parts A Through C ............................................................28 
5.2.2. 
Secondary Objectives for Parts D 
 .....................................................................29 
 
 
 
 
 
 

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6.
OVERVIEW OF STUDY DESIGN ...........................................................................31 
6.1. 
Dose Limiting Toxicities and Late Stopping Rules ....................................................38 
6.1.1. 
Dose Limiting Toxicities ............................................................................................38 
6.1.2. 
Late Stopping Rules for Parts A Through C ...............................................................38 
6.1.3. 
Safety Review Committee for Dose Escalation Parts .................................................39 
6.2. 
Part A: Dose Escalation of CX-072 Monotherapy and Imaging Substudy ................39 
6.2.1. 
CX-072 Monotherapy Expansion for Imaging Substudy ...........................................41 
6.3. 
Part A2: CX-072 Monotherapy Dose Effect ..............................................................41 
6.4. 
Part B1: CX-072 Administered in a Concomitant Combination Schedule 
with Ipilimumab ..........................................................................................................42 
6.5. 
Part B2: CX-072 Administered in a Concomitant Combination Schedule 
with Ipilimumab ..........................................................................................................44 
6.6. 
Part C: Dose Escalation of CX-072 Plus Vemurafenib Combination ........................46 
6.7. 
Part D: Dose Expansion of CX-072 Monotherapy in Patients with Specific 
Tumor Types ...............................................................................................................47 
6.7.1. 
Undifferentiated Pleomorphic Sarcoma .....................................................................47 
6.7.2. 
Small Bowel Adenocarcinoma ...................................................................................48 
6.7.3. 
Cutaneous Squamous Cell Carcinoma ........................................................................48 
6.7.4. 
Merkel Cell Carcinoma ...............................................................................................49 
6.7.5. 
Thymic Epithelial Tumors ..........................................................................................50 
6.7.6. 
Anal Squamous Cell Carcinoma .................................................................................50 
6.7.7. 
Triple Negative Breast Cancer ....................................................................................51 
6.7.8. 
High Tumor Mutational Burden .................................................................................52 
6.8. 
 
 
7.
PATIENT ENROLLMENT ........................................................................................54 
8.
STATISTICAL CONSIDERATION ..........................................................................55 
8.1. 
Sample Size Determination ........................................................................................55 
8.1.1. 
Sample Size Determination for Parts A Through C ...................................................55 
8.1.2. 
Sample Size Determination for Parts D 
 ............................................................55 
8.2. 
Statistical Analyses .....................................................................................................57 
8.2.1. 
Statistical Analyses for Parts A Through C ................................................................58 
8.2.2. 
Statistical Analyses for Parts D
 ........................................................................58 
9.
DURATION OF TREATMENT AND FOLLOW-UP ..............................................61 

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9.1. 
Discontinuation of Patients from Treatment ...............................................................62 
9.2. 
Study Completion .......................................................................................................62 
10.
SELECTION OF PATIENTS .....................................................................................63 
10.1. 
Inclusion Criteria ........................................................................................................63 
10.1.1. 
Inclusion Criteria for Patients in Part A .....................................................................63 
10.1.2. 
Inclusion Criteria for Patients in Part A2 ...................................................................63 
10.1.3. 
Inclusion Criteria for Patients in Part B1 ....................................................................63 
10.1.4. 
Inclusion Criteria for Patients in Part B2 ....................................................................64 
10.1.5. 
Inclusion Criteria for Patients in Part C ......................................................................64 
10.1.6. 
Inclusion Criteria for Patients in Part D .....................................................................64 
10.1.7. 
 
10.1.8. 
Inclusion Criteria for All Patients in Parts A-  ..........................................................68 
10.2. 
Exclusion Criteria .......................................................................................................69 
11.
INVESTIGATIONAL PRODUCT ............................................................................71 
11.1. 
Identity of Investigational Product .............................................................................71 
11.2. 
Identity of Reference Therapy ....................................................................................71 
11.2.1. 
Yervoy (Ipilimumab) ..................................................................................................71 
11.2.2. 
Zelboraf (Vemurafenib) ............................................................................................71 
11.3. 
Packaging and Labeling of Clinical Supplies .............................................................71 
11.4. 
Storage of Clinical Supplies .......................................................................................71 
11.5. 
Dosage, Study Drug Preparation, and Administration ...............................................72 
11.5.1. 
CX-072 .......................................................................................................................72 
11.5.1.1. 
Product complaints .....................................................................................................73 
11.5.2. 
Yervoy (Ipilimumab) ..................................................................................................73 
11.5.3. 
Zelboraf (Vemurafenib) ..............................................................................................74 
11.6. 
Management of Infusion Reactions ............................................................................74 
12.
DOSE MODIFICATIONS OR MISSED DOSES .....................................................76 
12.1. 
Data Safety Monitoring Board ....................................................................................76 
12.1.1. 
Dose Modifications for CX-072 Adverse Events .......................................................76 
12.1.2. 
Special Instructions Regarding Dose Modification of Ipilimumab or 
Vemurafenib ...............................................................................................................79 
13.
PRIOR AND CONCOMITANT MEDICATIONS ....................................................80 

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14.
PHAMACOKINETIC, IMMUNOGENICITY, AND EXPLORATORY
BIOMARKER ASSESSMENTS ................................................................................81 
14.1. 
Pharmacokinetic Assessments ....................................................................................81 
14.1.1. 
Pharmacokinetics Collection ......................................................................................81 
14.2. 
Immunogenicity Assessments ....................................................................................81 
14.2.1. 
Immunogenicity Collection ........................................................................................81 
 
 
 
 
15.
STUDY PROCEDURES AND SCHEDULE OF EVENTS ......................................84 
16.
ADVERSE EVENTS ................................................................................................104 
16.1. 
Adverse Event Definitions ........................................................................................104 
16.1.1. 
Adverse Event ...........................................................................................................104 
16.1.2. 
Suspected Adverse Reaction .....................................................................................104 
16.1.3. 
Life-Threatening Adverse Event or Life-Threatening Suspected Adverse 
Reaction ....................................................................................................................104 
16.1.4. 
Serious Adverse Event or Serious Suspected Adverse Reaction ..............................104 
16.1.5. 
Unexpected Adverse Event or Unexpected Suspected Adverse Reaction ...............105 
16.2. 
Adverse Event Classification ....................................................................................105 
16.2.1. 
Relationship to Investigational Drug ........................................................................105 
16.2.2. 
Severity .....................................................................................................................105 
16.3. 
Exposure in Utero .....................................................................................................106 
16.4. 
Monitoring of Adverse Event Data ...........................................................................106 
16.5. 
Documentation of Adverse Events by Investigator ..................................................107 
16.6. 
Notification About Serious Adverse Events and Suspected Unexpected 
Serious Adverse Reactions .......................................................................................108 
16.6.1. 
Investigator Reporting to Sponsor ............................................................................108 
16.6.2. 
Serious Adverse Events Follow-Up ..........................................................................108 
16.6.3. 
Reporting to Regulatory Agencies and Institutional Review 
Board/Independent Ethics Committee ......................................................................109 
16.7. 
Rapid Notification of Events of Special Interest ......................................................109 
16.8. 
Module Specified Events ..........................................................................................110 
16.8.1. 
Module Specified Serious Adverse Events ...............................................................110 
16.8.2. 
Module Specified Adverse Events ............................................................................110 
16.9. 
Emergency Identification of Study Medication ........................................................112 

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17.
ETHICS ....................................................................................................................113 
17.1. 
Institutional Review Board or Independent Ethics Committee ................................113 
17.2. 
Ethical Conduct of the Study ....................................................................................113 
17.3. 
Patient Information and Informed Consent ..............................................................113 
18.
STUDY ADMINISTRATION .................................................................................114 
18.1. 
Common Core Document Amendments ...................................................................114 
18.2. 
Module Amendments ................................................................................................114 
19.
LONG-TERM EXTENSION INTRODUCTION ....................................................115 
19.1. 
Long-term Extension Rationale ................................................................................115 
20.
LONG-TERM EXTENSION OBJECTIVE .............................................................116 
20.1. 
Primary Objective .....................................................................................................116 
20.2. 
Long-term Extension Study Design ..........................................................................116 
21.
LONG-TERM EXTENSION STUDY ELIGIBILITY CRITERIA .........................117 
21.1. 
Inclusion Criteria ......................................................................................................117 
21.2. 
Exclusion Criteria .....................................................................................................117 
22.
LONG-TERM EXTENSION ENROLLMENT AND STUDY
PROCEDURES ........................................................................................................118 
22.1. 
Informed Consent .....................................................................................................118 
22.2. 
Enrollment ................................................................................................................118 
22.3. 
CX-072 Dispensation ................................................................................................118 
22.4. 
Safety Assessment ....................................................................................................118 
22.5. 
Tumor Imaging .........................................................................................................118 
22.6. 
Laboratory Assessments ...........................................................................................118 
22.7. 
End of Treatment ......................................................................................................119 
22.8. 
Follow-Up Phase ......................................................................................................121 
23.
LONG-TERM EXTENSION STUDY TREATMENT ............................................122 
23.1. 
Dose Interruption and Modification .........................................................................122 
23.2. 
Management of Infusion Reactions ..........................................................................122 
24.
DSMB MONITORING ............................................................................................123 
25.
LONG-TERM EXTENSION STUDY .....................................................................124 
25.1.1. 
Prior Therapy ............................................................................................................124 
25.1.2. 
Prohibited Medications .............................................................................................124 

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26.
LONG-TERM EXTENSION STUDY SAFETY MONITORING AND
REPORTING ............................................................................................................125 
26.1. 
Adverse Event Reporting for the Long-Term Extension ..........................................125 
27.
LONG-TERM EXTENSION STATISTICAL CONSIDERATIONS .....................126 
28.
REFERENCES .........................................................................................................127 
29.
APPENDICES ..........................................................................................................133 

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LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................12 
 
 
Table 3: 
Doses to be Tested 1 ....................................................................................................36 
Table 4: 
Dose Limiting Toxicity ...............................................................................................38 
Table 5: 
Part A Monotherapy: Dose Escalation Rules .............................................................41 
Table 6: 
3 + 3 Dose Escalation Rules .......................................................................................44 
 
 
 
Table 8: 
Assumptions and Criteria for Simon 2-Stage Design (Number Refers to 
Response Evaluable Patients) With 2.5% One-Sided Alpha and 95% Power ...........57 
 
 
Table 10: Management of Allergic Reactions ............................................................................75 
Table 11: Dose Modifications for CX-072 .................................................................................77 
Table 12: Schedule of Events: Parts A and D: CX-072 Monotherapy and Part C: 
CX-072 Plus Vemurafenib .........................................................................................85 
Table 13: Schedule of Events: Part A2: CX-072 Monotherapy .................................................89 
Table 14: Schedule of Events: Parts B1 and B2: CX-072 Plus Ipilimumab Combination .........93 
 
Table 16: Schedule of Events: Follow-Up Period for Parts A
of the Study .........................101 
Table 17: Pharmacokinetic Sampling Schedule .......................................................................102 
Table 18: Adverse Event Severity ............................................................................................106 
Table 19: Schedule of Events for Long-term Extension ...........................................................120 

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LIST OF FIGURES 
Figure 1: 
PD-L1 Probody Therapeutic .......................................................................................17 
 
 
 
 
Figure 3: 
Study Diagram ............................................................................................................32 
Figure 4: 
Phase 1/2a Dose Escalation, Dose Expansion, and Response Evaluation 
Schema ........................................................................................................................37 
Figure 5: 
Part A: Monotherapy CX-072 Dosing ........................................................................39 
Figure 6: 
Parts B1 and B2: Combination Dosing CX-072 Plus Ipilimumab .............................43 
Figure 7: 
Part C: Combination CX-072 Plus Vemurafenib Dosing ...........................................46 
Figure 8: 
Study Periods ..............................................................................................................61 
Figure 9: 
Long-Term Extension Study Schema .......................................................................116 

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3.
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
Table 1: 
Abbreviations and Specialist Terms 
Abbreviation or Specialist Term 
Explanation 
5-FU
5-fluorouracil
89Zr 
zirconium-89 
ADA 
anti-drug antibody(ies) 
AE 
adverse event 
AESI 
adverse event of special interest 
AIDS 
acquired immune deficiency syndrome 
ALT 
alanine aminotransferase 
ASCO 
American Society of Clinical Oncology 
AST 
aspartate aminotransferase 
AUC 
area under the plasma concentration-time curve 
BRAF 
B-Raf proto-oncogene, serine/threonine kinase
BRCA 
breast cancer gene 
bTMB 
tumor mutational burden in blood 
CAR 
chimeric antigen receptor 
CEA 
carcinoembryonic antigen 
CI 
confidence interval 
Cmax 
peak plasma concentration 
Cmin 
minimum plasma concentration 
CR 
complete response 
cSCC 
cutaneous squamous cell carcinoma 
CT 
computed tomography 
CTLA-4 
cytotoxic T-lymphocyte-associated antigen 4 
CYP 
cytochrome P450 
DLT 
dose limiting toxicity 
DOR 
duration of response 
DSMB 
Data Safety Monitoring Board 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EGFR 
epidermal growth factor receptor 

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Table 1: 
Abbreviations and Specialist Terms (Continued) 
Abbreviation or Specialist Term 
Explanation 
EOI 
end of infusion 
ER 
estrogen receptor 
ESMO 
European Society for Medical Oncology 
FDA 
Food and Drug Administration 
FIH 
first-in-human 
GI 
gastrointestinal 
GLP 
Good Laboratory Practices 
HCC 
hepatocellular carcinoma 
HER2 
human epidermal growth factor receptor 2 
HIV 
human immunodeficiency virus 
HNSTD 
highest non-severely toxic dose 
hTMB 
high tumor mutational burden 
ICF 
informed consent form 
IHC 
immunohistochemistry 
IP 
investigational product 
irAE 
immune-related adverse event 
IRB/IEC 
Institutional Review Board/Independent Ethics Committee 
IRF 
independent review facility 
IRR 
infusion-related reaction 
irRECIST 
immune-related Response Evaluation Criteria in Solid Tumors 
ITT 
Intent-to-Treat 
IV 
intravenous 
IWRS 
interactive web response system 
Kd 
elimination rate constant 
mAb 
monoclonal antibody(ies) 
MABEL 
minimum anticipated biological effect level 
MAD 
maximum achieved dose 
Mb 
megabase 
MCC 
Merkel cell carcinoma 
MCPyV 
Merkel cell polyomavirus 
MEK 
mitogen-activated protein kinase 

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Table 1: 
Abbreviations and Specialist Terms (Continued) 
Abbreviation or Specialist Term 
Explanation 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for 
Adverse Events 
NHP 
non-human primate 
NOAEL 
no-observable-adverse-effect level 
ORR 
objective response rate 
OS 
overall survival 
PET 
positron emission tomography 
PD 
pharmacodynamic(s) 
PD-1 
programmed cell death 1 
PD-L1 
programmed cell death ligand 1 
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 
PO 
oral 
popPK 
population pharmacokinetic 
PR 
partial response 
QSP 
quantitative systems pharmacology 
qXh 
every X hours 
qXwk 
every X weeks 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RO 
receptor occupancy 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SAR 
suspected adverse reaction 
SCC 
squamous cell carcinoma 
SD 
stable disease 
SOC 
standard of care 
SRC 
Safety Review Committee 
SUSAR 
suspected unexpected serious adverse reaction 

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Table 1: 
Abbreviations and Specialist Terms (Continued) 
Abbreviation or Specialist Term 
Explanation 
t1/2 
terminal half-life 
TET 
thymic epithelial tumor 
TMDD 
target mediated drug disposition 
TME 
tumor microenvironment 
TNBC 
triple negative breast cancer 
TPS 
tumor proportion score 
TTR 
time to response 
ULN 
upper limit of normal 
UPS 
undifferentiated pleomorphic sarcoma 
US 
United States 
USP 
United States Pharmacopeia 

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4.
INTRODUCTION
4.1. 
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 
cell death ligand 1 (PD-L1), a ligand that negatively regulates T-cell activity through its 
interaction with programmed cell 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 effectively restore the activity of tumor specific immunity, leading to responses in
approximately 60% of patients with advanced melanoma and approximately 20% of patients
across multiple additional tumor types (Herbst 2014; Lipson 2015). For example, nivolumab
(Opdivo®, Bristol-Myers Squibb Company) has been approved for the treatment of metastatic
squamous non-small cell lung cancer and classical Hodgkin Lymphoma; nivolumab and
pembrolizumab (Keytruda®, Merck Sharp and Dohme Corporation) have both been approved for
the treatment of advanced melanoma; atezolizumab (Tecentriq®, Genentech, Inc.), durvalumab
(Imfinzi®, AstraZeneca Pharmaceuticals LP), and avelumab (Bavencio®, EMD Serono, Inc.)
have been approved for locally advanced or metastatic urothelial carcinoma; cemiplimab-rwlc
(Libtayo®, Regeneron Pharmaceuticals, Inc.) has been approved for cutaneous squamous cell
carcinoma (cSCC); and avelumab has been approved for metastatic Merkel cell carcinoma
(MCC). These and other new agents will likely receive approval, as monotherapy and/or in
combination with other agents, for the treatment of other tumors as well.
4.2. 
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. Probody therapeutics are fully
recombinant monoclonal antibody (mAb) prodrugs designed to be preferentially activated by
proteases associated with the tumor microenvironment (TME). They differ from unmodified
mAb by the recombinant addition of a cleavable Prodomain comprised of a mask and
protease-cleavable substrate, which blocks the antibody. This mask is designed to block binding
to its target antigen until the Prodomain can be removed by tumor-associated protease cleavage
at the substrate and released in the presence of tumor-associated proteases. As such,
Probody therapeutics are administered in a form designed to bind their target in tumor tissue but
not in normal circulating cells or healthy tissues. In nonclinical models, Probody therapeutics,
including those targeting PD-L1, have been shown to reduce toxicity of the relevant unmasked
parent antibody while maintaining its antitumor activity. In patients, Probody therapeutics may
be particularly useful in clinical settings where target binding in healthy tissue limits patient
access to potent, efficacious regimens. CX-072 is designed to widen the therapeutic window by

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reducing interaction with PD-L1 in normal tissue environments while maintaining interaction 
with tumor tissue.  
CX-072 is a Probody therapeutic derived from a proprietary human anti–PD-L1 mAb. In patients
with various cancers, conventional anti–PD-L1 mAb (atezolizumab, avelumab, and durvalumab)
and anti–PD-1 mAb (nivolumab and pembrolizumab) have demonstrated clinical effectiveness as
monotherapy and/or in combination with other immunotherapies. However, significant
life-threatening toxicities have been observed with these agents, particularly in combination
regimens. The most common serious adverse events (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, such as ipilimumab
or vemurafenib.
Figure 1: 
PD-L1 Probody Therapeutic 
PD-L1 = programmed cell death ligand 1. 
Expression, purification, formulation, characterization, stability, and administration of CX-072 
are similar to that of other mAb. 
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 to activate
CX-072 because there is published evidence that they are associated with human tumors
(LeBeau 2013; Overall 2006), and generally, they have low activity in blood or in select normal
tissues.
A variety of in vitro, ex vivo, and in vivo experiments have been performed to demonstrate that 
Probody therapeutics are effectively activated by tumor-associated proteases. These experiments 
were performed with either CX-072 or other Probody therapeutics that are representative of what 
would be expected of CX-072 because their substrate sequences are similar. 
Data from these experiments have demonstrated that these Probody therapeutics are efficacious 
in multiple tumor models, including human cell line xenografts, patient-derived xenografts, 
mouse genetic models, and mouse syngeneic tumor models. These data demonstrate that 
Probody therapeutics are active under a wide variety of tumor conditions in vivo. In contrast, 

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Probody therapeutic activation and target binding in circulation and normal tissues is limited, as 
demonstrated by nonclinical ex vivo and in vivo models.  
CytomX developed a technique used to screen human tissues directly for the presence of 
protease activity ex vivo. Frozen human tissue samples were incubated with labeled Probody 
therapeutic, and cleavage and activation of the Probody therapeutic were detected either by 
binding of the Probody therapeutic to its target in the tissue sample (IHZ™ assay) or by assaying 
the Probody therapeutic directly for cleavage and removal of the mask using quantitative 
capillary electrophoresis (QZ™ assay). Utilizing the IHZ assay, CytomX analyzed 
approximately 200 human tumors taken from many different tumor types, and > 90% of samples 
had sufficient protease activity under these assay conditions to activate a Probody therapeutic 
that can be cleaved by proteases that also activate CX-072. This reflects the design of the 
Probody substrate to be cleavable by at least 1 of several different tumor-associated proteases. 
Accordingly, patient selection based on protease activity in tumors likely will not be necessary in 
the proposed studies, although CytomX intends to collect data on protease activity in patient 
samples. 
 
 
 
 
 
 
 
 
  
 
 
  
 
 

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4.4.2. 
Dose Escalation 
First, this study will evaluate the safety of CX-072 as monotherapy (Part A), and will initially 
enroll 1 patient per cohort, at doses of 0.03, 0.1, and 0.3 mg/kg, until ≥ Grade 2 treatment-related 
adverse events (AEs) are observed or the 1.0 mg/kg dosing cohort opens for enrollment, 
whichever comes first. Thereafter, an additional 2 patients will be enrolled at that dose level. All 
subsequent dose levels will enroll in the conventional 3 + 3 design. The maximum tolerated dose 
(MTD) is defined as the highest dose tested at which no more than 1 of 6 patients has 
experienced a dose limiting toxicity (DLT). This recommendation is based on the following:  
•
The safety of the approved PD-L1 inhibitor, atezolizumab, as well as other PD-L1
inhibitors in development have not shown acute toxicities in Phase 1 dose-escalation
studies;
•
Early signs of clinical activity were not demonstrated at doses below 1 mg/kg for agents
in this class (PD-1 and PD-L1 inhibitors, including BMS-936559 [PD-L1 inhibitor]
[Brahmer 2012], atezolizumab [Herbst 2014], MEDI4736, and avelumab [Powles 2014;
Segal 2015; Spigel 2015]).

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The initial exploration of monotherapy will use 1-patient cohorts in the first 3 dose levels to limit 
the number of cancer patients treated with sub-therapeutic doses. Once the initial assessment is 
complete in these patients and higher dose levels have passed the DLT dose assessment, 
intra-patient dose escalation will be permitted to potentially more therapeutic dose levels, but 
only for patients in these very first dose levels (0.03, 0.1, and 0.3 mg/kg). 
4.4.3. 
CX-072 Monotherapy Dose Effect
Once a given dose level in Part A has been cleared (e.g., the dose has been declared safe and 
enrollment into the next dose level has been initiated), 6 patients each with PD-L1+ cancer 
(at least 2 patients in each cohort with thymic epithelial tumor [TET]) will be enrolled into the 
CX-072 monotherapy dose effect part of the study (Part A2) at that dose.
The primary objective of Part A2 is to refine the selection of the MTD/maximum achieved dose 
(MAD) by exploring the relationship between dose/exposure versus the levels of activated 
CX-072 in the TME and in plasma in patients with PD-L1+ tumors. This analysis is an important
measure of CX-072 performance (which may vary by dose). The relationship between
dose/exposure versus safety and efficacy of CX-072 will also be evaluated in Part A2.
To generate additional PK and CX-072 cleavage data for dose selection, an additional 6 patients 
will be enrolled to each of 4 dose levels (0.3, 1, 3, and 10 mg/kg) in Part A2. Data from Part A2 
will help refine the selection of the MTD/MAD by measuring the amount of cleaved, activated 
CX-072 in the TME and in the periphery using paired tumor and blood samples (as a proxy for
healthy tissue in the periphery).
Data presented at American Society of Clinical Oncology (ASCO) 2017 reinforces that there is 
particularly high toxicity of PD-1/PD-L1 inhibitors in TET (Cho 2017; Giaccone 2017). 
Therefore, there is potential utility in gathering extra safety data at various doses in TET in the 
event that emerging clinical data support further evaluation in TET in the future.  
The focus of Part A2 is to obtain a gauge of the relationship between CX-072 dose/exposure and 
efficacy and PD markers in patients with PD-L1+ cancer. 
 
In Part A2, cohorts will be enrolled consecutively and, as such, each dosing cohort in Part A2 
must be filled before the next cohort can open. 
Patients must agree to participate in biomarker analysis and have a tumor site that is safe to 
biopsy. 

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4.5. 
Rationale for Combination Therapy 
Nonclinical mouse studies conducted by CytomX have demonstrated the ability of a surrogate 
PD-L1 Probody therapeutic to provide comparable anti-tumor activity to that of its parental 
antibody, at comparable doses, while minimizing induction of systemic autoimmunity in a 
diabetes susceptible non-obese diabetic mouse model. CytomX has also demonstrated reduced 
occupancy of the PD-L1 Probody therapeutic on peripheral blood T-cells in tumor-bearing mice, 
consistent with its ability to protect against autoimmunity. In non-GLP pilot toxicology studies in 
both cynomolgus monkeys and rats, CX-072 has been well tolerated. By localizing its activity to 

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the TME, CX-072 is expected to reduce systemic toxicities and expand clinical opportunities for 
targeting the PD-1/PD-L1 pathway in combination therapies. For example, replacing nivolumab 
with an anti–PD-L1 Probody therapeutic may not only improve the safety of the combination 
with ipilimumab, but may also increase efficacy by permitting full doses of both agents. 
Anti–PD-1/PD-L1 antibodies combined with the CTLA-4 inhibitor, Yervoy® (ipilimumab): 
efficacy gains at the expense of increased toxicity 
Despite the enormous potential of PD-1/PD-L1 blockade and other immunotherapies, they are 
not effective in all patients. Consequently, combination therapy has been sought as a means to 
improve efficacy. When nivolumab, an anti–PD-1 antibody, is added to ipilimumab, an 
anticytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody, in patients with advanced 
melanoma, both efficacy and toxicity increase. Fifty-eight percent of the patients achieve 
objective responses with the combination, compared to 19% and 41% for monotherapy 
ipilimumab and nivolumab, respectively (Larkin 2015), but 55% of the patients experience 
drug-related Grade 3 to 4 AEs compared to 16% and 27%, respectively. Presumably, as these 
agents are administered systemically and both the PD-L1 and CTLA-4 proteins are present on 
normal tissue, the synergy of effect between the 2 agents is not confined to the tumor and 
inflammation in normal tissues results in meaningful, sometimes life-threatening toxicity. 
One way to address the safety challenges with these combinations is by adjusting dose and 
schedule. However, to date this has proven insufficient to improve safety in a meaningful way. 
The combination of ipilimumab and nivolumab in advanced lung cancer, for example, is too 
toxic to be administered at full doses. When the doses are reduced by 1/3 and ipilimumab is 
administered less frequently (i.e., the “optimal” dose and schedule), approximately 30% of 
patients still experience treatment-related Grade 3 to 4 toxicities (Rizvi 2015). Most recently, 
Johnson reported 2 fatal cases of myocarditis with electrical instability and selective clonal 
T-cell infiltration in the myocardium and skeletal muscle (Johnson 2016). Therefore, new
approaches are needed to reduce serious toxicities that occur with potent immunotherapy
combinations, such as PD-1 pathway inhibitors combined with CTLA-4 inhibitors.
After the 1 mg/kg CX-072 monotherapy cohort in Part A has completed DLT evaluation and has 
been determined to be safe, as per protocol, evaluation of the safety of the combination of 
CX-072 with ipilimumab will be initiated in Part B1 and Part B2.
Part B1 of the study will evaluate a concomitant schedule of the combination of CX-072 and 
ipilimumab in patients with advanced solid tumors or lymphoma who have exhausted standard of 
care (SOC) therapies. Eligible patients cannot have had prior immunotherapy, including 
PD-1/PD-L1 and CTLA-4 inhibitors, but are excluded if there is any immunotherapy or 
PD-1/PD-L1 and CTLA-4 inhibitor therapy available for their specific disease in the country 
where they are being treated. Patients enrolled into Part B1 will receive escalating doses of 
CX-072 administered concomitantly with 3 mg/kg ipilimumab. If 10 mg/kg of CX-072 plus
3 mg/kg of ipilimumab is judged safe (as per protocol and confirmed by the Safety Review
Committee [SRC]), the dose of ipilimumab with 10 mg/kg of CX-072 will be escalated to
6 mg/kg ipilimumab. See Section 14.3 for details regarding biopsies associated with this cohort.
Part B2 of the study will also evaluate a concomitant schedule of the combination of CX-072 
and ipilimumab in patients with advanced solid tumors or lymphomas who have exhausted 
SOC therapies. However, unlike Part B1 where patients must be PD-1/PD-L1 inhibitor naive, 

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patients enrolled into Part B2 must have received a prior PD-1/PD-L1 inhibitor provided that the 
PD-1/PD-L1 inhibitor was discontinued for reasons other than toxicity.  
As patients in this part will most likely have progressed on or post PD-1/PD-L1 inhibitor 
treatment, the starting dose for Part B2 is 3 mg/kg CX-072 for the combination with 3 mg/kg 
ipilimumab, followed by escalation to 6 mg/kg. This way, lower doses of CX-072 will be spared 
from this patient population and increase the potential for clinical benefit. If no MTD for the 
combination with 3 mg/kg ipilimumab is established, the 10 mg/kg dose level of CX-072 will be 
evaluated in combination with 6 mg/kg ipilimumab. See Section 14.3 for details regarding 
biopsies associated with this cohort. 
Anti–PD-1/PD-L1 antibodies with the kinase inhibitor, vemurafenib 
Additional combinations of PD-1/PD-L1 inhibitors are also limited by significant toxicity. These 
include the combination of vemurafenib and the PD-L1 inhibitor, atezolizumab. Severe skin and 
neurological toxicities were reported in 2 patients with advanced melanoma who received a 
PD-1 inhibitor followed by vemurafenib (Johnson 2013). The toxicities were severe enough that 
vemurafenib treatment had to be discontinued in both cases.  
Updated clinical data from a study in patients with previously untreated melanoma explored 
concomitant administration of atezolizumab with vemurafenib were reported at the Society for 
Melanoma Research 2015 International Congress (Hamid 2015). Initially, 3 patients were treated 
in cohort 1 (20 mg/kg q3wk of atezolizumab and 720 mg twice daily of vemurafenib). Grade 3 
rashes and Grade 3 elevations in liver function tests were observed in the cohort. Two of the 
initial 3 patients responded, including 1 complete remission. To mitigate toxicity, the protocol 
was amended to initiate treatment with a run-in period with vemurafenib monotherapy twice 
daily for 56 days (n = 8) or 28 days (n = 6). Atezolizumab was then administered IV q3wk at 
20 or 15 mg/kg or 1200 mg in a fixed dose. The vemurafenib was given in a reduced dose of 
720 mg during the combination period. Seventeen patients were evaluable for response, with 
3 complete responses (CRs) and 10 partial responses (PRs) reported. Overall response rate was 
75% and 100% with 1 CR in each of the 56- and 28-day vemurafenib run-in cohorts, 
respectively. The run-in combination was shown to be well tolerated and there were no DLTs or 
treatment-related discontinuations of atezolizumab. Grade 3 AE rates for the concomitant 
regimen were higher (67%), than either of the 56- or 28-day regimens (38% and 33%, 
respectively). As the approved dose of vemurafenib was only tolerated in the single agent phase 
of the run-in but not in combination with atezolizumab, this dose escalation study evaluates the 
safety of the CX-072–vemurafenib combination at approved vemurafenib doses based on the 
anticipated tolerability of CX-072. 
After the 3 mg/kg CX-072 monotherapy cohort in Part A has completed DLT evaluation and has 
been determined to be safe, as per protocol, evaluation of the safety of the combination of 
CX-072 with vemurafenib will be initiated in Part C of the current study. In Part C, escalating
doses of CX-072, beginning at 1 mg/kg, will be administered to patients in combination with the
approved dose of vemurafenib 960 mg administered in oral (PO) form twice daily in patients
with B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutated, PD-1/PD-L1 and
BRAF-inhibitor naive, advanced or metastatic melanoma. The selected doses for the
combination will provide data on whether treatment with a targeted immunotherapy agent,
CX-072, can mitigate the toxicity previously seen when combining vemurafenib with a

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PD-L1 agent. There is no plan to add a mitogen-activated protein kinase (MEK) inhibitor to the 
vemurafenib/CX-072 combination at this time for the following reasons:  
•
Synergy between BRAF and PD-1 inhibitors has been demonstrated pre-clinically
(Cooper 2014);
•
Vemurafenib is approved as a single agent for the treatment of melanoma; and
•
There are mixed data regarding the immunosuppressive effect of MEK in combination
with vemurafenib/PD-L1.
Therefore, the safety of a 2-drug combination will be explored before adding a third agent. 
4.6. 
Study Rationale 
4.6.1. 
Study Rationale for Dose Escalation (Parts A Through C) 
This is an FIH, Phase 1/2a, open-label, multicenter, dose escalation, multidose study designed to 
evaluate the safety and tolerability as well as determine the MTD or MAD of CX-072 as 
monotherapy and in combination with ipilimumab or vemurafenib. As discussed in Section 4.4.2, 
the first part of the study (Part A) is a dose escalation of CX-072 monotherapy starting at 
0.03 mg/kg up to 30 mg/kg administered q2wk. The rationale for the starting dose of CX-072 
monotherapy is discussed in Section 4.4.1. The rationale for the dose frequency is discussed in 
Section 4.4.5. Part A2 is designed to help refine the selection of the MTD/MAD by measuring 
the amount of cleaved, activated CX-072 in the TME and in the periphery using paired tumor 
and blood samples (as a proxy for healthy tissue in the periphery).  
As discussed in Section 4.5, the combination of checkpoint inhibitors that block the PD-1 
pathway (e.g., nivolumab) with anti-CTLA-4 (e.g., ipilimumab), demonstrate synergistic effects 
in efficacy and toxicities which can be dose limiting. CX-072 is designed to be preferentially 
activated in the TME. It is hypothesized that CX-072 may not only improve the safety of the 
combination with ipilimumab but may also increase efficacy by permitting full doses of both 
agents. Part B1 of the study is designed to evaluate the safety, tolerability, and MTD/MAD of 
CX-072 when combined with ipilimumab in immunotherapy naive patients. Part B2 is also
designed to evaluate the safety, tolerability, and MTD/MAD of CX-072 when combined with
ipilimumab; however, unlike patients in Part B1, patients in Part B2 will have received a prior
PD-1/PD-L1 inhibitor (provided that the PD-1/PD-L1 inhibitor was discontinued for reasons
other than toxicity).
Similar to the combination of nivolumab with ipilimumab, additional combinations of 
PD-1/PD-L1 inhibitors are also limited by significant toxicity, including the combination of 
vemurafenib and the PD-L1 inhibitor, atezolizumab (discussed in Section 4.5). Part C is designed 
to evaluate the safety, tolerability, and MTD/MAD of CX-072 in combination with vemurafenib 
in advanced or metastatic melanoma patients with BRAF V600E mutations. Patients in Part C 
will be PD-1/PD-L1 and BRAF-inhibitor naive. The selected doses for the combination will 
provide data on whether treatment with a targeted immunotherapy agent, CX-072, can mitigate 
the toxicity previously seen when combining vemurafenib with a PD-L1 agent. 

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4.6.2. 
Study Rationale for Dose Expansion (Parts D and E) 
Enrollment in Parts A, A2, and B1 is complete and ongoing in Parts B2 and C. During dose 
escalation in Part A, the MTD was not reached; 46 patients in Parts A and A2 (including 
10 patients with TET) received at least 1 dose of CX-072 monotherapy. The most recent 
presentation of these data was at the annual meeting of the European Society for Medical 
Oncology (ESMO) on 22 October 2018. Safety data showed 5 cases (11%) of Grade 3/4 
CX-072-related AEs, 3 of which were immune-related: 1 case of pneumonitis in a patient with
TET post-radiotherapy, 1 case of thrombocytopenia/neutropenia in a patient with TET, and
1 case of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) increase in a subject
with estrogen receptor (ER) positive breast cancer and liver metastasis.
Of all patients treated with at least 1 dose of CX-072 monotherapy at ≥ 3 mg/kg and who had at 
least 1 post-baseline tumor assessment (n=18), 3 patients had an objective response: 1 patient 
with TET receiving 3 mg/kg CX-072 (unconfirmed), 1 patient with triple negative breast cancer 
(TNBC) with skin lesions receiving 10 mg/kg CX-072 (PR confirmed), and 1 patient with 
endometrial carcinoma receiving 10 mg/kg CX-072 (unconfirmed). Additionally, 11 patients 
(61%) experienced stable disease.  
Based on these encouraging findings, patients will be enrolled in Part D to further evaluate the 
safety, tolerability, and preliminary anti-tumor activity of CX-072 at 10 mg/kg.  
Part D will enroll patients with specific tumor types that have failed to respond or showed tumor 
progression despite SOC therapy, or are not candidates for SOC therapy, or are unwilling to 
undergo SOC therapy, or for whom no available therapy is expected to convey clinical benefit. 
The tumor types selected for Part D are based on patients with unmet medical need that have had 
preliminary responses in this clinical trial (e.g., TNBC with skin lesions) or other published 
clinical trials as discussed in Section 6.7. Tumor types include undifferentiated pleomorphic 
sarcoma (UPS), small bowel adenocarcinoma, cSCC, MCC, TET, anal squamous cell carcinoma 
(SCC), TNBC with skin lesions, and high tumor mutational burden (hTMB).  
 
 
  
 
 
 
 
 

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5.
STUDY OBJECTIVES
5.1. 
Primary Objectives 
5.1.1. 
Primary Objectives for Parts A Through C 
The primary objectives for Parts A through C of the study are: 
1. Evaluate the safety and tolerability of multiple doses of CX-072, administered as
monotherapy or in combination with ipilimumab or vemurafenib to patients with metastatic
or locally advanced unresectable solid tumors or lymphomas; and
2. Determine the MTD and DLTs of:
•
CX-072 as a monotherapy administered to PD-1/PD-L1 naive patients,
•
CX-072 in combination with ipilimumab administered to PD-1/PD-L1 and CTLA-4
inhibitor naive patients,
•
CX-072 in combination with ipilimumab administered to patients that have had prior
treatment with a PD-1/PD-L1 inhibitor, and
•
CX-072 in combination with vemurafenib administered to PD-1/PD-L1 naive patients.
5.1.2. 
Primary Objective for Parts D 
 
The primary objective of Parts D 
 of the study is to obtain preliminary and confirmatory 
evidence of the efficacy of CX-072 monotherapy, respectively, via the objective response rate 
(ORR) according to the Response Evaluation Criteria in Solid Tumors (RECIST v 1.1) (tumor 
types include: UPS, small bowel adenocarcinoma, cSCC, MCC, TET, anal SCC, TNBC with 
skin lesions, and hTMB [Part D only]), as assessed by Investigator (Part D) 
 
 
5.2. 
Secondary Objectives 
5.2.1. 
Secondary Objectives for Parts A Through C 
The secondary objectives for Parts A through C of the study are: 
1. Obtain preliminary evidence of anti-cancer activity on the basis of the following endpoints
in patients treated with CX-072 as monotherapy or when administered in combination with
ipilimumab or vemurafenib:
•
ORR by RECIST v 1.1
•
ORR by modified immune-related response criteria as defined in the Common Core
Document or Modified Cheson/Lugano Classification for Lymphomas
•
Time to response (TTR)
•
Duration of response (DOR)
•
Progression-free survival (PFS)
2. Characterize the incidence of ADA against CX-072 and ipilimumab

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3. Characterize the single and multidose PK profile of CX-072 when administered alone, and
CX-072, ipilimumab, and vemurafenib when administered in combination
4. Assess overall survival (OS) in patients receiving CX-072
5.2.2. 
Secondary Objectives for Parts D 
 
The secondary objectives for Parts D 
 of the study are: 
1. Further characterize the efficacy of CX-072 monotherapy as evidenced by:
•
DOR as assessed by Investigator (Part D) 
•
•
ORR by modified immune-related (ir) RECIST as defined in the Common Core
Document
•
PFS
2. Evaluate safety and tolerability of CX-072, administered as monotherapy
3. Characterize the incidence of ADAs against CX-072
4. Characterize the PK profile of CX-072
5. Assess OS in patients receiving CX-072
 
 
 
 
 

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6.
OVERVIEW OF STUDY DESIGN
This is an FIH, Phase 1/2a, open-label, multicenter, dose escalation, multidose study of CX-072. 
Approximately 60 study sites will be utilized. Parts A through C are designed to evaluate the 
safety and determine the MTD and/or MAD of CX-072 as monotherapy and in combination with 
ipilimumab or vemurafenib (see Figure 3). Parts D and E are designed to obtain preliminary and 
confirmatory evidence of anti-cancer activity, respectively. The doses to be tested in each part of 
the study and the dose escalation schema are outlined in Table 3 and Figure 4, respectively. Of 
note, this study will close without opening Part E. As of Amendment 09, Parts A-E are closed, 
and the long-term extension part of the study will begin (see Section 19). 
All patients in Part A2 (CX-072 monotherapy), patients in Part B2 receiving CX-072 + 3 mg/kg 
ipilimumab (but not patients receiving 6 mg/kg ipilimumab), TNBC with skin lesions cohorts in 
Parts D and E will undergo pre- and on-study treatment tumor biopsies to explore potential 
predictive markers associated with CX-072 clinical activity.  

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Figure 3: 
Study Diagram 
Note: In Part A, an expansion cohort of up to 22 additional patients is planned to be enrolled for an imaging substudy conducted 
in the Netherlands. 
1Patients discontinued prior PD-1/PD-L1 for reasons other than toxicity. 
IV = intravenous; PD-1 = programmed cell death; PD-L1 = programmed cell death ligand 1; PO = oral. 

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The study is divided into 7 parts: 
•
Part A: CX-072 monotherapy dose escalation and imaging substudy
o
Any metastatic or advanced unresectable solid tumor or lymphoma (n ≤ 33),
measurable or nonmeasurable disease
o
Immunotherapy naive, including PD-1/PD-L1 and CTLA-4 inhibitor therapy naive
(where there is no immunotherapy or PD-1/PD-L1 and CTLA-4 inhibitor therapy
available for their specific disease in the country where they are being treated)
o
CX-072 monotherapy (0.03, 0.1, 0.3, 1, 3, 10, and 30 mg/kg) IV every 14 days
(q2wk)
o
Expansion cohort of up to 22 additional patients (10 mg/kg CX-072 monotherapy) for
an imaging substudy conducted in the Netherlands
•
Part A2: CX-072 monotherapy dose effect
o
Any metastatic or advanced unresectable solid tumor or lymphoma (at least 2 patients
in each cohort with TET) (n ≤ 24), measurable disease, relapsed or refractory
o
Tumor proportion score (TPS) ≥ 1% membranous staining based on the
DAKO PD-L1 Immunohistochemistry (IHC) 22C3 pharmDx
o
Immunotherapy naive, including PD-1/PD-L1 and CTLA-4 inhibitor therapy naive
(where there is no immunotherapy or PD-1/PD-L1 and CTLA-4 inhibitor therapy
available for their specific disease in the country where they are being treated)
o
Participation in biomarker analysis and biopsies
o
CX-072 monotherapy (0.3, 1, 3, and 10 mg/kg) IV q2wk
o
Initiation of each cohort’s enrollment requires successful completion of the Part A
CX-072 monotherapy at that dose level
•
Part B1: CX-072 plus ipilimumab combination dose escalation (PD-1/PD-L1 inhibitor
naive)
o
Any metastatic or advanced unresectable solid tumor or lymphoma (excluding TET)
(n ≤ 30), measurable or nonmeasurable disease
o
Immunotherapy naive, including PD-1/PD-L1 and CTLA-4 inhibitor therapy naive
(where there is no immunotherapy or PD-1/PD-L1 and CTLA-4 inhibitor therapy
available for their specific disease in the country where they are being treated)
o
CX-072 (0.3, 1, 3, and 10 mg/kg) in combination with ipilimumab (3 or 6 mg/kg) IV
q3wk × 4 doses in a concomitant schedule followed by CX-072 monotherapy IV
q2wk
o
Initiation of cohort enrollment requires successful completion of the subsequent
CX-072 monotherapy dose level tested in Part A

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•
Part B2: CX-072 plus ipilimumab combination dose escalation (prior PD-1/PD-L1
inhibitor)
o
Any metastatic or advanced unresectable solid tumor or lymphoma (excluding TET)
(n ≤ 18), measurable disease
o
Prior therapy with PD-1/PD-L1 inhibitors, discontinued for reasons other than
toxicity
o
CTLA-4 inhibitor naive
o
CX-072 (3 and 10 mg/kg) in combination with ipilimumab (3 or 6 mg/kg) IV
q3wk × 4 doses in a concomitant schedule followed by CX-072 monotherapy IV
q2wk
o
Initiation of cohort enrollment requires successful completion of the subsequent
CX-072 monotherapy dose level tested in Part A
o
Participation in biomarker analysis and biopsies (only in cohorts receiving
CX-072 + 3 mg/kg ipilimumab [but not 6 mg/kg ipilimumab]) is mandatory
•
Part C: CX-072 plus vemurafenib combination dose escalation
o
BRAF V600E mutation-positive metastatic or advanced unresectable melanoma
(n ≤ 18), measurable or nonmeasurable disease
o
BRAF-inhibitor naive
o
Immunotherapy naive, including PD-1/PD-L1 and CTLA-4 inhibitor therapy naive
(where immunotherapy or PD-1/PD-L1 and CTLA-4 inhibitor therapy is not available
to the patient)
o
CX-072 (1, 3, and 10 mg/kg) IV q2wk in combination with vemurafenib 960 mg PO
twice daily (approximately every 12 hours [q12h]), concomitant schedule
o
Initiation of cohort enrollment requires successful completion of the subsequent
CX-072 monotherapy dose level tested in Part A
•
Part D: Expansion cohort for safety and efficacy at CX-072 10 mg/kg administered as
monotherapy
o
Patients with metastatic or locally advanced unresectable tumor types of UPS
(n ≤ 20), small bowel adenocarcinoma (n ≤ 25), cSCC (n ≤ 25), MCC (n ≤ 25), TET
(n ≤ 25), anal SCC (n ≤ 25), TNBC with skin lesions (n ≤ 25), and hTMB (n ≤ 25)
measurable disease, that have failed to respond or showed tumor progression despite
SOC therapy, are not candidates for SOC therapy, are unwilling to undergo SOC
therapy, or for whom no available therapy is expected to convey clinical benefit
o
Immunotherapy naive, including PD-1/PD-L1 and CTLA-4 inhibitor therapy naive
(where there is no immunotherapy or PD-1/PD-L1 and CTLA-4 inhibitor therapy
available to the patient)

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•

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Table 3: 
Doses to be Tested 1 
Dose 
CX-072
(mg/kg)
Cohort 
# 
Part A 
Dose 
Escalation 
CX-072
(mg/kg)
Monotherapy 
Cohort 
# 
Part A2 
Dose Effect 
CX-072
(mg/kg)
Monotherapy 
Cohort 
# 
Part B1 
CX-072 +
Ipilimumab
Combination
Cohort 
# 
Part B2 
CX-072 +
Ipilimumab
Combination
Cohort 
# 
Part C 
Dose Escalation 
CX-072 +
Vemurafenib 
Combination 
Part D 
Dose 
Expansion
Dose 
Ipilimumab 
Dose 
Ipilimumab 
Dose 
Vemurafenib PO 
q12h 
0.03 
1A 
0.03 
10 mg/kg 
0.1 
2A 
0.1 
0.3 
3A 
0.3 
3A2 
0.3 
3B1 
+ 3 mg/kg ipi
1 
4A 
1 
4A2 
1 
4B1 
+ 3 mg/kg ipi
4C 
+ 960 mg q12h vem
3 
5A 
3 
5A2 
3 
5B1 
+ 3 mg/kg ipi
5B2 
+ 3 mg/kg ipi
5C 
+ 960 mg q12h vem
10 
6A 
10 
6A2 
10 
6B1 
+ 3 mg/kg ipi
6B2 
+ 3 mg/kg ipi
6C 
+ 960 mg q12h vem
30 
7A 
30 
10 
7B1 
+ 6 mg/kg ipi
7B2 
+ 6 mg/kg ipi
1The Sponsor in consultation with the SRC may modify the doses of study drug in response to DLTs observed during the study. 

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Figure 4: 
Phase 1/2a Dose Escalation, Dose Expansion, and Response Evaluation Schema 
PD-1 = programmed cell death 1; PD-L1 = programmed cell death ligand 1; q2wk = every 2 weeks; SRC = Safety Review Committee. 

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6.1. 
Dose Limiting Toxicities and Late Stopping Rules 
6.1.1. 
Dose Limiting Toxicities 
All AEs will be captured according to the National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI CTCAE) v4.03 and considered DLTs as outlined by the criteria 
in Table 4. The DLT evaluation period is 28 days (Parts A, B1, B2, and C). 
Table 4: 
Dose Limiting Toxicity 
Suspected DLT Criteria 
DLT? 
Yes 
No 
Grade 5 AEs 
X 
Grade 4 AEs judged by the Investigator to be treatment-related or judged by the 
Sponsor as a DLT, regardless of Investigator-attribution* 
•
Any Grade 4 endocrinopathy.
X 
*Exceptions
The following Grade 4 hematologic AEs:
•
Grade 4 lymphopenia; and
•
Grade 4 neutropenia lasting ≤ 48 hours that is not associated with fever or
other clinically significant symptoms.
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: 
•
Any Grade 3 central nervous system event, regardless of duration or
reversibility.
X 
The following Grade 3 AEs will not be considered DLTs: 
•
Nausea, diarrhea, asthenia, constipation, pyrexia, and vomiting that
resolves within 48 hours with appropriate treatment;
•
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;
•
Clinically manageable endocrinopathy;
•
“Tumor flare” – defined as local pain, irritation, or rash localized at sites of
known or suspected tumor; and
•
AEs judged by the Investigator to be related only to vemurafenib without
contribution of CX-072.
X 
Grade 2 pneumonitis necessitating discontinuation of CX-072 is a DLT. 
X 
Grade 2 ocular toxicity necessitating discontinuation of CX-072 is a DLT. 
X 
AE = adverse event; DLT = dose limiting toxicity. 
6.1.2. 
Late Stopping Rules for Parts A Through C 
If ≥ 1 patient experiences ≥ Grade 4 CX-072–related AEs beyond the DLT evaluation period, 
further enrollment in that part of the study will not be permitted until a review by the SRC. In 
this situation, the SRC may recommend that further dosing in that part of the study be 
terminated; that further dosing may resume, but with added safety parameters; that dosing may 
continue, but only at lower doses; or that the regimen for drug administration be modified. 

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Implementation of these recommendations may result in a protocol amendment to ensure patient 
safety and, where required, can be implemented only after approval of an amended protocol. 
Implementation of these recommendations may require a substantial amendment in the 
participating EU Member States. 
6.1.3. 
Safety Review Committee for Dose Escalation Parts 
The SRC, comprised of at least 3 to 5 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 patient 
oversight will be made by the SRC. Details on the SRC are provided in APPENDIX 4. 
6.2. 
Part A: Dose Escalation of CX-072 Monotherapy and Imaging 
Substudy 
The primary objectives of Part A are to assess safety, tolerability, and determine the MTD and 
DLTs of CX-072 when administered as monotherapy. Up to 33 patients naive to immunotherapy, 
including PD-1/PD-L1 and CTLA-4 inhibitor therapy naive (where there is no immunotherapy or 
PD-1/PD-L1 and CTLA-4 inhibitor therapy available for their specific disease in the country 
where they are being treated) with any metastatic or advanced unresectable solid tumor or 
lymphoma who have failed SOC treatment may be enrolled in the dose escalation cohorts. 
Patients may have measurable or nonmeasurable disease.  
CX-072 monotherapy will be administered at the following doses: 0.03, 0.1, 0.3, 1, 3, 10, and
30 mg/kg.
The DLT period for CX-072 monotherapy determination is 28 days. Each cycle of CX-072 
monotherapy treatment is 8 weeks (see Figure 5). 
Patients enrolled at the first 3 dosing cohorts (0.03, 0.1, and 0.3 mg/kg) who complete the DLT 
assessment period may have their dose of CX-072 increased to a higher dose level provided that 
the relevant dose level has successfully passed the DLT period and the patient has not already 
progressed on study drug. 
Patients in the 0.03 mg/kg dosing cohort will be administered CX-072 by slow IV push over 
3 to 5 minutes q2wk. Beginning with the 0.1 mg/kg cohort, CX-072 will be administered IV over 
1 hour (0.1, 0.3, 1, 3, or 10 mg/kg) or ≥ 90 minutes (30 mg/kg) q2wk.  
Figure 5: 
Part A: Monotherapy CX-072 Dosing 
DLT = dose limiting toxicity; q2wk = every 2 weeks. 

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The first patient in each new dose escalation cohort will be dosed at least 1 day prior to any other 
patients in that cohort, to allow for observation of possible severe and/or serious acute 
(e.g., infusion-related) toxicities that might affect subsequent patient enrollment or dosing 
decisions. 
Enrollment into each of the first 3 cohorts will initiate with 1 patient until the first 3 dose levels 
are enrolled and treated successfully or 1 patient experiences a DLT or a ≥ Grade 2 study 
drug-related AE, whereupon an additional 2 patients will be enrolled at that dose level. All 
subsequent dose levels will enroll in the 3 + 3 design. If no patient in the first 3 cohorts 
experiences a DLT or ≥ Grade 2 study drug-related AE following the completion of the DLT 
assessment period for dose level 3, the study will switch to a 3 + 3 design.  
Enrollment into each subsequent cohort will be initiated with 3 patients. If none of the first 
3 evaluable patients in a cohort experiences a DLT, that dose level will be deemed safe and 
another 3 patients will be treated at the next higher dose level. If 1 of the first 3 patients 
experiences a DLT, 3 more patients will be treated at the same dose level. The SRC will consider 
AEs, particularly severe immune toxicities that may have occurred in patients in any cohort even 
beyond the DLT period, when making decisions/recommendations to proceed to the next higher 
dose level. 
The MTD is defined as the highest dose tested at which no more than 1 of 6 patients has 
experienced a DLT. When the MTD has been exceeded, a total of 6 patients must be enrolled in 
the previous dose tested and/or the stepdown dose to determine the MTD (see Table 5). 
Monotherapy dose escalation/DLT dosing period must be successfully completed in Part A at the 
Part A2 dose level before enrollment into Part A2 at that same dose level may be initiated. 
Monotherapy dose escalation/DLT dosing period must be completed in subsequent cohorts in 
Part A before enrollment in Parts B1, B2, or C may be initiated (i.e., 0.3 mg/kg CX-072 plus 
3 mg/kg of ipilimumab can only be enrolled after the 1 mg/kg monotherapy dose of CX-072 has 
been determined to be safe). 
Patients who discontinue study drug administration for reasons other than DLT may be replaced 
to ensure the minimum number of patients required for DLT evaluation is enrolled. Patients who 
have enrolled in the study and have withdrawn prior to receiving the first dose will be designated 
as screen failures. These patients, as well as those who withdraw prior to completion of the DLT 
period for reasons other than toxicity, may be replaced. 
Once monotherapy dose escalation is complete and the MTD or MAD has been determined for 
CX-072, monotherapy expansion may be initiated for an imaging substudy. The Part A
monotherapy imaging substudy will only be performed at up to 3 sites in the Netherlands and
will allow enrollment of up to 22 additional patients at a recommended dose of 10 mg/kg
CX-072. The imaging substudy will allow evaluation of the uptake of the tracer in the tumor
lesions and whole body distribution leading to new insights about Probody therapeutic binding
across lesions and patients and to relate these findings to subsequent treatment effects and
toxicity. Part D monotherapy expansion will enroll patients with UPS, small bowel
adenocarcinoma, cSCC, MCC, TET, anal SCC, TNBC with skin lesions, and hTMB and will be
initiated at a fixed dose of 10 mg/kg.

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In order for a given dose to be “completed,” the proportion of patients experiencing a DLT 
during monotherapy dose escalation may not exceed 33% with the rules outlined in Table 5. 
Table 5: 
Part A Monotherapy: Dose Escalation Rules 
# Patients 
in Cohort 
# DLTs/ 
# Patients 
Action 
1 
0/1 
Dose completed 
1 
1/1 
Add 2 additional patients to the cohort; all subsequent cohorts 3 + 3 design 
3 
0/3 
Dose completed 
3 
1/3 
Add 3 additional patients to the cohort 
3 
≥ 2/3 
Dose level is above the MTD, escalation ceases 
6 
1/6 
Monotherapy dose is completed 
6 
≥ 2/6 
Dose level is above the MTD, escalation ceases 
# = number; DLT = dose limiting toxicity; MTD = maximum tolerated dose. 
6.2.1. 
CX-072 Monotherapy Expansion for Imaging Substudy
Once monotherapy dose escalation is complete and the MTD or MAD has been determined for 
monotherapy CX-072, monotherapy expansion for imaging substudy may be initiated. The 
monotherapy expansion for imaging substudy will only be performed at up to 3 sites in the 
Netherlands and will allow enrollment of up to 22 additional patients at a recommended dose of 
10 mg/kg CX-072. The primary objective of this substudy is to evaluate the whole body 
distribution of zirconium-89 (89Zr)-CX-072 in patients with locally advanced or metastatic solid 
tumors or malignant lymphoma. Radiolabeling of CX-072 with the positron emission 
tomography (PET) radionuclide 89Zr enables serial non-invasive imaging and quantification of 
distribution of 89Zr-CX-072. By performing 89Zr-CX-072-PET scans prior to initiation of 
CX-072 treatment as part of the main study, whole body distribution and 89Zr-CX-072 can be
evaluated and compared to treatment response and toxicity during treatment.
For further details, refer to the CTMX-M-072-001 Substudy Protocol. The imaging substudy for 
this trial was closed to new patient enrollment in 2019. 
6.3. 
Part A2: CX-072 Monotherapy Dose Effect 
The primary objective of Part A2 is to obtain a gauge of the relationship between dose/exposure 
and PD, safety, and efficacy. Up to 24 patients will be enrolled at 4 dose levels with up to 
6 patients per cohort dose. In each cohort, at least 2 patients must have TET. Patients must be 
immunotherapy naive, including PD-1/PD-L1 and CTLA-4 inhibitor therapy naive (where there 
is no immunotherapy or PD-1/PD-L1 and CTLA-4 inhibitor therapy available for their specific 
disease in the country where they are being treated), and have a TPS ≥ 1% membranous staining 
based on the DAKO PD-L1 IHC 22C3 pharmDX. Patients must have measurable disease.  

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CX-072 monotherapy will be administered at the following doses: 0.3, 1, 3, and 10 mg/kg.
Patients will be administered CX-072 IV infused over 1 hour (0.3, 1, 3, and 10 mg/kg) q2wk. See 
Figure 5 for monotherapy CX-072 dosing.  
Each cohort’s enrollment into Part A2 may only be initiated after successful completion of the 
Part A CX-072 monotherapy at that same dose level. 
Six patients must be enrolled into each cohort before the next sequential cohort can be enrolled. 
All available safety data in Part A2 will be considered by the SRC.  
If at any time more than 1/3 of patients experiences a DLT, further enrollment will be halted 
until a review by the SRC. In this situation, the SRC may recommend that further dosing in that 
part of the study be terminated; that further dosing may resume, but with added safety 
parameters; that dosing may continue, but only at lower doses; or that the regimen for drug 
administration be modified. Implementation of these recommendations may result in a protocol 
amendment to ensure patient safety. 
Patients who have enrolled in the study and have withdrawn prior to receiving the first dose will 
be designated as screen failures and be replaced. 
Intra-patient dose escalation is permitted for patients enrolling in Cohorts 3A2 (0.1 mg/kg), 4A2 
(0.3 mg/kg), and 5A2 (3 mg/kg) with TET that have stable disease (SD) and have not 
experienced an immune-related AE (irAE). If a higher dose level has cleared the DLT period and 
the SRC judges the dose level as safe, intra-patient dose escalation will be permitted to higher 
dose levels, after consultation with the Medical Monitor, but only for patients in the first dose 
levels (0.3 mg/kg, 1 mg/kg, and 3 mg/kg). Patients may be allowed more than 1 dose escalation 
to reach the dose of 10 mg/kg. 
6.4. 
Part B1: CX-072 Administered in a Concomitant Combination 
Schedule with Ipilimumab 
The primary objectives of Part B1 are to assess the safety and tolerability and to determine the 
MTD and DLTs of CX-072 when administered in a concomitant combination schedule with 
ipilimumab. Up to 30 patients naive to immunotherapy, including PD-1/PD-L1 and CTLA-4 
inhibitor therapy naive (where there is no immunotherapy or PD-1/PD-L1 and CTLA-4 inhibitor 
therapy available for their specific disease in the country where they are being treated) with any 
metastatic or advanced unresectable solid tumor or lymphoma (excluding TET) who have failed 
SOC treatment may be enrolled. Patients may have measurable or nonmeasurable disease. 
Patients will be administered CX-072 IV infused over 1 hour (0.3, 1, 3, or 10 mg/kg), followed 
by ipilimumab (3 or 6 mg/kg) IV infused over 90 minutes q3wk for 4 doses. Following the 
completion of the combination treatment period, patients will continue to receive CX-072 q2wk.  
The DLT period for CX-072 plus ipilimumab combination therapy dose escalation is 28 days. 
Combination therapy will be administered for Cycle 1 and Cycle 2 (11 weeks of combination 
therapy). Cycle 1 of CX-072 plus ipilimumab combination treatment is 6 weeks, and Cycle 2 of 
CX-072 plus ipilimumab combination treatment is 5 weeks. Cycles of CX-072 monotherapy will
then commence, and each cycle of CX-072 monotherapy treatment is 8 weeks (see Figure 6).
A maximum of 4 doses of ipilimumab may be administered to any patient. 

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Figure 6: 
Parts B1 and B2: Combination Dosing CX-072 Plus Ipilimumab 
D/C = discontinue; DLT = dose limiting toxicity; qXwk = every X weeks. 
Enrollment into Part B1 may only be initiated after the subsequent monotherapy dose level in 
Part A has successfully passed the monotherapy DLT dosing period.  
The first patient in each new dose escalation cohort will be dosed at least 1 day prior to any other 
patients in that cohort, to allow for observation of possible severe and/or serious acute 
(e.g., infusion-related) toxicities that might affect subsequent patient enrollment or dosing 
decisions. 
Enrollment will be initiated in each cohort with 3 patients. If none of the first 3 evaluable 
patients in a cohort experiences a DLT, that dose level will be deemed safe and another 
3 patients will be treated at the next higher dose level. If 1 of the first 3 patients experiences a 
DLT, 3 more patients will be treated at the same dose level (see Section 6.1). The SRC will 
consider AEs, particularly severe immune toxicities that may have occurred in patients in any 
cohort even beyond the DLT period, when making decisions/recommendations to proceed to the 
next higher dose level. 
The MTD is defined as the highest dose tested at which no more than 1 of 6 patients has 
experienced a DLT. When the MTD has been exceeded, a total of 6 patients must be enrolled in 
the previous dose tested and/or stepdown dose to determine the MTD (see Table 6). 
Patients who discontinue study drug administration for reasons other than DLT may be replaced 
to ensure the minimum number of patients required for evaluation of the combination are 
enrolled. Patients who have enrolled in the study and have withdrawn prior to receiving the first 
dose of CX-072 will be designated as screen failures. These patients, as well as those who 
withdraw prior to completion of the DLT period for reasons other than toxicity, may be replaced. 

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In order for a given combination dose to be “completed,” the proportion of patients experiencing 
a DLT during monotherapy dose escalation may not exceed 33% with the rules outlined in 
Table 6. 
Table 6: 
3 + 3 Dose Escalation Rules 
# Patients 
in Cohort 
# DLTs/ 
# Patients 
Action 
3 
0/3 
Dose completed 
3 
1/3 
Add 3 additional patients to the cohort 
3 
≥ 2/3 
Dose level is above the MTD, escalation ceases 
6 
1/6 
Combination dose level is completed 
6 
≥ 2/6 
Dose level is above the MTD, escalation ceases 
# = number; DLT = dose limiting toxicity; MTD = maximum tolerated dose. 
The following conditions must be met before any patient can receive ipilimumab within a given 
combination cohort: 
•
The administration of the subsequent dose of CX-072 as monotherapy in Part A must
have successfully passed the DLT safety assessment period, prior to opening a new
cohort; and
•
The addition of ipilimumab to the regimen is clinically acceptable in the judgment of the
Investigator.
Determination of the monotherapy MTD will be a trial priority. As the eligibility criteria for 
Parts A and B1 are similar, patients will be preferentially enrolled into open slots for Part A. 
Part B1 will enroll patients when Part A does not have available slots or has been completed. 
6.5. 
Part B2: CX-072 Administered in a Concomitant Combination 
Schedule with Ipilimumab 
Prior to Amendment 6, patients enrolled and dosed in Part B2 received 4 doses of CX-072 
monotherapy during a run-in period followed by 4 doses of CX-072 in combination with 
ipilimumab; patients then continued to receive CX-072 monotherapy. Previously in Part B2, 
CX-072 was dosed as a monotherapy run-in for 8 weeks without showing any significant effect
prior to receiving their first dose of ipilimumab. As such, beginning with Amendment 6, the dose
schedule has been changed to concomitant administration of CX-072 and ipilimumab. The
primary objectives of Part B2 are to assess the safety and tolerability and to determine the MTD
and DLTs of CX-072 when administered in a concomitant combination schedule with
ipilimumab. Up to 18 patients naive to CTLA-4 inhibitors and with prior therapy with
PD-1/PD-L1 inhibitors, discontinued for reasons other than toxicity, with any metastatic or
advanced unresectable solid tumor or lymphoma (excluding TET) with measurable disease will
be enrolled. Patient biopsies are mandatory in cohorts receiving CX-072 + 3 mg/kg ipilimumab
(but not patients receiving 6 mg/kg ipilimumab).

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Patients will be administered CX-072 IV infused over 1 hour (3 or 10 mg/kg), followed by 
ipilimumab (3 or 6 mg/kg) IV infused over 90 minutes q3wk for 4 doses. Following the 
completion of the combination treatment period, patients will continue to receive CX-072 q2wk. 
The DLT period for CX-072 plus ipilimumab combination therapy dose escalation is 28 days. 
Combination therapy will be administered for Cycle 1 and Cycle 2 (11 weeks of combination 
therapy). Cycle 1 of CX-072 plus ipilimumab combination treatment is 6 weeks, and Cycle 2 of 
CX-072 plus ipilimumab combination treatment is 5 weeks. Cycles of CX-072 monotherapy will
then commence, and each cycle of CX-072 monotherapy treatment is 8 weeks (see Figure 6).
A maximum of 4 doses of ipilimumab may be administered to any patient in Part B2. 
The first patient in each new dose escalation cohort will be dosed at least 1 day prior to any other 
patients in that cohort, to allow for observation of possible severe and/or serious acute 
(e.g., infusion-related) toxicities that might affect subsequent patient enrollment or dosing 
decisions. 
Enrollment will be initiated in each cohort with 3 patients. If none of the first 3 evaluable 
patients in a cohort experiences a DLT, that dose level will be deemed safe and another 
3 patients will be treated at the next higher dose level. If 1 of the first 3 patients experiences a 
DLT, 3 more patients will be treated at the same dose level (see Section 6.1). The SRC will 
consider AEs, particularly severe immune toxicities that may have occurred in patients in any 
cohort even beyond the DLT period, when making decisions/recommendations to proceed to the 
next higher dose level. 
The MTD is defined as the highest dose tested at which no more than 1 of 6 patients has 
experienced a DLT. When the MTD has been exceeded, a total of 6 patients must be enrolled in 
the previous dose tested and/or stepdown dose to determine the MTD (see Table 6). 
Patients who discontinue study drug administration for reasons other than DLT may be replaced 
to ensure the minimum number of patients required for evaluation of the combination are 
enrolled. Patients who have enrolled in the study and have withdrawn prior to receiving the first 
dose of CX-072 will be designated as screen failures. These patients, as well as those who 
withdraw prior to completion of the DLT period for reasons other than toxicity, may be replaced. 
In order for a given combination dose to be “completed,” the proportion of patients experiencing 
a DLT during monotherapy dose escalation may not exceed 33% with the rules outlined in 
Table 6. 
The following conditions must be met before any patient can receive ipilimumab within a given 
combination cohort: 
•
The administration of the subsequent dose of CX-072 as monotherapy in Part A must
have successfully passed the DLT safety assessment period, prior to opening a new
cohort; and
•
The addition of ipilimumab to the regimen is clinically acceptable in the judgment of the
Investigator.

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6.6. 
Part C: Dose Escalation of CX-072 Plus Vemurafenib Combination 
Part C will enroll up to 18 patients naive to BRAF-inhibitors and naive to immunotherapy, 
including PD-1/PD-L1 and CTLA-4 inhibitor therapy naive (where immunotherapy or 
PD-1/PD-L1 and CTLA-4 inhibitor therapy is not available to the patient) with measurable or 
nonmeasurable BRAF V600E mutation-positive metastatic or advanced unresectable melanoma. 
The primary objectives for Part C are to assess the safety, tolerability, and determine the MTD 
and DLTs of CX-072 in combination with vemurafenib. Patients will receive an IV infusion of 
CX-072 over 1 hour (1, 3, or 10 mg/kg) q2wk with oral vemurafenib 960 mg taken PO twice
daily (approximately q12h).
The DLT period for CX-072 plus vemurafenib combination therapy dose escalation is 28 days. 
Each cycle of CX-072 plus vemurafenib combination treatment is 8 weeks (see Figure 7). 
Enrollment into Part C may be initiated only after the subsequent CX-072 monotherapy cohort in 
Part A has been completed and deemed safe by the Sponsor in consultation with the SRC.  
Figure 7: 
Part C: Combination CX-072 Plus Vemurafenib Dosing 
DLT = dose limiting toxicity; q12h = every 12 hours; q2wk = every 2 weeks. 
The first patient in each new dose escalation cohort will be dosed at least 1 day prior to any other 
patients in that cohort, to allow for observation of possible severe and/or serious acute 
(e.g., infusion-related) toxicities that might affect subsequent patient enrollment or dosing 
decisions. 
Enrollment will be initiated in each cohort with 3 patients. If none of the first 3 evaluable 
patients in a cohort experiences a DLT, that dose level will be deemed safe and another 
3 patients will be treated at the next higher dose level. If 1 of the first 3 patients experiences a 
DLT, 3 more patients will be treated at the same dose level. The SRC will consider AEs, 
particularly severe immune toxicities that may have occurred in patients in any cohort even 
beyond the DLT period, when making decisions/recommendations to proceed to the next higher 
dose level. 
Each new cohort of 3 patients may be initiated only after the previous CX-072 plus vemurafenib 
DLT review period has been completed and deemed safe by the Sponsor in consultation with the 
SRC and provided that the subsequent dose of CX-072 monotherapy has also been deemed to be 
safe in Part A. 
The MTD is defined as the highest dose tested at which no more than 1 of 6 patients has 
experienced a DLT. When the MTD has been exceeded, a total of 6 patients must be enrolled in 
the previous dose tested and/or stepdown dose to determine the MTD (see Table 6). 
Patients who discontinue study drug administration, for reasons other than DLT, may be replaced 
to ensure the minimum number of patients required for evaluation of the combination is enrolled. 

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Patients who have enrolled in the study and have withdrawn prior to receiving the first dose will 
be designated as screen failures. These patients, as well as those who withdraw prior to 
completion of the DLT period for reasons other than toxicity, may be replaced. Patients that did 
not experience a DLT but were administered < 80% of the vemurafenib will be considered 
nonevaluable for DLT and may be replaced. 
6.7. 
Part D: Dose Expansion of CX-072 Monotherapy in Patients with 
Specific Tumor Types 
Following the completion of the monotherapy dose escalation, specific tumor types will be 
enrolled in dose expansion to have the opportunity to observe the efficacy and safety of CX-072 
in these specific populations.  
CX-072 monotherapy will be administered at doses of 10 mg/kg, determined in Part A, q2wk.
Each cycle of CX-072 monotherapy treatment is 8 weeks. See Figure 5 for monotherapy CX-072
dosing. As noted in Table 7, the first 14 evaluable patients (small bowel adenocarcinoma, cSCC,
MCC, TET, anal SCC, and TNBC with skin lesions) and 20 evaluable patients (UPS) will be
assessed for requisite antitumor activity prior to expansion.
The SRC will evaluate safety data from Part D and make recommendations regarding safety on 
an ongoing basis no less than monthly. For Part D, DLTs will not be formally assessed as in 
Parts A, A2, B1, B2, and C. When reviewing the safety data the SRC will pay particular attention 
to higher grade events and AESIs. 
6.7.1. 
Undifferentiated Pleomorphic Sarcoma 
UPS (previously referred to as malignant fibrous histiocytoma) is an aggressive sarcoma of the 
soft tissue or bone with an incidence of approximately 1 new case per 100,000 people per year. 
SOC for UPS is surgery and/or radiation. Patients with metastatic, inoperable, or advanced 
recurrent or persistent UPS have a poor prognosis, which is reflected by a median survival of 
12 months after development of distant metastases, irrespective of the systemic treatment chosen 
(Linch 2014). Thus, there is an unmet medical need for novel therapy. 
PD-L1 expression is potentially elevated in UPS, with prognostic significance. In one series 
(Pollack 2017), 16/20 patients with UPS expressed PD-L1 (2+ to 4+) in the TME using a 
noncommercial laboratory-based assay. High expression of genes that were related to both 
antigen presentation and T-cell mediated immunity (as characterized by nanostring) was a 
common finding in UPS. High PD-L1 expression was associated with higher grade disease and 
PD-1+ T-cell infiltrate. While detectable PD-L1 was noted in a variety of subsets of soft tissue 
sarcoma, UPS had higher levels of PD-L1 expression compared to the other types evaluated 
(p=0.001) and PD-1 expression compared to other sarcoma subtypes (p=0.05). 
Another series of soft tissue sarcomas analyzed by Kim 2013 included 11 UPS with PD-L1 
expression in 9/11 (82%) patients.  
The ORR of pembrolizumab in UPS is compelling with 4/10 patients achieving an objective 
response, including 1 complete remission (Burgess 2017).  
Furthermore, increased protease dysregulation has been demonstrated in soft tissue sarcoma, 
(Yang 2014) reinforcing the potential of the Probody therapeutic to be activated locally in the 
tumor. 

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6.7.2. 
Small Bowel Adenocarcinoma 
Malignancies involving the small intestine are rare. Small bowel adenocarcinoma accounts for 
approximately 10,470 new cases and 1450 patient deaths annually in the United States (US) 
(Siegel 2018). Although the small intestine represents approximately 75% of the length and over 
90% of the surface area of the alimentary tract, small bowel malignancies account for only 3% of 
all GI tract neoplasms and approximately 0.5% of all cancers in the US (Neugut 1998; 
Arparicio 2014; Siegel 2018). 
Adenocarcinomas represent from 25% to 40% of small bowel cancers and usually present 
between the ages of 50 to 70 years, with a slight male predominance (Arparicio 2014). The 
incidence of adenocarcinoma is highest in the duodenum and decreases progressively throughout 
the rest of the small intestine. In a large single-institution study, records from 217 patients with 
small bowel adenocarcinoma were reviewed and 52% of the tumors occurred in the duodenum 
(Dabaja 2004). 
Currently there is no approved first-line regimen for the treatment of advanced small bowel 
adenocarcinoma. Systemic chemotherapy has utilized a fluoropyrimidine plus platinum 
combination therapy based on treatment for metastatic colorectal cancer. However, the response 
to standard chemotherapy regimens has been mixed, with response rates ranging from 18% and 
8 months median survival with combination of 5-fluorouracil (5-FU), mitomycin C, and 
doxorubicin, to 50% with an OS of 15.5 months with a regimen of capecitabine combined with 
oxaliplatin (CAPOX) (Overman 2009; Xiang 2012). 
While there have not been any clinical trials using immunotherapy drugs specifically for small 
bowel adenocarcinoma, 2 separate studies on archived tumor samples from patients with small 
bowel adenocarcinomas showed high expression of PD-L1 in 53% to 83% of cases 
(Pedersen 2015; Thota 2017). This high expression of PD-L1 suggests a strong potential for 
PD-L1 inhibitor treatment in small bowel adenocarcinoma. 
6.7.3. 
Cutaneous Squamous Cell Carcinoma  
cSCC is the second most common human skin cancer, with an estimated annual incidence of 
186,157 to 419,843 cases in the US (Karia 2013). The vast majority of cSCC is readily treated 
with local excision and cure; however, locoregional or distant metastases develop in 1.9% to 
2.6% of cases (Brougham 2012). Because of its rarity, few therapeutic trials are available for 
patients with metastatic or locally advanced unresectable cSCC and no SOC has been 
established.  
Chemotherapeutic agents such as cisplatin, 5-FU, capecitabine, methotrexate, cetuximab, 
bleomycin, and doxorubicin have been utilized in patients with metastatic or locally advanced 
cSCC that cannot be managed with surgical excision or radiation therapy. Data demonstrating 
efficacy are limited (NCCN Guidelines 2017). 
Preliminary data from some small studies with antibodies or small molecules that target the 
epidermal growth factor receptor (EGFR) have demonstrated potential efficacy in patients with 
advanced cSCC, but similar to the conventional chemotherapeutic agents, it is not clear if these 
drugs improve outcomes in patients with distant metastatic cSCC. A Phase 2 study was 
conducted in 36 patients with cSCC treated with cetuximab, an anti-EGFR antibody, 
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had locoregional disease and 8% had systemic metastases. The ORR was 28% with 8 patients 
experiencing a PR and 2 experiencing a CR. Fifteen patients had SD for an overall disease 
control rate of 69%. Three patients underwent complete resection of their tumor following 
treatment with cetuximab. In another small study, 16 patients with cSCC not suitable for local 
therapy were treated with panitumumab (6 mg/kg q2wk) (Foote 2014). An ORR was observed in 
5 (31%) patients, including 3 (19%) patients with a PR, and 2 (12%) patients with a CR. In a 
small Phase 2 study, 40 patients with incurable cSCC were treated with gefitinib, an oral 
inhibitor of EGFR at a dose of 250 mg daily (William 2017). A modest ORR of 16% was 
observed (6 PR in 37 evaluable patients). An additional 13 (35%) patients had SD at 8 weeks. 
The median durations of response and PFS were 31.4 months (95% confidence interval [CI], 
3.91%-not applicable) and 3.8 months (95% CI, 2.2%-5.7%), respectively. 
Promising data from patients with head and neck SCC and melanoma have led to research into 
treating cSCC patients with immunotherapy, particularly with antibodies directed against PD-1 
or its ligand PD-L1. The most extensive data to date come from a prospective Phase 1 expansion 
cohort using the experimental anti–PD-1 antibody cemiplimab (REGN2810) 3 mg/kg IV q2wk 
for up to 48 weeks. This study included 26 patients, 10 with metastatic disease and 16 with 
unresectable, locally advanced, cSCC (Papadopoulos 2018). The updated overall ORR was 46%, 
with 2 CR (7.7%) and 10 PR (38.5%). The disease control rate was 69.2%. A Phase 2 study with 
82 patients with advanced cSCC (EMPOWER-CSCC) has just been completed and initial reports 
suggest a 46% ORR, similar to the Phase 1 study. In September 2018, cemiplimab-rwlc, a mAb 
that binds to PD-1, received FDA approval as the first and only treatment for metastatic or 
locally advanced cSCC. This suggests the potential for PD-L1 inhibitor treatment in cSCC. 
6.7.4. 
Merkel Cell Carcinoma 
MCC of the skin is a rare, aggressive cutaneous malignancy with an estimated 1600 cases per 
year in the US and predominantly affects elderly Caucasians (Albores-Saavedra 2010). MCC is 
lethal in 33% of cases and carries a worse prognosis than malignant melanoma (Hodgson 2005). 
Surgery and/or radiation therapy may be curative for patients with locoregional MCC without 
metastases. Systemic chemotherapy (e.g., platinum-based therapy) has demonstrated high 
response rates (approximately 60%) in patients with metastatic disease, but the DOR is short 
(3 to 6 months) (Tai 2000; Bhatia 2011).  
With the discovery of the association with Merkel cell polyomavirus (MCPyV) and expression 
of high levels of PD-L1 in MCC tumors (Lipson 2013), immunotherapy directed against the 
PD-1 pathway has been used as an appropriate alternative to systemic chemotherapy. In 
March 2017, avelumab, a mAb that binds to PD-L1, was the first drug to receive FDA approval 
for the treatment of MCC in adult and pediatric patients. In a Phase 2 clinical trial, 88 patients 
who had received prior chemotherapy were treated with avelumab (10 mg/kg q2wk) 
(Kaufman 2016). There were 28 objective responses (32%), including 8 CRs (9%). Responses 
appeared to be durable, and the PFS and OS at 6 months were 40% and 69%, respectively. An 
exposure-response relationship for efficacy was noted for avelumab in MCC suggesting a higher 
dose than avelumab 10 mg/kg q2wk may be more efficacious; however, this evaluation was 
based on limited data from a single-arm trial (FDA BLA 761049 2016). In September 2017, the 
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Two other immunotherapy agents that target the PD-1 pathway, pembrolizumab and nivolumab, 
have also shown evidence of activity in patients with metastatic MCC. In a Phase 2 study, 
26 patients who were systemic therapy-naive were treated with pembrolizumab (2 mg/kg q3wk) 
(Nghiem 2016), and objective responses were observed in 14 of 25 evaluable patients (56%), 
including 4 CRs and 10 PRs. With a median follow-up of 33 weeks, only 2 of 14 patients (14%) 
had relapsed, and the 6-month rate of PFS was 67%. Furthermore, responses were observed in 
patients with MCPyV-positive tumors (62%) as well as in patients whose tumors were virus 
negative (44%). A case report in a 42-year old Hispanic man documented a marked reduction in 
tumor burden on nivolumab (3mg/kg q2wk) after only 4 cycles of treatment 
(Mantripragada 2015). This suggests the potential for PD-L1 inhibitor treatment in MCC. 
6.7.5. 
Thymic Epithelial Tumors 
TET are rare epithelial neoplasms arising in anterior mediastinum either as thymoma or thymic 
carcinoma with an incidence of 0.13/100,000 persons per year in the US (Engels 2010). 
Thymomas are indolent with a tendency toward local recurrence rather than metastasis. Thymic 
carcinomas are typically invasive, with a higher risk of relapse and death (Ogawa 2002). There 
are no known risk factors. For thymomas, there is a strong association with myasthenia gravis 
and other paraneoplastic syndromes (Safieddine 2014).  
There are currently no FDA-approved drugs to treat TET and no randomized clinical trials that 
provide guidance for therapy in these patients. Surgical resection of the thymus is typically the 
SOC (NCCN Guidelines 2018; Gomez 2011). The stage of the tumor determines whether the 
patient receives post-operative radiation therapy with or without chemotherapy. The typical 
chemotherapy regimen for first-line treatment may include cyclophosphamide, doxorubicin, and 
cisplatin or cisplatin and etoposide for TET if chemotherapy is given on its own. If 
chemotherapy is given concurrently with radiation therapy, the preferred regimen is etoposide or 
carboplatin and paclitaxel. A wide range of agents have been used when disease progression 
occurs despite treatment with front-line options, including sunitinib, everolimus, etoposide, 
ifosfamide, pemetrexed, octreotide, 5-FU plus leucovorin, gemcitabine, and paclitaxel 
(NCCN Guidelines 2018). 
Recently it has been shown that 70% of thymomas and 23% of thymic carcinomas express 
PD-L1, suggesting therapy with anti–PD-1/PD-L1 drugs could be of potential benefit in patients 
with locally advanced, unresectable, or recurrent disease. Data from a small single-center 
Phase 2 trial has shown that 41 thymic carcinoma patients who had progressed after receiving at 
least 1 prior line of chemotherapy achieved a 22.5% overall response rate when treated with 
200 mg pembrolizumab q3wk up to 2 years (Giaccone 2018). The median DOR was 22.4 months 
(95% CI, 12.3%-34.7%), which is longer than patients who received the SOC therapy 
(i.e., sunitinib was 16.4 months). This suggests the potential for PD-L1 inhibitor treatment in 
TET. 
6.7.6. 
Anal Squamous Cell Carcinoma 
Anal SCC comprises 2.5% of all digestive system malignancies in the US; 8600 new cases are 
diagnosed annually (Siegel 2018). The incidence of anal cancer in the general population has 
increased over the last 30 years. From an etiologic standpoint, anal cancer is more similar to 
genital malignancies than it is to other GI tract cancers. Epidemiologic and clinical studies show 
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Primary treatment for patients with metastatic anal carcinoma is 5-FU with cisplatin, 
carboplatin/paclitaxel with or without radiation therapy, or FOLFOX with or without radiation 
therapy.  
Recently, results with 2 immune checkpoint inhibitors that target the PD-1 pathway, nivolumab 
and pembrolizumab, have been reported in advanced anal SCC. In a small, prospective, Phase 2 
trial conducted in patients with chemorefractory metastatic anal SCC, nivolumab was 
administered at a dose of 3 mg/kg IV q2wk (Morris 2017). Of the 37 patients, 9 (24%) patients 
had an objective response, 2 (5.4%) patients had a CR, 7 (19%) patients had a PR, and 
17 (46%) patients had SD as best response. Median PFS was 4.1 months, and median OS was 
11.5 months. Although the data were very limited (n = 13 patients), overexpression of PD-1 and 
PD-L1 seemed to correlate with responses.  
In the KEYNOTE-028 trial, 25 patients with PD-L1-positive anal cancer were administered 
pembrolizumab at a dose of 10 mg/kg q2wk for up to 2 years (Ott 2017). Among the 24 patients 
with SCC histology, there were 4 confirmed PRs (overall response rate 17%) and an additional 
10 (42%) patients had SD as the best response. This suggests the potential for PD-L1 inhibitor 
treatment in anal SCC. 
6.7.7. 
Triple Negative Breast Cancer 
TNBC lacks expression of the 3 most commonly evaluated biomarkers (ER, progesterone 
receptor, and human epidermal growth factor receptor 2 [HER2] protein). TNBC accounts for 
about 15% to 20% of breast cancers, tends to be more aggressive than other breast cancer types, 
and is more common in African-American women and women under 40 years old 
(Curigliano 2011; Gonzalez-Angulo 2011; Penault-Llorca 2012; Dietze 2015). 
Many of the general principles applicable to advanced breast cancer of other phenotypes apply to 
TNBC. The 2014 ESO-ESMO guideline recommends anthracycline and taxane-based 
chemotherapy as initial treatment for locally advanced, noninflammatory TNBC (Cardoso 2014). 
For TNBC patients who are breast cancer gene (BRCA) mutation carriers, response rates and 
PFS are superior with first-line platinum treatment, but platinum drugs have not been shown to 
be effective in non-BRCA patients. Treatment of TNBC with standard chemotherapy often 
results in a short-lived response and is associated with significant toxicities (Gucalp 2011). 
There are several drugs in clinical trials for the treatment of TNBC. Many are therapies that 
target specific mutations or signaling pathways (Jamdade 2015). Immunotherapy has been shown 
to be effective in solid tumors, especially in tumors that tend to be more immunogenic such as 
TNBC. Early studies with 2 drugs that inhibit PD-1/PD-L1, pembrolizumab and avelumab, have 
shown mixed results in patients with TNBC.  
Pembrolizumab was used to treat patients with TNBC in 2 studies, KEYNOTE-012 and 
KEYNOTE-086 (Nanda 2016; Adams, Loi 2017; Adams, Schmid 2017). In the KEYNOTE-012 
study, 32 TNBC patients positive for PD-L1 expression were treated with pembrolizumab 
10 mg/kg IV q2wk. There was an overall response rate of 18.5% in the evaluable patients, with a 
median TTR of 17.9 weeks (7.3 to 32.4) (Nanda 2016). In the KEYNOTE-086 study, there were 
2 cohorts of TNBC patients treated with 200 mg pembrolizumab IV q3wk. Cohort A enrolled 
170 TNBC patients with and without PD-L1 expression who received prior treatment. Cohort B 
enrolled 52 TNBC patients positive for PD-L1 expression who had not received any prior 
treatment. In this study, the response rate was 5% for patients who received prior treatment 

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(regardless of PD-L1 expression) compared to a 23% response in PD-L1 positive patients who 
were not previously treated (Adams, Loi 2017; Adams, Schmid 2017). 
In the JAVELIN solid tumor study, 58 patients with TNBC were treated with 10 mg/kg 
avelumab IV q2wk (Dirix 2018). The confirmed overall response rate was 5.2% with a higher 
response seen in patients who were PD-L1 positive. 
For TNBC with skin lesions patients who have failed all SOC treatments, PD-L1 inhibitor 
treatment may have the potential to achieve response and clinical benefit in this difficult to treat 
population. Of note, in Part A, a 39-year-old female with TNBC was enrolled in the 10 mg/kg 
CX-072 q2wk cohort. At baseline, the patient’s target lesions included 2 lymph nodes and a
subcutaneous axillary nodule. On CX-072, the skin lesions resolved and the patient achieved a
sustained PR in visceral lesions.
6.7.8. 
High Tumor Mutational Burden 
Recently, data have been published showing a relationship between patients with hTMB and 
response to therapy with checkpoint inhibitors such as atezolizumab, nivolumab, and ipilimumab 
(Snyder 2014; Rosenberg 2016; Riaz 2017). In addition, tumor mutation load is associated with 
production of neoantigens, which may be recognized by the immune system, thereby enhancing 
a response to immune checkpoint inhibitors (Snyder 2014). 
In a Phase 2 study, 310 patients with urothelial carcinoma who progressed following treatment 
with platinum-based therapy were treated with 1200 mg atezolizumab IV q3wk. Of the 
310 patients, mutation load was estimated in 150 patients using tumor tissue collected during 
screening. There was a significantly higher median mutational load in patients who responded to 
treatment (12.4/ megabase [Mb]) compared to non-responders (6.4/Mb) (p<0.0001) 
(Rosenberg 2016). 
Similarly, in melanoma patients treated with ipilimumab, there was a significant difference in 
mutational load between melanoma patients who received clinical benefit compared to those who 
received little to no clinical benefit (p=0.01) (Snyder 2014). 
Recently, an assay to define tumor mutational burden in blood (bTMB) was validated using 
plasma samples from 2 different studies (POPLAR and OAK) in non-small cell lung cancer 
patients receiving the anti–PD-L1 agent, atezolizumab (Gandara 2017). The association between 
bTMB and atezolizumab efficacy was analyzed and the cut-point of ≥ 16 mutations/Mb was 
selected using samples from patients in the POPLAR study and validated using data from the 
OAK study. The results showed that bTMB ≥ 16 was associated with improved PFS and OS 
among patients treated with atezolizumab. 
These data support the potential for PD-L1 inhibitor treatment in patients who have an hTMB. 
 
 
 
 
 
 

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7.
PATIENT ENROLLMENT
Patients will be enrolled using an interactive web response system (IWRS). The investigative site 
will log into the IWRS to enroll a patient that meets eligibility for a part of the study. When 
multiple cohorts are open for enrollment, priority of enrollment into cohorts will be based on 
evaluation and verification of enrollment criteria (Section 10.1 and Section 10.2) for the various 
arms as follows: 
•
Part A > Part B1.
•
Subjects eligible for Part B2 must be PD-L1 experienced and ineligible for Parts A,
A2, B1, C, and D.
•
Any subject with an advanced melanoma and known BRAF V600E mutation will be
enrolled in Part C.
As soon as the recommended Phase 2 dose has been confirmed in Part A, subjects meeting the 
enrollment criteria for Part D will be enrolled.  
Once assigned, numbers for any screening failures, nontreated, nonevaluable, or discontinued 
patients will not be re-used. 
Under Amendment 6, enrollment cannot exceed the number specified in Stage 1 of the 
envisioned Simon 2-stage design as noted in Table 8. Opening of Stage 2 in this study is planned 
following discussions with regulatory authorities and an issuance of a subsequent protocol 
amendment. 

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8.
STATISTICAL CONSIDERATION
8.1. 
Sample Size Determination 
8.1.1. 
Sample Size Determination for Parts A Through C 
Cohorts of 1, 3, or 6 patients may be treated at each dose level for Parts A, B1, B2, or C in the 
3 + 3 design. The ultimate number enrolled to each study Part will depend on the observed safety 
at each cohort, where enrollment of additional patients (up to 6) may be required, as per protocol, 
to further elucidate the safety profile at a given dose level. Additionally, escalation may be halted 
before the highest planned dosing cohort is enrolled, should the MTD be defined at a lower dose.  
Thus, the maximum number of patients enrolled to this study during dose escalation is as 
follows: 
•
In Part A, 15 to 33 patients may be enrolled (1 to 6 patients per cohort, up to 7 cohorts);
•
In Part A2, 24 patients may be enrolled (6 patients per cohort, up to 4 cohorts);
•
In Part B1, 15 to 30 patients may be enrolled (3 to 6 patients per cohort, up to 5 cohorts);
•
In Part B2, 9 to 18 patients may be enrolled (3 to 6 patients per cohort, up to 3 cohorts);
and
•
In Part C, 9 to 18 patients may be enrolled (3 to 6 patients per cohort, up to 3 cohorts).
For Part A, an expansion cohort of up to 22 additional patients is planned to be enrolled for an 
imaging substudy conducted in the Netherlands.  
 
 
 
 
 
 
 
 
 
8.1.2. 
Sample Size Determination for Parts D 
 
For the Part D expansion, potentially eligible patients will be those with: UPS, small bowel 
adenocarcinoma, cSCC, MCC, TET, anal SCC, TNBC with skin lesions, and hTMB for the 
purposes of providing preliminary assessment of response, as well as additional safety 
assessment at doses of 10 mg/kg. The expansion cohorts are enrolled in a gated fashion as 
explained below. The number of patients mentioned in the following discussion refers to treated 

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patients with measurable disease at baseline per RECIST v1.1. Response refers to confirmed 
objective response. 
A total of 20 patients will be evaluated for UPS and 14 patients will be evaluated for small bowel 
adenocarcinoma, cSCC, MCC, TET, anal SCC, TNBC with skin lesions, and hTMB. 
 
 
 
 
 Patients of hTMB 
will be enrolled into Part D only for a total of 25 patients. As hTMB cohort may consist of 
multiple tumor types and therefore has greater uncertainty in terms of treatment benefit, an 
exploration based on 25 patients is warranted before further development in this indication. 
 
 
 
 
 
 
 
 
 
 
 
 
 

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8.2. 
Statistical Analyses 
Fatal AEs due to disease progression not considered related to study drug will be excluded from 
AE summaries. 

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8.2.1. 
Statistical Analyses for Parts A Through C 
All 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 patients, the above analyses will be conducted if 
data warrant.  
Subgroup analyses will be conducted for TET patients. These will include, but not be limited to, 
listings of AEs and response assessment.  
8.2.2. 
Statistical Analyses for Parts D 
 
Data for Parts D 
 will be analyzed by tumor type. In addition, safety data will be pooled 
across tumor types. 
Descriptive summaries will be provided. For continuous measures, these will include mean, 
median, standard deviation, and range. For categorical measures, these will include counts and 
percentages. 
The Intent-to-Treat (ITT) Population will include all enrolled patients who receive any amount 
of study drug. The Safety Analysis Population will include all enrolled patients who receive any 
amount of study drug. The Response Evaluable Population includes all subjects in the ITT 
Population who have measurable disease at baseline per RECIST v1.1.  
The ITT Population will be used for analyses related to patient characteristics and disposition. 
The Safety Analysis Population will be used to summarize safety data including study drug 
exposure, laboratory data, and adverse events. 
The Response Evaluable Population will be used to summarize efficacy data including ORR, 
DOR, TTR, PFS, and OS. Sensitivity analyses on ORR will be conducted based on the ITT 
Population, and patients in the Response Evaluable Population with at least 1 post-baseline 
disease assessment. 
The discordance between the Investigator and IRF assessments on objective response will be 
summarized. 
Objective response will be summarized by count and percentage. In addition, a 95% CI based on 
the method of Koyama and Chen (Koyama 2008) will be provided. This method is appropriate 
because it is proposed for Simon’s 2-stage design, accounting for the inherent futility analysis.  
DOR is defined as the time from the first documentation of objective response that is 
subsequently confirmed to the first documentation of disease progression as assessed by an IRF 
or death due to any cause on study, whichever occurs first. DOR is only calculated for patients 
who have a confirmed objective response. Patients who neither progress nor die will be censored 
on the date of their last tumor assessment. Patients who start subsequent anti-cancer therapy prior 
to progression will be censored on the date of their last tumor assessment prior to the initiation of 
subsequent anti-cancer therapy.  

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TTR is defined as the time from the date of the first dose of study drug to the first documentation 
of objective response as determined by an IRF. TTR is only calculated for patients who have a 
confirmed objective tumor response. 
PFS is defined as the time from the date of the first dose of study drug to the date of the first 
documentation of disease progression as determined by an IRF or death due to any cause on 
study, whichever occurs first. Patients who die without disease progression will be considered to 
have progressed on the date of their death. Patients who did not progress or die will be censored 
on the date of their last tumor assessment. Patients who did not have any on-study tumor 
assessments and did not die will be censored on their date of enrollment. Patients who start 
subsequent anti-cancer therapy prior to disease 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 on study. 
Estimates of time-to-event endpoints (DOR, TTR, PFS, and OS) will be obtained using the 
Kaplan-Meier method. The median duration and its 95% CI based on Brookmeyer and Crowley 
method (Brookmeyer 1982) will be provided.  
A separate statistical analysis plan (SAP) will be generated for Part E and additional details will 
be specified within the SAP. In instances where the SAP might contradict the analyses specified 
in the Common Core Document, the SAP supersedes the Common Core Document. 
A retrospective central review will be conducted to confirm diagnosis for TET patients. Patients 
who are determined not to have TET by central review will be included in safety analyses but 
excluded from efficacy analyses for TET.  
The following analyses may be conducted by tumor type: frequency of AEs of special interest 
(AESIs), irAEs, use of immune modulating agents, and discontinuation rate of treatment. 
Furthermore, the correlation of angiopoietin 2 and response and durability of response may be 
explored for each tumor type. 
 

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Additional statistical assessments/methods for safety, efficacy, PK/PD, and immunogenicity are 
found in the Common Core Document. 

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9.
DURATION OF TREATMENT AND FOLLOW-UP
The study is divided into periods with associated evaluations and procedures that must be 
performed at specific time points (see Figure 8). The schedule of study procedures summarizes 
the frequency and timing of efficacy, safety, and other study measurements. Results of tumor 
assessments must be reviewed and documented before administering the next study treatment. 
A patient who is withdrawn from the study during a DLT assessment period before the 
completion of the assessment period for a reason other than DLT will be replaced.  
An individual patient’s participation in the study Parts A-E is approximately 2 years. Upon 
activation of Amendment 09, Investigators may elect to allow patients who continue to receive 
clinical benefit to continue to receive study drug if permitted by the Sponsor (see Section 19, 
Section 20, and Section 21).  
Figure 8: 
Study Periods  
iv = intravenous; po = oral; qXd = every X days; qXwk = every X weeks. 
Following the completion of study treatment, patients with progressive disease will enter the 
follow-up period for monitoring of survival; patients with SD, PR, or CR will enter the follow-up 
period for monitoring of DOR and PFS. Once a patient experiences a withdrawal criterion (as 
outlined in Section 9.1), they will continue to be monitored for survival.  
Once Protocol Amendment 09 is approved at a site, patients receiving study treatment will be 
eligible to roll over to the long-term extension part of the study (see Section 19 through 
Section 27). Patients who are no longer receiving study treatment but are in the follow-up period 
for Parts A-E will have concluded their participation in the study due to Sponsor termination. 
Follow-up for survival will no longer be performed.   

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9.1. 
Discontinuation of Patients from Treatment 
Patients MUST discontinue investigational product (IP) (and non-IP at the discretion of the 
Investigator) for any of the following reasons: 
•
The patient experiences progression of disease by either RECIST or irRECIST
guidelines; for a patient with a single observation of disease progression, the patient may
continue until the next scheduled radiological assessment. If continued progression
(>20% increase in target lesions, unequivocal progression in non-target lesions or new
lesion(s) assessed by the Principal Investigator as likely representing new site(s) of
malignant disease), the patient must be discontinued from the trial.
•
The patient is unwilling or unable to adhere to the protocol.
•
The patient withdraws consent or is lost to follow-up.
•
The patient experiences an intercurrent illness that prevents further administration of IP
and/or reference therapy.
•
The patient experiences a DLT or an AE related to study drug(s) which precludes further
administration of the study drug(s).
•
The patient experiences a prolonged treatment delay (as defined in Section 12).
•
The patient becomes pregnant, either prior to the first dose of study drug or at any time
during treatment.
•
In the Investigator’s judgment, the patient should discontinue treatment.
•
The Sponsor terminates the study.
9.2. 
Study Completion 
For Parts A-E, the study will be completed approximately 2 years from when the last patient is 
enrolled, or when the last patient has completed treatment and the initial safety follow-up visit. 
For this trial, the last patient was enrolled on 16 September 2019. 
Once Protocol Amendment 09 is approved at a site, patients receiving CX-072 study treatment 
will be eligible to roll over to the long-term extension part of the study, and Parts A-E of Study 
CTMX-M-072-001 will be considered to be terminated by the Sponsor for patients who are 
currently in the follow-up phase. 

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10.
SELECTION OF PATIENTS
Up to 123 patients may be enrolled into the dose escalation cohorts (Parts A through C) and 
195 patients into the expansion cohort (Part D), and 250 patients in Stage 1 of the envisioned 
Simon 2-stage design in Part E for a total of up to 568 patients (if every cohort is completely 
filled). The current amendment allows enrollment up to Stage 1 of Simon 2-stage design. In 
Part A, an expansion cohort of up to 22 additional patients is planned to be enrolled for an 
imaging substudy conducted in the Netherlands. 
After signing the informed consent form (ICF) patients will be evaluated for CTMX-M-072-001 
study eligibility during the Screening Period (no more than 30 days before study drug 
administration) according to the following inclusion/exclusion criteria.   
10.1. 
Inclusion Criteria 
Patients who fulfill the following criteria at screening will be eligible for admission into the 
study. All patients must have histologically confirmed diagnosis of metastatic or locally 
advanced unresectable tumors that progressed or are intolerant to standard therapy as defined 
below. 
10.1.1. 
Inclusion Criteria for Patients in Part A 
•
Part A: any metastatic or advanced unresectable solid tumor or lymphoma, measurable or
nonmeasurable disease allowed, no further SOC therapy available
o
Immunotherapy naive, including PD-1/PD-L1 and CTLA-4 inhibitor therapy naive
(where there is no immunotherapy or PD-1/PD-L1 and CTLA-4 inhibitor therapy
available for their specific disease in the country where they are being treated)
10.1.2. 
Inclusion Criteria for Patients in Part A2 
•
Part A2: any metastatic or advanced unresectable solid tumor or lymphoma (at least
2 patients in each cohort with TET), measurable disease allowed, no further SOC therapy
available
o
TPS ≥ 1% membranous staining based on the DAKO PD-L1 IHC 22C3 pharmDx
o
Immunotherapy naive, including PD-1/PD-L1 and CTLA-4 inhibitor therapy naive
(where there is no immunotherapy or PD-1/PD-L1 and CTLA-4 inhibitor therapy
available for their specific disease in the country where they are being treated)
o
Agreement to participate in biomarker analysis and have a tumor site that is safe to
biopsy
10.1.3. 
Inclusion Criteria for Patients in Part B1 
•
Part B1: any metastatic or advanced unresectable solid tumor or lymphoma (excluding
TET), measurable or nonmeasurable disease allowed, no further SOC therapy available
o
Immunotherapy naive, including PD-1/PD-L1 and CTLA-4 inhibitor therapy naive
(where there is no immunotherapy or PD-1/PD-L1 and CTLA-4 inhibitor therapy
available for their specific disease in the country where they are being treated)

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10.1.4. 
Inclusion Criteria for Patients in Part B2 
•
Part B2: any metastatic or advanced unresectable solid tumor or lymphoma (excluding
TET) with measurable disease allowed, no further SOC therapy available
o
Previous treatment with a PD-1/PD-L1 inhibitor
o
Discontinued treatment with PD-1/PD-L1 inhibitor for reasons other than toxicity
o
Naive to treatment with a CTLA-4 inhibitor
o
Agreement to participate in biomarker analysis and have a tumor site that is safe to
biopsy (only in cohorts receiving CX-072 + 3 mg/kg ipilimumab [but not 6 mg/kg
ipilimumab])
10.1.5. 
Inclusion Criteria for Patients in Part C 
•
Part C: metastatic or advanced unresectable melanoma with BRAF V600E
mutation-positive as detected by a diagnostic approved test (in the region where the
patient is treated), measurable or nonmeasurable disease allowed
o
Naive to treatment with BRAF-inhibitor
o
Immunotherapy naive, including PD-1/PD-L1 and CTLA-4 inhibitor therapy naive
(where immunotherapy or PD-1/PD-L1 and CTLA-4 inhibitor therapy is not available
to the patient)
10.1.6. 
Inclusion Criteria for Patients in Part D 
•
Part D: measurable disease is required.
−
Must be willing to provide a blood sample at screening for hTMB testing
−
Immunotherapy naive, including PD-1/PD-L1 and CTLA-4 inhibitor therapy
naive (where there is no available life-prolonging immunotherapy or PD-1/PD-L1
and CTLA-4 inhibitor therapy to the patient) of the following tumor types:
o
UPS
−
Metastatic or advanced unresectable UPS
−
TPS ≥ 1% membranous staining or unknown PD-L1 status
−
Patients must have had SOC surgery and/or radiation for their UPS; patients with
metastatic disease should have received at least 1 prior systemic therapy
according to local guidelines
o
Small bowel adenocarcinoma
−
Have metastatic or locally advanced unresectable small bowel adenocarcinoma of
the duodenum, jejunum, ileum (excluding neuroendocrine, ampullary, and
appendiceal tumors)

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−
Patients must have had at least 1and no more than 3 prior lines of systemic
chemotherapy for metastatic or advanced unresectable disease; adjuvant therapy
does not count as first-line therapy unless cancer recurs < 6 months after last
administration of that regimen
o
cSCC
−
Has metastatic or locally advanced unresectable primary cSCC;
o
MCC
−
Metastatic or advanced unresectable MCC
−
Prior surgical resection was performed if resectable or potentially of benefit
−
Radiation therapy administered if of potential benefit with documented
progression following completion of radiation therapy
o
TET
−
Histologically confirmed diagnosis of TET (classified in accordance with 2015
World Health Organization criteria) with stage II, III, or IV disease per
Masaoka-Koga 1994; details provided in APPENDIX 2
−
Received at least 1 prior chemotherapy regimen
o
Anal SCC
−
Metastatic or locally advanced unresectable anal SCC
−
Must have had prior radiation therapy and/or chemotherapy treatment
o
TNBC with skin lesions
−
Must have histologically confirmed ER, progesterone receptor, and HER2
negative breast cancer; defined as ER < 1%, progesterone receptor < 1%, and
HER2 negative according to ASCO/College of American Pathologists guidelines
by local testing according to institutional standards. Patients with weakly ER or
progesterone receptor positive disease, defined as ER and/or progesterone
receptor < 5% by IHC, are eligible, if the treating physician considers the patient
not eligible for endocrine therapy
−
Have locally advanced and locally recurrent skin or subcutaneous metastases not
suitable for definitive (or curative) surgical resection or radiotherapy
−
Received at least 1 and no more than 3 systemic chemotherapy regimens for
metastatic breast cancer and have documented disease progression on most recent
therapy
−
Willing to provide a fresh skin tumor biopsy (fixed and frozen) from a nontarget
lesion

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o
hTMB
−
Metastatic or advanced unresectable cancer with hTMB as determined using a
Clinical Laboratory Improvement Amendments validated assay (at least 16/Mb)
from a recent tumor tissue or blood sample
−
Patient has failed or refused available SOC therapy specific for their tumor type.
10.1.7. 
 
  

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10.1.8. 
Inclusion Criteria for All Patients in Parts A
 
1. Agreement to provide mandatory archival/baseline biopsy. A tumor biopsy is required at
baseline if there is no other record of histological diagnosis of tumor;
2. For patients in Part A2 or Part B2 (for Part B2, only those patients receiving 3 mg/kg of
ipilimumab), and those who agree to participate in the biomarker analysis and who have a
tumor site that is safe to biopsy, patients must have a biopsy within 90 days of study entry
and be willing to undergo at least 1 on-treatment tumor biopsy;
3. Patients with treated brain metastases are eligible if the brain metastases are stable and the
patient does not require radiation therapy or steroids. Active screening for brain metastases
(e.g., brain computed tomography [CT] or magnetic resonance imaging [MRI]) is not
required;
4. At least 18 years of age;
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
6. Anticipated life expectancy of at least 3 months;
7. Screening laboratory values must meet the following criteria:
•
White blood cells > 2000/µL or 2.0 × 109/L;
•
Neutrophils ≥ 1500/µL or 1.5 × 109/L;
•
Platelets ≥ 100 × 103/µL or 100 × 109/L;
•
Hemoglobin ≥ 9.0 g/dL (may have been transfused) or 90.0 g/L;
•
Creatinine ≤ 2 mg/dL or 176.8 µmol/L;
•
AST ≤ 2.5 × upper limit of normal (ULN); ≤ 5 × ULN for patients with liver metastasis;
< 3 × ULN for patients in Part C (vemurafenib + CX-072). No upper limit for patients
with hepatocellular carcinoma (HCC) or pancreatic cancer;
•
ALT ≤ 2.5 × ULN; ≤ 5 × ULN for patients with liver metastasis; < 3 × ULN for patients
in Part C (vemurafenib + CX-072). No ULN for patients with HCC or pancreatic cancer;
•
Total bilirubin within ULN (unless diagnosed with Gilbert’s syndrome, those patients
must have a total bilirubin < 3.0 mg/dL or 51.3 μmol/L). No upper limit for patients with
HCC; and
•
Amylase and lipase ≤ 1.5 × ULN. No upper limit for patients with pancreatic cancer;

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8. Women of childbearing potential and males must agree to use a highly effective method of
contraception (details provided in APPENDIX 5) prior to study entry, while on study drug,
and for a period of 105 days following the last treatment and for 180 days if receiving
vemurafenib;
•
Highly effective methods of contraception which result in a low failure rate
(i.e., < 1% per year) when used consistently and correctly include implants, injectables,
combined hormonal contraceptives, some intrauterine devices, sexual abstinence, or a
vasectomized partner;
o
Combined hormonal contraceptives are not a highly effective method of
contraception for patients taking vemurafenib in Part C; and
o
True abstinence, when in line with the preferred and usual lifestyle of the patient, is
considered a highly effective method only if defined as refraining from heterosexual
intercourse during the entire period of risk associated with the study treatments.
(Periodic abstinence [e.g., calendar, ovulation, symptothermal, post ovulation
methods] and withdrawal are not acceptable methods of contraception); and
9. The ability to understand and the willingness to sign a written ICF and adhere to study
schedule and prohibitions.
10.2. 
Exclusion Criteria 
Patients who fulfill any of the following criteria at screening will not be eligible for admission 
into the study. 
1. Prior therapy with a chimeric antigen receptor (CAR) T-cell containing regimen;
2. Baseline QTc is > 470 ms or taking any medication known to prolong the QT interval;
3. Prior history of myocarditis irrespective of the cause;
4. Treatment with strong cytochrome P450 (CYP) 3A4 inhibitors or inducers, as well as use
of CYP1A2 substrates with a narrow therapeutic window assigned to the vemurafenib
treatment arm. http://medicine.iupui.edu/clinpharm/ddis/main-table/;
5. History of severe allergic or anaphylactic reactions to human mAb therapy or known
hypersensitivity to any Probody therapeutic;
6. Active or history of uveal, mucosal, or ocular melanoma is excluded in Parts B2 and C;
7. History of interstitial lung disease for patients with TET;
•
Patients with TET are excluded in Parts B1 and B2;
8. Human immunodeficiency virus (HIV) or acquired immune deficiency syndrome
(AIDS)-related illness, acute or chronic hepatitis B or C; patients with HIV that have an
undetectable viral load and a CD4 cell count > 400/mL and who remain on antiretroviral
regimen will be eligible for enrollment into anal SCC cohorts in Parts D and E and hTMB
cohort in Part D;

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9. History of or current active autoimmune diseases, including but not limited to
inflammatory bowel diseases, rheumatoid arthritis, autoimmune thyroiditis, autoimmune
hepatitis, systemic sclerosis, systemic lupus erythematosus, autoimmune vasculitis,
autoimmune neuropathies, type 1 insulin dependent diabetes mellitus, or myasthenia
gravis;
10. History of syndrome or medical condition(s) that requires systemic steroids (> 10 mg daily
prednisone equivalents) or immunosuppressive medications;
11. History of allogeneic tissue/solid organ transplant, prior stem cell or bone marrow
transplant;
12. Chemotherapy, biochemotherapy, or immunotherapy or any investigational treatment
within 14 days prior to receiving any study drug; radiation therapy within 3 months prior to
receiving study medication (except for radiotherapy for the purposes of palliation confined
to a single field that is not the target lesion);
13. Patients in Part C cannot have a glomerular filtration rate < 60 mL/min/1.73 m2;
14. Major surgery (requiring general anesthesia) within 3 months or minor surgery (excluding
biopsies conducted with local/topical anesthesia) or gamma knife treatment within 14 days
(with adequate healing) of administration of any study drug;
15. Unresolved acute toxicity of the NCI CTCAE v4.03 Grade > 1 (or baseline, whichever is
greater) that may put the patient at high risk under the current treatment. Alopecia and
other nonacute toxicities are acceptable;
16. 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 and considered to have been
cured and, in the opinion of the Investigator, present a low risk for recurrence. These
exceptions include, but are not limited to, basal or squamous cell skin cancer, superficial
bladder cancer, or carcinoma in situ of the prostate, cervix or breast;
17. Received a live vaccine within 30 days prior to first dose of study drug;
18. Known pre-existing condition of age-related macular degeneration;
19. Intercurrent illness, including, but not limited to, symptomatic congestive heart failure
(i.e., New York Heart Association Class III or IV), unstable angina pectoris, clinically
significant and uncontrolled cardiac arrhythmia, nonhealing wound or ulcer, or psychiatric
illness/social situations that would limit compliance with study requirements;
20. Pleural effusion, pericardial effusion, or recurrent ascites drainage;
21. Ongoing or active infection (including fever within 48 hours of screening);
22. Participating in an ongoing clinical study involving treatment with medications, radiation,
or surgery; or
23. Women who are pregnant or breastfeeding.

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11.
INVESTIGATIONAL PRODUCT
11.1. 
Identity of Investigational Product
CX-072 is an anti–PD-L1-targeted, recombinant, protease-activatable antibody prodrug
(Probody therapeutic).
Diluent for CX-072 is a sterile solution provided specifically for use with CX-072 IP for dose 
preparation for the first 2 dose levels. 
11.2. 
Identity of Reference Therapy 
11.2.1. 
Yervoy (Ipilimumab) 
Yervoy is a human CTLA-4 blocking antibody indicated for the treatment of unresectable or 
metastatic melanoma. Yervoy is a sterile, preservative-free, clear to slightly opalescent, colorless 
to pale-yellow solution for IV infusion, which may contain a small amount of visible 
translucent-to-white, amorphous ipilimumab particulates. It is supplied in single-use vials of 
50 mg/10 mL and 200 mg/40 mL. 
11.2.2. 
Zelboraf (Vemurafenib) 
Zelboraf is a kinase inhibitor indicated for the treatment of unresectable or metastatic melanoma 
with BRAF V600E mutation as detected by an approved test. It is available as 240 mg tablets for 
oral use. Tablets are white to off-white and are supplied as 240 mg film-coated tablets with VEM 
debossed on 1 side. 
11.3. 
Packaging and Labeling of Clinical Supplies 
CX-072 is supplied as a sterile, preservative-free solution in 
 at a concentration of
 The label for CX-072 will include standard product information. It will also include
“CAUTION: New Drug – Limited by United States Law to Investigational Use.”
Diluent for CX-072 is supplied as a sterile, preservative-free solution in 
 vials. The label 
for Diluent for CX-072 will include standard product information. It will also include 
“CAUTION: New Drug – Limited by United States Law to Investigational Use.” 
Ipilimumab is supplied in single-use vials of 50 mg (5 mg/mL) and 200 mg (5 mg/mL). 
Vemurafenib is supplied as a 240 mg tablet in bottles of 120 or 112 tablets for US sites or as a 
240 mg tablet in aluminum perforated unit dose blisters in packs of 56 × 1 tablet (7 blisters of 
8 × 1 tablet per carton) for rest of the world sites. The primary packaging will remain unchanged. 
11.4. 
Storage of Clinical Supplies 

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Diluent for CX-072: Diluent vials must be stored at a temperature of 2°C to 8°C (36°F to 46°F). 
Vials should be stored in the carton. Recommended safety measures for preparation and handling 
of Diluent for CX-072 include laboratory coats and gloves. Do not freeze. 
Ipilimumab: Store under refrigeration at 2°C to 8°C (36°F to 46°F). Do not freeze. Protect vials 
from light. 
Vemurafenib: Store at room temperature 20°C to 25°C (68°F to 77°F); excursions permitted 
between 15°C and 30°C (59°F and 86°F). Store in the original container with the lid tightly 
closed. 
It is the responsibility of the Investigator to ensure that the IP and reference therapy is stored as 
specified by the Sponsor and in accordance with applicable regulatory requirements. 
11.5. 
Dosage, Study Drug Preparation, and Administration 
11.5.1. 
CX-072 
Dosage 
In the dose escalation portion of the study, CX-072 is administered by IV at a dose of 0.03, 0.1, 
0.3, 1, 3, 10, and 30 mg/kg per dose q2wk or q3wk. In Part D and the Part A, imaging substudy 
CX-072 is administered by IV at a dose of 10 mg/kg q2wk. 
Part A (monotherapy dose escalation) of the study permitted escalation up to 30 mg/kg of 
CX-072. Three patients were enrolled and dosed in the 30 mg/kg cohort and while none of the
patients had a DLT during the DLT period, 1 patient had a Grade 4 elevation of ALT and a
Grade 3 elevation of AST detected at Cycle 1 Day 42. CX-072 was discontinued, and the levels
resolved with administration of steroids. This event was assessed by the Investigator and the
Sponsor as related to CX-072. CytomX terminated further evaluation of any dosing at 30 mg/kg
of CX-072 in monotherapy and combination. Therefore, cohorts in Parts B and C that called for
combinations with CX-072 at 30 mg/kg will not be explored.
Study Drug Preparation 

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Study Drug Administration 
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. 
All infusions will be administered through a nonpyrogenic, low protein binding in-line filter 
(pore size of 0.2 µm). Following completion of the infusion, flush with an adequate amount of 
normal saline for infusion. 
Do not co-administer other drugs concurrently through the same IV line. 
CX-072 should be administered under the supervision of a physician or other study personnel
experienced in the use of IV agents.
 
 
 
  
 
 
 
 
 
Additional information on study drug preparation can be found in the Pharmacy Manual. 
11.5.1.1. 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, is discolored, or contains extraneous particulate 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. 
11.5.2. 
Yervoy (Ipilimumab) 
Ipilimumab is supplied as a sterile, preservative-free solution in 10 mL (50 mg) and 40 mL 
(200 mg) vials at a concentration of 5 mg/mL. Dosing will be based on the patient’s weight and 
dose level assignment. Ipilimumab may be diluted with 0.9% sodium chloride injection, United 
States Pharmacopeia (USP) or 5% Dextrose Injection, USP to a final concentration ranging from 
1 to 2 mg/mL. Follow the package insert for detailed information.  
 

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11.5.3. 
Zelboraf (Vemurafenib) 
Vemurafenib will be supplied in oral tablet form. Vemurafenib 960 mg will be administered in 
PO form twice daily (approximately q12h) with or without a meal.  
Patient compliance with vemurafenib dosing will be assessed throughout the study via pill counts 
and/or patient diary.  
11.6. 
Management of Infusion Reactions 
Pre-medication 
Patients will not be pre-medicated prior to the CX-072 infusion, unless the Sponsor determines 
that pre-medication is warranted.  
Patients must not receive any pre-medications prior to infusions, unless it is determined during 
the course of the study that the occurrence of infusion-related reactions (IRRs) warrants routine 
prophylactic treatment. Thereafter, patients may receive pre-medication with 650 to 1000 mg PO 
acetaminophen and/or histamine antagonists (e.g., diphenhydramine and/or ranitidine 50 mg IV 
each) at the discretion of the Investigator. Pre-medication with corticosteroids should not 
routinely be used, unless IRRs are experienced with a previous dose that required corticosteroid 
treatment, or it is later determined during the study by the Medical Monitor and Investigators that 
it would be in the best interest of patients to pre-medicate all patients with corticosteroids. 
For allergic (hypersensitivity) reactions occurring during or after study drug administration, 
follow the guidelines listed in Table 10. 
Investigators should follow their institutional guidelines for the treatment of anaphylaxis. 

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Table 10: 
Management of Allergic Reactions 
Grade of Allergic Reaction 
Treatment 
Grade 1: Transient flushing or rash, drug fever 
< 38°C (< 100.4°F). 
Remain at bedside and monitor patient until recovery from 
symptoms.  
Grade 2: Intervention or infusion interruption 
indicated; responds promptly to symptomatic 
treatment (e.g., antihistamines, NSAIDS, narcotics); 
prophylactic medications indicated for ≤ 24 hours. 
Stop the CX-072 infusion, begin an IV infusion of normal saline 
and treat the patient with diphenhydramine 50 mg IV (or 
equivalent) and/or paracetamol 325-1000 mg PO; remain at 
bedside and monitor patient 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 patient closely. If 
symptoms recur, then the infusion should be discontinued and 
no further CX-072 will be administered at that visit. Administer 
diphenhydramine 50 mg IV and remain at bedside and monitor 
the patient until resolution of symptoms. 
Pre-medication will be instituted in patients who experience an 
allergic reaction to IP. 
Grade 3: Prolonged (e.g., > 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 (e.g., renal 
impairment, pulmonary infiltrates). 
Immediately discontinue infusion of CX-072. Begin an IV 
infusion of normal saline, and treat the patient as follows:  
• Recommend bronchodilators, epinephrine 0.2 to 1 mg of a
1:1,000 solution for subcutaneous administration or 0.1 to
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.
Patient should be monitored until the Investigator is
comfortable that the symptoms will not recur.
• CX-072 will be permanently discontinued for prolonged
Grade 3 allergic reaction, 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.
Grade 4: Life-threatening consequences; urgent 
intervention indicated. 
Follow treatment for Grade 3 allergic reaction and monitor 
patient until recovery from symptoms. CX-072 will be 
permanently discontinued. 
AE = adverse event; IP = investigational product; IV = intravenous; NSAID = nonsteroidal anti-inflammatory drug; 
PO = oral. 
During an infusion reaction, vital signs will be obtained every 2 to 5 minutes until stable. In the 
case of late-occurring hypersensitivity symptoms (e.g., appearance of a localized or generalized 
pruritus within 1 week after treatment), symptomatic treatment may be given (e.g., oral 
antihistamine or corticosteroids). 

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12.
DOSE MODIFICATIONS OR MISSED DOSES
There must be a minimum of 14 days between study drug infusions. In exceptional 
circumstances, an infusion may be delayed for up to 7 days. Infusions that cannot be 
administered in that time frame will be considered a missed dose and the patient should come in 
for their next, regularly scheduled visit, relative to Day 1. A patient will be considered to have 
discontinued study drug if he/she misses 4 consecutive doses.1  
12.1. 
Data Safety Monitoring Board 
The Data Safety Monitoring Board (DSMB) will monitor the safety of the study for  
Parts A
. The DSMB will consist of individuals in relevant fields of expertise. It will convene 
on a regular basis (at least 2 times per year) and will review all safety and efficacy information to 
determine whether the study should continue unchanged or whether protocol modifications are 
required to ensure patient safety. Details on the DSMB are provided in APPENDIX 3 and in a 
separate DSMB charter. The DSMB will make recommendations to the Sponsor, who will make 
ultimate decisions regarding study alteration or discontinuation. 
12.1.1. 
Dose Modifications for CX-072 Adverse Events 
The following guidance is for dose modification of CX-072 and also addresses conditions 
outside of their respective labels in which ipilimumab or vemurafenib dosing would be reduced 
or discontinued. 
Dose reduction of CX-072 is not permitted. Delays or permanent discontinuation of CX-072 may 
be required as dictated in Table 11. 
1 For patients who are responding to treatment, the Medical Monitor should be notified to discuss the treatment 
delay and whether study drug may be re-started. 

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Table 11: 
Dose Modifications for CX-072 
Adverse Event 
Withhold CX-072 
Permanently Discontinue 
CX-072
Pneumonitis 
Grade 2 
Grade 3 or 4 
Colitis 
Grade 2 or 3 
Grade 4 
AST or ALT 
> 3 and up to 5 × ULN
> 5 × ULN
Total bilirubin 
> 1.5 and up to 3 × ULN
> 3 × ULN
Creatinine 
> 1.5 and up to 6 × ULN or
greater than 1.5 × baseline
> 6 × ULN
Hypophysitis 
Symptomatic 
-- 
Myocarditis 
Any 
-- 
Ocular inflammatory toxicity 
Grade 2 
Grade 3 or 4 
Hyperthyroidism 
Grade 3 
-- 
Any other severe or Grade 3 
treatment-related adverse 
reaction 
Withhold1 
Any severe or Grade 3 
treatment-related AE that recurs; 
Grade 4 
Life-threatening or Grade 4 
adverse reaction 
-- 
Permanently discontinue 
Grade 3 or 4 immune-related 
adverse reaction 
Grade 3 
Withhold and contact Sponsor’s 
Medical Monitor to discuss 
treatment, which may include 
administration of systemic 
steroids 
Grade 4 
Permanently discontinue and 
contact Sponsor’s Medical 
Monitor to discuss treatment, 
which may include 
administration of systemic 
steroids 
1Excluding amylase or lipase elevations. 
This table is general guidance. If a laboratory value is elevated at baseline, the Medical Monitor should be contacted for 
dosing adjustments. 
AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; ULN = upper limit of normal. 
Resume CX-072 in patients whose adverse reactions recover to Grade 0 to 1 within 2 weeks or at 
the discretion of the Investigator.  
In the event of a major surgery (biopsy excluded) the patient should be discontinued from the 
study. 
CX-072 should be permanently discontinued for any of the following:
•
Inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per
day within 12 weeks of initiation, or
•
Persistent Grade 2 or 3 treatment-related adverse reactions that do not recover to Grade 1
or resolve within 12 weeks after the last dose of CX-072.

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Additional guidelines for the management of AEs follow: 
Immune-mediated pneumonitis 
Monitor patients for signs and symptoms of pneumonitis. For ≥ Grade 2 pneumonitis, 
recommend treatment with corticosteroids at a dose of 1 to 2 mg/kg/day prednisone equivalents, 
followed by a corticosteroid taper. Withhold CX-072 for Grade 2 immune-mediated pneumonitis 
and permanently discontinue treatment for Grade 3 or 4 or recurrent pneumonitis upon restarting 
CX-072.
Immune-mediated colitis
For severe (Grade 3) or life-threatening (Grade 4) colitis, administer corticosteroids at a dose of 
1.5 to 2 mg/kg/day prednisone equivalents followed by corticosteroid taper. For moderate 
(Grade 2) colitis of > 5 days in duration, administer corticosteroids at 0.5 to 1 mg/kg/day 
prednisone equivalents followed by corticosteroid taper. For Grade 2 colitis that worsens or does 
not improve after initiation of corticosteroids, increase dose of corticosteroids to 1 to 
2 mg/kg/day prednisone equivalents. Withhold CX-072 for Grade 2 or 3 immune-mediated 
colitis and permanently discontinue treatment for Grade 4 or recurrent colitis upon restarting 
CX-072.
Immune-mediated hepatitis
Monitor patients for abnormal liver tests prior to and periodically during treatment. Administer 
corticosteroids 1 to 2 mg/kg/day prednisone equivalents for Grade 2 or greater transaminase 
elevations, with or without concomitant elevation in total bilirubin. Withhold CX-072 for 
Grade 2 and permanently discontinue for Grade 3 or Grade 4 immune-mediated hepatitis. 
Immune-mediated hypothyroidism and hyperthyroidism 
Monitor thyroid function prior to and periodically (every 3 months and as clinically indicated) 
during treatment. Administer hormone replacement therapy for hypothyroidism. Initiate medical 
management for control of hyperthyroidism. There are no recommended dose adjustments of 
CX-072 for hypothyroidism or hyperthyroidism.
Myocarditis
Monitor patients for myocarditis prior to and periodically during treatment. In case of newly 
occurring signs of arrhythmia, discontinue CX-072 and ipilimumab until myocarditis and/or 
acute heart failure is ruled out. 
Other immune-mediated adverse reactions 
For any suspected immune-mediated adverse reactions, exclude other causes. Based on the 
severity of the adverse reaction, withhold CX-072, administer high-dose corticosteroids, and if 
appropriate, initiate hormone-replacement therapy. Upon improvements to Grade 1 or less, 
initiate corticosteroid taper and continue 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 CX-072–related AEs 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 factor-α inhibitors may be administered at the discretion of the Investigator. 

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12.1.2. 
Special Instructions Regarding Dose Modification of Ipilimumab or 
Vemurafenib 
For dose modification of ipilimumab and vemurafenib, the Investigator is directed to the 
respective package inserts.  
•
Ipilimumab: Yervoy US Package Insert, 2015; and
•
Vemurafenib: Zelboraf US Package Insert, 2016.
See Section 12.1.1 for dose modification of CX-072 and conditions outside of their respective 
labels in which ipilimumab or vemurafenib dosing would be reduced or discontinued. 
If CX-072 is discontinued, ipilimumab or vemurafenib, as applicable, will also be discontinued. 
Delays in CX-072 treatment will also result in a delay of ipilimumab or vemurafenib, until a 
maximum of 4 doses of ipilimumab have been administered. 
CX-072 treatment may continue in the event of a noninflammatory event that, in the judgment of
the Investigator, is due to vemurafenib. However, in the event that the event does not improve
after vemurafenib dosing adjustments, CX-072 will be adjusted as per the protocol.
Additional modifications of ipilimumab and vemurafenib may be performed at the discretion of 
the Investigator after discussion with the Medical Monitor. 

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13.
PRIOR AND 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 
electronic case report form (eCRF).  
1. Patients enrolled to the CX-072/vemurafenib arm of the study should avoid concomitant
administration of vemurafenib with strong CYP3A4 inhibitors or inducers, as well as
concomitant use with CYP1A2 substrates with a narrow therapeutic window. Patients
taking concomitant moderate CYP inhibitors or inducers during the study should be
monitored for possible complications (P450 Drug Interaction Table 2015);
2. Inhaled or intranasal corticosteroids (with minimal systemic absorption) may be continued
if the patient is on a stable dose. Nonabsorbed intra-articular steroid injections will be
permitted. Systemic corticosteroids required for the control of infusion reactions or irAEs
must be tapered and be at nonimmunosuppressive doses (≤ 10 mg/day of prednisone or
equivalent) for at least 2 weeks before the next study drug administration (if authorized by
the study physician). The use of steroids as prophylactic treatment for patients with contrast
allergies to diagnostic imaging contrast dyes will be permitted;
3. The use of herbal remedies (herbal preparation in the Chinese traditional medicine), other
marketed anti-cancer chemo/immunotherapy/hormonal drugs, or investigational drugs is
not permitted;
4. New chemotherapy, hormonal (exception allowed for prostate cancer patients receiving
androgen deprivation therapy or pre-menopausal women receiving gonadotropin-releasing
hormone [GnRH] agonists), radiation or immunotherapy is not permitted during the
screening or treatment periods;
5. Palliative/therapeutic therapies (e.g., focal radiotherapy for pain, thoracentesis or
paracentesis for comfort) are permitted after consultation with the Medical Monitor;
6. The use of live vaccines while on study drug is prohibited. 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 on the patient’s records and in the
eCRF; and
7. Co-administration of bisphosphonates and denosumab is permitted for patients being
administered bisphosphonates and denosumab prior to the study. These drugs should be
continued at the same dose during the study.
All concomitant medications taken by the patient while in the study should be recorded in the 
eCRF. Once a patient enters the follow-up period, only new therapies for the treatment of their 
cancer should be recorded in the eCRF. 

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14.
PHAMACOKINETIC, IMMUNOGENICITY, AND
EXPLORATORY BIOMARKER ASSESSMENTS
14.1. 
Pharmacokinetic Assessments 
Concentration versus time data will be tabulated and plotted for the individual and mean serum 
total and intact CX-072 moieties. PK parameters including AUC, Cmax, time to reach Cmax, Cmin, 
clearance, and volume of distribution at steady state will be calculated for total and intact 
CX-072 moieties as appropriate and as data allow. Additional parameters such as t1/2 and
accumulation may be calculated, and dose proportionality will be assessed. Estimates for these
parameters will be tabulated and summarized (e.g., mean, standard deviation, and coefficient of
variation).
Vemurafenib Cmax and Cmin and ipilimumab Cmax and Cmin will be summarized using descriptive 
statistics.  
14.1.1. 
Pharmacokinetics Collection 
Samples should be drawn from a site other than the infusion site (i.e., contralateral arm) on days 
of infusion. Times noted are post end of infusion (EOI). The full schedule of PK blood sampling 
can be found in Table 17.  
The date and time of each dose administered and the times at which PK samples are collected 
should be recorded in the eCRF. 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 EOI. 
14.2. 
Immunogenicity Assessments 
Serum samples will be collected from study participants, as described in Table 12, Table 13, 
Table 14, and Table 15 to assess the immunogenicity of CX-072 and ipilimumab (when 
ipilimumab is administered). Samples will be initially screened for ADA to CX-072 and 
ipilimumab (when ipilimumab is administered). 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 
ADAs. Incidence of ADA response and the potential correlation with PK, PD, and safety 
parameters may be assessed. 
14.2.1. 
Immunogenicity Collection 
The full schedule of ADA blood sampling can be found in Table 12, Table 13, Table 14, and 
Table 15. 
 
 
 
 
 

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15.
STUDY PROCEDURES AND SCHEDULE OF EVENTS
The study procedures to be followed are outlined in the Schedules of Events. Refer to the 
Common Core Document for a description of each procedure.

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Table 12: 
Schedule of Events: Parts A and D: CX-072 Monotherapy and Part C: CX-072 Plus Vemurafenib 
Period/Procedure 
Screening 
Period 
Treatment Period 
Cycle 1 
± 2 days of scheduled visit 
Cycles 2 – n 
± 2 days of scheduled visit 
EOT 
Study/Visit Day1
-30 to 0
Day 
1 
Day 
2 
Day 
8 
Day 
15 
Day 
29 
Day 
43 
Day 
562 
Day 
1 
Day 
15 
Day 
29 
Day 
43 
Day 
562 
Informed Consent 
X 
Medical History3 
X 
Prior Treatment/Therapies for Cancer 
X 
Demographics 
X 
AE Assessment4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Limited Resource Utilization 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study Drug Administration 
CX-072 Infusion5
X 
X 
X 
X 
X 
X 
X 
X 
Vemurafenib Oral Tablets6 
960 mg twice daily approximately 12 hours apart 
Imaging 
CT/MRI (chest, abdomen, pelvis)7 
X 
Every 8 weeks for 12 months then every 12 weeks 
X 
PET/CT or PET with Diagnostic CT8 
X 
Every 8 weeks for 12 months then every 12 weeks 
X 
Bone Scan9 
X 
Every 8 weeks for 12 months then every 12 weeks 
X 
ECG10 
X 
X 
X11 
X11 
X11 
X11 
X11 
Clinical Procedures 
Physical Examination12 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs13 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECOG Performance Status14 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height13 
X 
Weight13 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Table 12: 
Schedule of Events: Parts A and D: CX-072 Monotherapy and Part C: CX-072 Plus Vemurafenib (Continued) 
Period/Procedure 
Screening 
Period 
Treatment Period 
Cycle 1 
± 2 days of scheduled visit 
Cycles 2 – n 
± 2 days of scheduled visit 
EOT 
Study/Visit Day1 
-30 to 0
Day 
1 
Day 
2 
Day 
8 
Day 
15 
Day 
29 
Day 
43 
Day 
562 
Day 
1 
Day 
15 
Day 
29 
Day 
43 
Day 
562 
B Symptoms15 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Diagnosis Confirmation, Stage and Baseline 
Disease Assessment and Documentation16 
X 
Tumor Response Assessment16 
X 
Every 8 weeks for 12 months then every 12 weeks 
X 
Laboratory Assessments 
ACTH 
X 
Hematology17 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum Chemistry18 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Thyroid Function19 
X 
Every 3 months 
X 
HIV, Hepatitis B and C20 
X 
Coagulation21 
X 
X 
X 
Urinalysis22 
X 
X 
X 
X 
Pregnancy Test23 
X 
X 
X 
X 
X 
X 
Archival/Baseline Biopsy24 
X 
Sample for PK 
PK samples for CX-072 will be collected for Parts A, C, and D according to Table 17. 
PK will be collected for vemurafenib according to Table 17. 
Serum sample for ADA27 
X 
X 
X 
X 
X 
Blood sample for tumor mutation burden28 
X 
Blood sample for TET safety monitoring29 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood sample for CEA and CA 19-130 
X 
Every 8 weeks for 12 months then every 12 weeks 
X 

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ACTH = adrenocorticotropic hormone; ADA = anti-drug antibody; AE = adverse event; ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; 
AST = aspartate aminotransferase; BUN = blood urea nitrogen; CA 19-9 = cancer antigen 19-9; CBC = complete blood count; CEA = carcinoembryonic antigen; CRC = colorectal cancer; 
CT = computed tomography; CV = cardiovascular; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EOI = end of infusion; EOS = end of study; EOT = end of treatment; 
GI = gastrointestinal; HCG = human chorionic gonadotropin; HIV = Human Immunodeficiency Virus; hTMB = high tumor mutational burden; INR = international normalized ratio; 
IP = investigational product; IV = intravenous; LDH = lactate dehydrogenase; mCRPC = metastatic castration-resistant prostate cancer; MEL = melanoma; MRI = magnetic resonance imaging; 
NSCLC = non-small cell lung cancer; PD = pharmacodynamics; PET = positron emission tomography; PK = pharmacokinetics; PT = prothrombin time; qXwk = every X weeks; RCC = renal cell 
carcinoma; SCC = squamous cell carcinoma; SGOT = serum glutamic-oxaloacetic transaminase; SGPT = serum glutamic-pyruvic transaminase; T3 = triiodothyronine; T4 = thyroxine; 
TET = thymic epithelial tumor; TNBC = triple negative breast cancer; TSH = thyroid-stimulating hormone. 
1.
Study visits that cannot occur on the scheduled day due to unforeseen circumstances other than toxicity (e.g., 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. Visits conducted outside the windows are to be discussed with the Medical Monitor in advance.
2.
This is not a clinic visit; this is for radiologic assessment and response assessment by the Investigator prior to beginning the next cycle of treatment. These assessments should occur between
-3 days and the indicated day, and before administering the first dose of the next cycle of treatment.
3.
To include confirmation of previous cancer diagnosis and recording cancer treatment history, current symptoms at baseline (defined as value at screening), and medications currently being
taken.
4.
Adverse events and concomitant medications will be assessed and reviewed prior to infusion and at any other visit that includes a physical examination. Once study drug is discontinued,
only new medications for the treatment of the patient’s cancer need to be recorded, as applicable during follow-up.
5.
If a ≥ Grade 2 infusion-related reaction is observed during or after an infusion, a local blood draw is required to measure tryptase, total immunoglobulin E, and complement C3a and C5
preferably within 2 hours and no more than 6 hours after the first signs/symptoms of the reaction.
6.
Only administered in Part C CX-072 + vemurafenib.
7.
CT and/or MRI to be performed within 30 days prior to the first dose of CX-072 and repeated q8wk (Day 0 to 12 months) and then q12wk (Month 13 to 24). Scans will also be repeated at
the EOT visit and, if applicable, at the EOS visit (i.e., if the patient has not experienced progression). Methodology used should remain consistent for the duration of patient participation in
the study.
8.
Lymphoma patients only. Methodology used to evaluate lesions should remain consistent for the duration of patient participation in the study.
9.
Bone scans must be done at all visits indicated for patients with mCRPC. For patients with MEL, RCC, CRC, and NSCLC, perform bone scan at baseline (defined as value at screening) or
at response assessment visits as clinically indicated. Collect and hold scans for review by an independent committee.
10.
12-lead ECGs should be obtained in triplicate (approximately 2 to 5 minutes apart), in digital format (when possible) and archived, while supine at screening, at defined time points, at the
EOT visit, and as clinically indicated.
11.
For patients in Part A: perform ECG at screening, 30 (± 15) minutes before and after CX-072 infusions on Cycle 1 Day 1, Cycle 2 Day 1, Cycle 2 Day 29, and at the EOT visit. For patients
in Part C: perform ECG at screening, 30 (± 15) minutes before and after CX-072 infusions on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 29, Cycle 2 Day 1, Cycle 2 Day 29, and again
every 2 cycles thereafter, or more often as clinically indicated, and at the EOT visit. For patients in Part D: perform ECG at screening, 30 (± 15) minutes before and after CX-072 infusions
on Cycle 1 Day 1, Cycle 2 Day 29, and at the EOT visit.
12.
Physical examinations should be performed at screening and on Day 1, on each day of Probody therapeutic dosing, and at the EOT visit. At all other visits, targeted physical examinations
should be performed as needed by patient symptoms or clinical observations, focused on key organ systems of interest (e.g., CV, pulmonary, GI, skin, ophthalmic, endocrine, or any systems
with previously noted abnormal findings). Dermatologic evaluations should be performed prior to initiation of therapy and every 2 months while on therapy. Dermatologic monitoring for
6 months following discontinuation of vemurafenib is recommended.
13.
Vital signs include heart rate and blood pressure (supine), temperature, respiratory rate, and pulse oximetry. During the first 4 doses of IP, vital signs should be measured within
60 (± 5) minutes prior to infusion, every 15 (± 5) minutes during infusion, at the EOI (± 5 minutes), and approximately hourly for 4 hours (± 5 minutes) after the completion of infusion. On
all other infusion days, vital signs should be measured within 60 (± 5) minutes prior to infusion, at the EOI (± 5 minutes), and 60 (± 5) minutes after completion of infusion (unless clinical
signs require more frequent monitoring). For CX-072 doses administered via IV push, vital signs will be measured pre-dose (± 5 minutes), at the end of the injection (± 5 minutes), and then
as per the schedule above. Weight should be measured at screening and before each dose. Height should be measured at screening only. During an infusion reaction, vital signs should be
recorded every 2 to 5 minutes until stable.
14.
Performance status should be assessed at screening, Day 1 and prior to each subsequent infusion, and at EOT visit.
15.
Lymphoma patients only, B symptoms: fever, chills, fatigue, night sweats, weight loss, and pruritus.
16.
Tumor measurements will be recorded at baseline (defined as value at screening) and repeated q8wk (from Dose 1 for 12 months), then q12wk until EOT and at the EOT visit; refer to
tumor-specific response criteria guidelines in the Common Core Document. The patient will be re-baselined at the initial/unconfirmed progression. For TNBC patients with skin lesions, skin
lesions must be photographed along with a ruler at all time points for tumor assessments. Methodology used for tumor assessments should remain consistent for the duration of patient
participation in the study.

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17.
Including CBC with differential, including blast count, platelet count pre-dose.
18.
Including alkaline phosphatase, AST/SGOT and ALT/SGPT, amylase, lipase, total bilirubin, calcium, phosphorus, BUN, creatinine, total protein, albumin, glucose, potassium, sodium,
chloride, bicarbonate, uric acid, magnesium, and LDH. Blood glucose should be fasting to evaluate possible hyperglycemia. Calculated creatinine clearance is required at screening.
Laboratory assessments drawn on the day of infusion should be drawn pre-dose.
19.
Including TSH, free T4 and T3. Thyroid function will be assessed at baseline (defined as value at Cycle 1 Day 1), every 3 months during treatment, at the discretion of the Investigator, and
at the EOT visit.
20.
HIV positive patients in Part D anal SCC and hTMB cohorts need to have their CD4 count and viral load captured at screening to ensure eligibility criteria have been met.
21.
Including PT/aPTT/INR at screening, and pre-dose Day 1, at EOT visit, and as clinically indicated.
22.
Urinalysis (including assessment of protein, blood, leukocytes, glucose, ketones, bilirubin, urobilinogen, pH, and specific gravity) with microscopic examination at screening, Day 1 of each
cycle, and the EOT visit.
23.
Serum pregnancy test (HCG) should be evaluated in all women of childbearing potential at screening (if 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 monthly (i.e., q4wk) while on treatment, and at the EOT visit.
24.
Central pathology review is required for patients with TNBC with skin lesions, TET, and UPS (prior to enrollment for UPS).
27.
ADA samples will be on Cycle 1 Day 1, Cycle 1 Day 29, Cycle 2 Day 1, Cycle 2 Day 29, Cycle 4 Day 29, and on Day 29 of every 4 cycles thereafter (e.g., Cycle 8 Day 29, Cycle 12
Day 29, etc.) prior to each CX-072 dose, at EOT, and > 90 days following EOT.
28.
For patients in Part D, a 16 mL blood sample will be drawn to test for tumor mutation burden at screening.
29.
For patients in Part A and Part D, all patients with TET will be screened for acetylcholine receptor autoantibodies, muscle-specific tyrosine kinase autoantibodies, and anti-skeletal muscle
antibodies at screening, Cycle 1 Day 1, Cycle 1 Day 15, Cycle 1 Day 29, Cycle 1 Day 43, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 2 Day 29, Cycle 2 Day 43, Cycle 3 Day 1, Cycle 3 Day 15,
Cycle 3 Day 29, Cycle 3 Day 43, and EOT.
30.
For patients in Part D with small bowel adenocarcinoma, a blood sample will be drawn at baseline and repeated q8wk (from Dose 1 for 12 months), then q12wk until EOT and at the EOT
visit for measurement of CEA and CA 19-9.
Patients will be followed approximately every 3 months for progression and overall survival (± 14 days) after the last dose of IP, or until withdrawal from study participation or death, whichever 
occurs first. An EOT visit will be conducted at the conclusion of treatment. The initial follow-up visit should be scheduled approximately 28 days after the patient’s last study drug administration. 
Refer to Table 16. Toxicity management may require additional visits at the discretion of the Investigator. 

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Table 13: 
Schedule of Events: Part A2: CX-072 Monotherapy 
Period/Procedure 
Screening 
Period 
Treatment Period 
Cycle 1 
± 2 days of scheduled visit 
Cycles 2 – n 
± 2 days of scheduled visit 
EOT 
Study/Visit Day1
-30 to 0
Day 
1 
Day 
2 
Day 
8 
Day 
15 
Day 
29 
Day 
43 
Day 
562 
Day 
1 
Day 
15 
Day 
29 
Day 
43 
Day 
562 
Informed Consent 
X 
Medical History3 
X 
Prior Treatment/Therapies for Cancer 
X 
Demographics 
X 
AE Assessment4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Limited Resource Utilization 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study Drug Administration 
CX-072 Infusion5
X 
X 
X 
X 
X 
X 
X 
X 
Imaging 
CT/MRI (chest, abdomen, pelvis)6 
X 
Every 8 weeks for 12 months then every 12 weeks 
X 
PET/CT or PET with Diagnostic CT7 
X 
Every 8 weeks for 12 months then every 12 weeks 
X 
Bone Scan8 
X 
Every 8 weeks for 12 months then every 12 weeks 
X 
ECG9 
X 
X 
X 
X 
X 
Clinical Procedures 
Physical Examination10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs11 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECOG Performance Status12 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height11 
X 
Weight11 
X 
X 
X 
X 
X 
X 
X 
X 
X 
B Symptoms13 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Table 13: 
Schedule of Events: Part A2: CX-072 Monotherapy (Continued) 
Period/Procedure 
Screening 
Period 
Treatment Period 
Cycle 1 
± 2 days of scheduled visit 
Cycles 2 – n 
± 2 days of scheduled visit 
EOT 
Study/Visit Day1 
-30 to 0
Day 
1 
Day 
2 
Day 
8 
Day 
15 
Day 
29 
Day 
43 
Day 
562 
Day 
1 
Day 
15 
Day 
29 
Day 
43 
Day 
562 
Diagnosis Confirmation, Stage and Baseline 
Disease Assessment and Documentation14 
X 
Tumor Response Assessment14 
X 
Every 8 weeks for 12 months then every 12 weeks 
X 
Laboratory Assessments 
ACTH 
X 
Hematology15 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum Chemistry16 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Thyroid Function17 
X 
Every 3 months 
X 
HIV, Hepatitis B and C 
X 
Coagulation18 
X 
X 
X 
Urinalysis19 
X 
X 
X 
X 
Pregnancy Test20 
X 
X 
X 
X 
X 
X 
Archival/Baseline Biopsy 
X 
Sample for PK 
PK samples for CX-072 will be collected for Part A2 according to Table 17. 
Serum sample for ADA23 
X 
X 
X 
X 
X 
Blood sample for TET safety monitoring24 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ACTH = adrenocorticotropic hormone; ADA = anti-drug antibody; AE = adverse event; ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; 
AST = aspartate aminotransferase; BUN = blood urea nitrogen; CBC = complete blood count; CRC = colorectal cancer; CT = computed tomography; CV = cardiovascular; 
ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EOI = end of infusion; EOS = end of study; EOT = end of treatment; GI = gastrointestinal; HCG = human chorionic 
gonadotropin; HIV = Human Immunodeficiency Virus; INR = international normalized ratio; IP = investigational product; LDH = lactate dehydrogenase; 
mCRPC = metastatic castration-resistant prostate cancer; MEL = melanoma; MRI = magnetic resonance imaging; NSCLC = non-small cell lung cancer; PD = pharmacodynamics; 
PET = positron emission tomography; PK = pharmacokinetics; PT = prothrombin time; qXwk = every X weeks; RCC = renal cell carcinoma; SGOT = serum glutamic-oxaloacetic transaminase; 
SGPT = serum glutamic-pyruvic transaminase; T3 = triiodothyronine; T4 = thyroxine; TET = thymic epithelial tumor; TSH = thyroid-stimulating hormone. 

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1.
Study visits that cannot occur on the scheduled day due to unforeseen circumstances other than toxicity (e.g., 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. Visits conducted outside the windows are to be discussed with the Medical Monitor in advance.
2.
This is not a clinic visit; this is for radiologic assessment and response assessment by the Investigator prior to beginning the next cycle of treatment. These assessments should occur between
-3 days and the indicated day, and before administering the first dose of the next cycle of treatment.
3.
To include confirmation of previous cancer diagnosis and recording cancer treatment history, current symptoms at baseline (defined as value at screening), and medications currently being
taken.
4.
Adverse events and concomitant medications will be assessed and reviewed prior to infusion and at any other visit that includes a physical examination. Once study drug is discontinued,
only new medications for the treatment of the patient’s cancer need to be recorded, as applicable during follow-up.
5.
If a ≥ Grade 2 infusion-related reaction is observed during or after an infusion, a local blood draw is required to measure tryptase, total immunoglobulin E, and complement C3a and C5
preferably within 2 hours and no more than 6 hours after the first signs/symptoms of the reaction.
6.
CT and/or MRI to be performed within 30 days prior to the first dose of CX-072 and repeated q8wk (Day 0 to 12 months) and then q12wk (Month 13 to 24). Scans will also be repeated at
the EOT visit and, if applicable, at the EOS visit (i.e., if the patient has not experienced progression). Methodology used should remain consistent for the duration of patient participation in
the study.
7.
Lymphoma patients only. Methodology used to evaluate lesions should remain consistent for the duration of patient participation in the study.
8.
Bone scans must be done at all visits indicated for patients with mCRPC. For patients with MEL, RCC, CRC, and NSCLC, perform bone scan at baseline (defined as value at screening) or
at response assessment visits as clinically indicated. Collect and hold scans for review by an independent committee.
9.
12-lead ECGs should be obtained in triplicate (approximately 2 to 5 minutes apart), in digital format (when possible) and archived, while supine at screening, 30 (± 15) minutes before and
after CX-072 infusions on Cycle 1 Day 1, Cycle 2 Day 1, Cycle 2 Day 29, and at the EOT visit.
10.
Physical examinations should be performed at screening and on Day 1, on each day of Probody therapeutic dosing, and at the EOT visit. At all other visits, targeted physical examinations
should be performed as needed by patient symptoms or clinical observations, focused on key organ systems of interest (e.g., CV, pulmonary, GI, skin, ophthalmic, endocrine, or any systems
with previously noted abnormal findings). Dermatologic evaluations should be performed prior to initiation of therapy and every 2 months while on therapy.
11.
Vital signs include heart rate and blood pressure (supine), temperature, respiratory rate, and pulse oximetry. During the first 4 doses of IP, vital signs should be measured within
60 (± 5) minutes prior to infusion, every 15 (± 5) minutes during infusion, at the EOI (± 5 minutes), and approximately hourly for 4 hours (± 5 minutes) after the completion of infusion. On
all other infusion days, vital signs should be measured within 60 (± 5) minutes prior to infusion, at the EOI (± 5 minutes), and 60 (± 5) minutes after completion of infusion (unless clinical
signs require more frequent monitoring). Weight should be measured at screening and before each dose. Height should be measured at screening only. During an infusion reaction, vital
signs should be recorded every 2 to 5 minutes until stable.
12.
Performance status should be assessed at screening, Day 1 and prior to each subsequent infusion, and at EOT visit.
13.
Lymphoma patients only, B symptoms: fever, chills, fatigue, night sweats, weight loss, and pruritus.
14.
Tumor measurements will be recorded at baseline (defined as value at screening) and repeated q8wk (from Dose 1 for 12 months), then q12wk until EOT and at the EOT visit; refer to
tumor-specific response criteria guidelines in the Common Core Document. The patient will be re-baselined at the initial/unconfirmed progression. Methodology used for tumor assessments
should remain consistent for the duration of patient participation in the study.
15.
Including CBC with differential, including blast count, platelet count pre-dose.
16.
Including alkaline phosphatase, AST/SGOT and ALT/SGPT, amylase, lipase, total bilirubin, calcium, phosphorus, BUN, creatinine, total protein, albumin, glucose, potassium, sodium,
chloride, bicarbonate, uric acid, magnesium, and LDH. Blood glucose should be fasting to evaluate possible hyperglycemia. Calculated creatinine clearance is required at screening.
Laboratory assessments drawn on the day of infusion should be drawn pre-dose.
17.
Including TSH, free T4 and T3. Thyroid function will be assessed at baseline (defined as value at Cycle 1 Day 1), every 3 months during treatment, at the discretion of the Investigator, and
at the EOT visit.
18.
Including PT/aPTT/INR at screening, and pre-dose Day 1, at EOT visit, and as clinically indicated.
19.
Urinalysis (including assessment of protein, blood, leukocytes, glucose, ketones, bilirubin, urobilinogen, pH, and specific gravity) with microscopic examination at screening, Day 1 of each
cycle, and the EOT visit.
20.
Serum pregnancy test (HCG) should be evaluated in all women of childbearing potential at screening (if 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 monthly (i.e., q4wk) while on treatment, and at the EOT visit.
23.
ADA samples will be on Cycle 1 Day 1, Cycle 1 Day 29, Cycle 2 Day 1, Cycle 2 Day 29, Cycle 4 Day 29, and on Day 29 of every 4 cycles thereafter (e.g., Cycle 8 Day 29, Cycle 12
Day 29, etc.) prior to each CX-072 dose, at EOT, and > 90 days following EOT.

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24.
All patients with TET will be screened for acetylcholine receptor autoantibodies, muscle-specific tyrosine kinase autoantibodies, and anti-skeletal muscle antibodies at screening, Cycle 1
Day 1, Cycle 1 Day 15, Cycle 1 Day 29, Cycle 1 Day 43, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 2 Day 29, Cycle 2 Day 43, Cycle 3 Day 1, Cycle 3 Day 15, Cycle 3 Day 29, Cycle 3 Day 43,
and EOT.
Patients will be followed approximately every 3 months for progression and overall survival (± 14 days) after the last dose of IP, or until withdrawal from study participation or death, whichever 
occurs first. An EOT visit will be conducted at the conclusion of treatment. The initial follow-up visit should be scheduled approximately 28 days after the patient’s last study drug administration. 
Refer to Table 16. Toxicity management may require additional visits at the discretion of the Investigator. 

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Table 14: 
Schedule of Events: Parts B1 and B2: CX-072 Plus Ipilimumab Combination 
Period/Procedure 
Screening 
Period 
Treatment Period 
Cycle 11 
± 2 days of scheduled visit 
Cycle 21 
± 2 days of scheduled visit 
Cycles 3 – n 
± 2 days of scheduled visit 
EOT 
Study/Visit Day2
-30 to 0
Day 
1 
Day 
2 
Day 
8 
Day 
15 
Day 
22 
Day 
29 
Day 
36 
Day 
43 
Day 
50 
Day 
573 
Day 
64 
Day 
71 
Day 
774 
Day 
1 
Day 
15 
Day 
29 
Day 
43 
Day 
563 
Informed Consent 
X 
Medical History5 
X 
Prior Treatment/Therapies for 
Cancer 
X 
Demographics 
X 
AE Assessment6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant Medications6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Limited Resource Utilization 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study Drug Administration 
CX-072 Infusion7
X 
X 
X 
X 
X 
X 
X 
X 
Ipilimumab Infusion 
X 
X 
X 
X 
D/C 
Imaging 
CT/MRI (chest, abdomen, 
pelvis)8 
X 
Scan every 8 weeks for 12 months and then every 12 weeks 
X 
PET/CT or PET with 
Diagnostic CT9 
X 
Scan every 8 weeks for 12 months and then every 12 weeks 
X 
Bone Scan10 
X 
Scan every 8 weeks for 12 months and then every 12 weeks 
X 
ECG11 
X 
X 
X 
X 
Clinical Procedures 
Physical Examination12 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital Signs13 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECOG Performance Status14 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height13 
X 
Weight13 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Table 14: 
Schedule of Events: Parts B1 and B2: CX-072 Plus Ipilimumab Combination (Continued) 
Period/Procedure 
Screening 
Period 
Treatment Period 
Cycle 11 
± 2 days of scheduled visit 
Cycle 21 
± 2 days of scheduled visit 
Cycles 3 – n1 
± 2 days of scheduled visit 
EOT 
Study/Visit Day2 
-30 to 0
Day 
1 
Day 
2 
Day 
8 
Day 
15 
Day 
22 
Day 
29 
Day 
36 
Day 
43 
Day 
50 
Day 
573 
Day 
64 
Day 
71 
Day 
774 
Day 
1 
Day 
15 
Day 
29 
Day 
43 
Day 
563 
B Symptoms15 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Diagnosis Confirmation, 
Stage and Baseline Disease 
Assessment and 
Documentation16 
X 
Tumor Response 
Assessment16 
X 
Tumor response assessment every 8 weeks for 12 months and then every 12 weeks 
X 
Laboratory Assessments 
ACTH 
X 
Hematology17 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum Chemistry18 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Thyroid Function19 
X 
Every 3 months 
X 
HIV, Hepatitis B and C 
X 
Coagulation20 
X 
X 
X 
Urinalysis21 
X 
X 
X 
X 
X 
Pregnancy Test22 
X 
X 
X 
X 
X 
X 
X 
Archival/Baseline Biopsy 
X 
Sample for PK 
PK samples will be collected according to Table 17. 
Serum Sample for ADA to 
CX-07225
X 
X 
X 
X 
X 
X 
Serum Sample for ADA to 
Ipilimumab26 
X 
X 

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ACTH = adrenocorticotropic hormone; ADA = anti-drug antibody; AE = adverse event; ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; 
AST = aspartate aminotransferase; BUN = blood urea nitrogen; CBC = complete blood count; CRC = colorectal cancer; CT = computed tomography; CV = cardiovascular; D/C = discontinue; 
ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EOI = end of infusion; EOS = end of study; EOT = end of treatment; GI = gastrointestinal; HCG = human chorionic 
gonadotropin; HIV = Human Immunodeficiency Virus; INR = international normalized ratio; IP = investigational product; LDH = lactate dehydrogenase; 
mCRPC = metastatic castration-resistant prostate cancer; MEL = melanoma; MRI = magnetic resonance imaging; NSCLC = non-small cell lung cancer; PD = pharmacodynamics; 
PET = positron emission tomography; PK = pharmacokinetics; PT = prothrombin time; qXwk = every X weeks; RCC = renal cell carcinoma; SGOT = serum glutamic-oxaloacetic transaminase; 
SGPT = serum glutamic-pyruvic transaminase; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone. 
1.
Cycle 1 of CX-072 plus ipilimumab combination treatment is 6 weeks, Cycle 2 of CX-072 plus ipilimumab combination treatment is 5 weeks, and Cycles 3 and beyond of CX-072 are
8 weeks.
2.
Study visits that cannot occur on the scheduled day due to unforeseen circumstances other than toxicity (e.g., 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. Visits conducted outside the windows are to be discussed with the Medical Monitor in advance.
3.
This is not a clinic visit; this is for radiologic assessment and response assessment by the Investigator prior to beginning the next treatment. These assessments should occur between -3 days
and the indicated day, and before administering the next dose of treatment.
4.
This column is intentionally left blank. There are no procedures occurring on Cycle 2 Day 77.
5.
To include confirmation of previous cancer diagnosis and recording cancer treatment history, current symptoms at baseline (defined as value at screening), and medications currently being
taken.
6.
Adverse events and concomitant medications will be assessed and reviewed prior to infusion and at any other visit that includes a physical examination. Once study drug is discontinued,
only new medications for the treatment of the patient’s cancer need to be recorded, as applicable during follow-up.
7.
If a ≥ Grade 2 infusion-related reaction is observed during or after an infusion, a local blood draw is required to measure tryptase, total immunoglobulin E, and complement C3a and C5
preferably within 2 hours and no more than 6 hours after the first signs/symptoms of the reaction.
8.
CT and/or MRI to be performed within 30 days prior to the first dose of CX-072 and repeated q8wk (Day 0 to 12 months) and then q12wk (Month 13 to 24). Scans will also be repeated at
the EOT visit and, if applicable, at the EOS visit (i.e., if the patient has not experienced progression). Methodology used should remain consistent for the duration of patient participation in
the study.
9.
Lymphoma patients only. Methodology used to evaluate lesions should remain consistent for the duration of patient participation in the study.
10.
Bone scans must be done at all visits indicated for patients with mCRPC. For patients with MEL, RCC, CRC, and NSCLC, perform bone scan at baseline (defined as value at screening) or
at response assessment visits as clinically indicated. Collect and hold scans for review by an independent committee.
11.
12-lead ECGs should be obtained in triplicate (approximately 2 to 5 minutes apart), in digital format (when possible), and archived, while supine at screening, 30 (± 15) minutes before and
after CX-072 infusion on Cycle 1 Day 1 and Cycle 2 Day 64, and again at EOT, and as clinically indicated.
12.
Physical examinations should be performed at screening and on Day 1, on each day of Probody therapeutic dosing and at the EOT visit. At all other visits, targeted physical examinations
should be performed as needed by patient symptoms or clinical observations, focused on key organ systems of interest (e.g., CV, pulmonary, GI, skin, ophthalmic, endocrine, or any systems
with previously noted abnormal findings). Dermatologic evaluations should be performed prior to initiation of therapy and every 2 months while on therapy.
13.
Vital signs include heart rate and blood pressure (supine), temperature, respiratory rate, and pulse oximetry. During the first 4 doses of combination therapy, vital signs should be measured
within 60 (± 5) minutes prior to infusion, every 15 (± 5) minutes during infusion, at the EOI (± 5 minutes), and approximately hourly for 4 hours (± 5 minutes) after the completion of
infusion. On all other infusion days, vital signs should be measured within 60 (± 5) minutes prior to infusion, at the EOI (± 5 minutes), and 60 (± 5) minutes after completion of infusion
(unless clinical signs require more frequent monitoring). Weight should be measured at screening and before each dose. Height should be measured at screening only. During an infusion
reaction, vital signs should be recorded every 2 to 5 minutes until stable.
14.
Performance status should be assessed at screening, Day 1 and prior to each subsequent infusion, Day 29, and at the EOT visit.
15.
Lymphoma patients only, B symptoms: fever, chills, fatigue, night sweats, weight loss, and pruritus.
16.
Tumor measurements will be recorded at baseline (defined as value at screening) and repeated q8wk (from Dose 1 for 12 months), then q12wk until EOT, and at the EOT visit; refer to
tumor-specific response criteria guidelines in the Common Core Document. The patient will be re-baselined at the initial/unconfirmed progression. Methodology used for tumor assessments
should remain consistent for the duration of patient participation in the study.
17.
Including CBC with differential, including blast count and platelet count pre-dose.
18.
Including alkaline phosphatase, AST/SGOT and ALT/SGPT, amylase, lipase, total bilirubin, calcium, phosphorus, BUN, creatinine, total protein, albumin, glucose, potassium, sodium,
chloride, bicarbonate, uric acid, magnesium, and LDH. Blood glucose should be fasting to evaluate possible hyperglycemia. Calculated creatinine clearance is required at screening.
Laboratory assessments drawn on the day of infusion should be drawn pre-dose.
19.
Including TSH, free T4 and T3. Thyroid function will be assessed at baseline (defined as value at Cycle 1 Day 1), every 3 months during treatment, at the discretion of the Investigator, and
at the EOT visit.

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20.
Including PT/aPTT/INR at screening, and pre-dose Day 1, at EOT visit, and as clinically indicated.
21.
Urinalysis (including assessment of protein, blood, leukocytes, glucose, ketones, bilirubin, urobilinogen, pH, and specific gravity) with microscopic examination at screening, Day 1 of each
cycle and the EOT visit.
22.
Serum pregnancy test (HCG) should be evaluated in all women of childbearing potential at screening (if 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 monthly (i.e., q4wk) while on treatment, and at EOT visit.
25.
ADA to CX-072 samples will be on Cycle 1 Day 1, Cycle 1 Day 22, Cycle 2 Day 64, Cycle 3 Day 1, Cycle 4 Day 29, and on Day 29 of every 4 cycles thereafter (e.g., Cycle 8 Day 29,
Cycle 12 Day 29, etc.) prior to each CX-072 dose, at EOT, and > 90 days following EOT.
26.
ADA to ipilimumab samples will be on Cycle 1 Day 1 and Cycle 2 Day 64 prior to the ipilimumab dose.
Patients will be followed approximately every 3 months for progression and overall survival (± 14 days) after the last dose of IP, or until withdrawal from study participation or death, whichever 
occurs first. An EOT visit will be conducted at the conclusion of treatment. The initial follow-up visit should be scheduled approximately 28 days after the patient’s last study drug administration. 
Refer to Table 16. Toxicity management may require additional visits at the discretion of the Investigator.

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Table 16: 
Schedule of Events: Follow-Up Period for Parts A
 of the Study 
Follow-Up Period 
Follow-Up 
Follow-Up 
End of Study 
(withdraw consent/death) 
+ 28 days
Every 3 months 
AE Assessment1 
X 
X 
X 
CT/MRI (chest, abdomen, pelvis) 
X 
X2 
PET/CT or PET with Diagnostic CT3 
X 
X2 
Bone Scan4 
X 
X2 
Physical Examination 
X 
Vital Signs 
X 
ECOG Performance Status 
X 
Tumor Response Assessment 
X 
X2 
X 
Hematology 
X 
Serum Chemistry 
X 
Pregnancy Test 
X5 
Survival Status 
X 
X 
X 
New Cancer Treatments6 
X 
X 
X 
1. For follow-up visits beyond 28 days post study drug, only serious study drug-related events and any late onset irAEs should be reported.
2. Patients with SD, PR, or CR will have imaging and tumor response assessment completed every 8 weeks for the first 12 months and then every 12 weeks until confirmed progression of disease.
3. Lymphoma patients only. Methodology used to evaluate lesions should remain consistent for the duration of patient participation in the study.
4. Bone scans must be done at all visits indicated for patients with mCRPC. For patients with MEL, RCC, CRC, and NSCLC, perform bone scan at baseline (defined as value at screening) or at
response assessment visits as clinically indicated. Collect and hold scans for review by an independent committee.
5. Urine or serum pregnancy test should be obtained 3 and 6 months after the EOT visit.
6. Following progression, new chemotherapy, biochemotherapy, radiation or immunotherapy or any investigational treatment for treatment of the patient’s cancer.
AE = adverse event; CT = computerized tomography; CR = complete response; CRC = colorectal cancer; ECOG = Eastern Cooperative Oncology Group; EOT = end of treatment;
irAE = immune-related AE; mCRPC = metastatic castration-resistant prostate cancer; MEL = melanoma; MRI = magnetic resonance imaging; NSCLC = non-small cell lung cancer;
PET = positron emission tomography; PR = partial response; RCC = renal cell carcinoma; SD = stable disease.

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Table 17: 
Pharmacokinetic Sampling Schedule 
Study Day 
Parts A and A2 
Parts B1 and 
B21,7 
Part C7 
Parts D 
 
Cycle 1 Day 1 
0 hr pre-dose2 
EOI3 
0 hr pre-dose2 
EOI3 
0 hr pre-dose2 
EOI3 
0 hr pre-dose 
EOI3 
Cycle 1 Day 1 
0 hr pre-dose2 
(ipi) 
EOI3 (ipi) 
Cycle 1 Day 1 
0 hr pre-dose2 
(vem) 
3 hr post-dose3,5 
(vem) 
Cycle 1 Day 2 
EOI + 24.0 hr4 
Cycle 1 Day 3 
EOI + 48.0 hr4 
Cycle 1 Day 8 
EOI + 168.0 hr4 
Cycle 1 Day 15 
0 hr pre-dose2 
0 hr pre-dose2 
EOI3 
0 hr pre-dose2 
Cycle 1 Day 22 
0 hr pre-dose2 
Cycle 1 Day 29 
0 hr pre-dose2 
0 hr pre-dose2 
EOI3 
0 hr pre-dose2 
Cycle 1 Day 29 
0 hr pre-dose2 
(vem) 
3 hr post-dose3,5 
(vem) 
Cycle 1 Day 43 
0 hr pre-dose2 
Cycle 26 Day 1 
0 hr pre-dose2 
EOI3 
0 hr pre-dose2 
EOI3 
0 hr pre-dose2 
Cycle 26 Day 29 
0 hr pre-dose2 
EOI3 
0 hr pre-dose2 
EOI3 
0 hr pre-dose2 
EOI3 
Cycle 26 Day 64 
0 hr pre-dose2 
EOI3 
Cycle 26 Day 64 
0 hr pre-dose2 
(ipi) 
EOI3 (ipi) 
Cycle 36 Day 1 
0 hr pre-dose2 
0 hr pre-dose2 
Cycle 46 Day 29 and 
every 4 cycles 
thereafter 
0 hr pre-dose2 
0 hr pre-dose2 
0 hr pre-dose2 
0 hr pre-dose2 
EOT 
At visit 
At visit 
At visit 
At visit 
Follow-Up 
At visit 
At visit 
At visit 
At visit 
1. CX-072 should be administered first, followed by a saline flush, and then the administration of
ipilimumab (no sooner than 30 minutes from completion of CX-072 infusion).

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2. All pre-dosing samples may be drawn with other study-related blood draws prior to infusion.
Vemurafenib predose samples should be collected pre-vemurafenib administration.
3. EOI samples are measured 30 minutes after EOI ± 10 minutes.
4. Sampling windows are as follows: 24 hours ± 6 hours, 48 hours ± 12 hours, 168 hours ± 24 hours.
5. Post-dose samples are measured from the time of the EOI.
6. With the exception of EOI, Cycle 2 and beyond sampling windows are ± 2 days.
7. Sample time point refers to CX-072 unless otherwise specified.
EOI = end of infusion; EOT = end of treatment; hr = hour; ipi = ipilimumab; vem = vemurafenib.
EOI: End of Infusion. All hourly times noted are measured from the end of the infusion. 
PK: Serial blood samples will be collected to characterize the single and multidose PK profile of 
CX-072 when administered alone, and CX-072, ipilimumab, and vemurafenib when
administered in combination.
 
 
  
 
 
 
 

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16.
ADVERSE EVENTS
16.1. 
Adverse Event Definitions
16.1.1. 
Adverse Event 
An AE is defined as any untoward medical occurrence in a clinical investigation patient 
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 
IP, whether or not related to the IP. All AEs, including observed or volunteered problems, 
complaints, or symptoms, are to be recorded on the appropriate eCRF. 
All AEs related to mandated protocol interventions (i.e., screening biopsies) should also be 
recorded in the eCRF as an AE. 
Progressive disease in and of itself, as well as signs and/or symptoms associated with disease 
progression, is not considered an adverse event or SAE. Progressive disease is an efficacy 
finding and should not be reported unless the progressive disease results in death during the 
reporting period. Deaths, reported as SAEs due to progressive disease and considered not related 
to study drug, will be excluded from treatment-emergent AE analysis.  
16.1.2. 
Suspected Adverse Reaction 
A suspected adverse reaction (SAR) 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). 
16.1.3. 
Life-Threatening Adverse Event or Life-Threatening Suspected Adverse 
Reaction 
An AE or SAR is considered “life-threatening” if, in the view of either the Investigator or 
Sponsor, its occurrence places the patient at immediate risk of death. It does not include an AE 
or SAR that, had it occurred in a more severe form, might have caused death. 
16.1.4. 
Serious Adverse Event or Serious Suspected Adverse Reaction 
An AE or SAR 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, or
•
A congenital anomaly/birth defect.

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Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, they 
may jeopardize the patient or may require medical or surgical intervention to prevent 1 of the 
outcomes listed in this definition. Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
16.1.5. 
Unexpected Adverse Event or Unexpected Suspected Adverse Reaction 
An AE or SAR is considered “unexpected”: 
•
If it is not listed in the Reference Safety Information of the Investigator’s Brochure or is
not listed at the specificity or severity that has been observed; or
•
If an Investigator’s Brochure is not required or available, the event 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 Investigator’s Brochure referred only to elevated hepatic enzymes or hepatitis. 
Similarly, cerebral thromboembolism and cerebral vasculitis would be unexpected (by virtue of 
greater specificity) if the Investigator’s Brochure listed only cerebral vascular accidents.  
“Unexpected,” as used in this definition, also refers to AEs or SARs that are mentioned in the 
Investigator’s Brochure 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. 
For marketed products, expectedness assessment for all regions will be performed using the 
Summary of Product Characteristics per the European Medicines Agency website: 
www.ema.europa.eu for Yervoy and Zelboraf. 
16.2. 
Adverse Event Classification 
16.2.1. 
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 IP caused or contributed to an AE. The relationship to IP will be 
categorized as “Yes” or “No.” 
16.2.2. 
Severity 
The severity of an event describes the degree of impact upon the patient and/or the need for, and 
extent of, medical care necessary to treat the event. 
Adverse event 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 18 will be used to describe 
the maximum intensity of the AE. 

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Table 18: 
Adverse Event Severity 
Grade 
Description 
Grade 1 
Awareness of sign or symptom, but easily tolerated 
Grade 2 
Discomfort enough to cause interference with normal daily activities 
Grade 3 
Inability to perform normal daily activities 
Grade 4 
Life-threatening consequences; urgent intervention required 
Grade 5 
Death related to AE 
16.3. 
Exposure in Utero 
The patient will be instructed to notify the Investigator if the patient or patient’s partner becomes 
pregnant during the study or within 60 days (105 days for patients enrolled in the UK) after the 
last dose of study drug. The Investigator must notify the Sponsor within 24 hours via the 
Pregnancy Notification Form and submit it to the Sponsor. The Investigator should obtain 
informed consent/assent from the patient or patient’s partner allowing the Investigator to obtain 
information regarding the pregnancy and its outcome. If the patient or patient’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. 
If the outcome of the pregnancy meets criteria for immediate classification as an SAE (e.g. 
spontaneous abortion, birth defect born to a patient or patient’s partner exposed to study drug), 
the investigator should follow the procedures for reporting an SAE. 
16.4. 
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 adverse events and up to and including 90 days after 
administration of the last dose of study drug for all immune-related adverse events) 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, US FDA, and other regulatory agencies regarding any DLTs 
or other AEs of interest. 
For SAEs, the Investigator must record the SAE information in the electronic data capture (EDC) 
system with as much information as possible and submit it within the time frame described in 
Section 16.6. When additional information is received (e.g. the outcome of an event is known), 
the Investigator should record the updated information in the EDC system. If the patient was 
hospitalized, a copy of the discharge summary and any other relevant hospital records (e.g., 
admission report, laboratory test results, etc.) should be included as part of the patient’s medical 
file.  

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All AEs considered to be related (definitely, probably, or possibly related) to study drug and all 
SAEs will be followed until resolved or until a stable status has been achieved. The type of 
follow-up (e.g., phone, site visit, etc.) will be left to the discretion of the Investigator. 
16.5. 
Documentation of Adverse Events by Investigator 
Patients will be evaluated and questioned generally to identify AEs during the course of the 
study. Events occurring after the ICF has been signed and prior to administration of the first 
dose, except AEs related to mandated protocol interventions, will be recorded on the Medical 
History eCRF. Events occurring after administration of the first dose of study drug and events 
related to mandated protocol interventions, including those occurring prior to administration of 
the IP, will be recorded on the AE eCRF. AEs that occur up to and including 30 days after 
administration of the last dose of study drug and AEs that occur up to and including 90 days after 
administration of the last dose of study drug for irAEs must be reported in the EDC system. 
All AEs spontaneously reported by the patient 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 AE 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 
AE 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, 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 patient
participation in the clinical research study; and/or
•
The test finding is considered clinically significant by the Investigator based on his/her
medical judgment. If an abnormal laboratory value is recorded as an AE then the
corresponding laboratory value must be marked as clinically significant in the database.
Similarly, if an abnormal laboratory value is marked as clinically significant in the
database it should be recorded as an AE.
When 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 and 
the Common Core Document (APPENDIX 1). Clinical syndromes associated with laboratory 
abnormalities are to be recorded as appropriate (e.g., diabetes mellitus rather than 
hyperglycemia).  

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16.6. 
Notification About Serious Adverse Events and Suspected 
Unexpected Serious Adverse Reactions 
16.6.1. 
Investigator Reporting to Sponsor 
All SAEs that occur after the ICF has been signed must be reported to the Sponsor 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 
after administration of the last dose of study drug (up to and including 90 days after the last dose 
of CX-072 for serious irAEs) must be reported to the Sponsor within 24 hours from when the 
Investigator becomes aware of the SAE. Please refer to Section 16.3 regarding reporting of SAEs 
associated with pregnancies.  
To report the SAE, the Investigator must record the SAE information on the AE eCRF and other 
relevant eCRFs electronically in the EDC system for the study. When the form is completed, 
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 CytomX Safety 
at safety@cytomx.com, and fax the completed paper SAE form CytomX within 24 hours of 
awareness. A CytomX eFax number will be provided by Administrative Letter after the filing of 
Amendment 09. When the EDC system becomes available, the SAE information must be entered 
within 24 hours of the system becoming available.  
Investigators must report to the Sponsor any SAE, whether or not considered drug-related, 
including those listed in the protocol module or Investigator’s Brochure. 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 AE eCRF. 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 patient death, a death certificate and summary of available autopsy findings (as 
applicable) must be submitted as soon as possible to the Sponsor or its designated representative. 
16.6.2. 
Serious Adverse Events Follow-Up 
The Investigator must continue to follow the patient until the SAE has subsided or until the 
condition becomes chronic in nature, the condition stabilizes (in the case of persistent 
impairment), the patient withdraws consent, the patient is lost to follow-up, the patient dies, or it 
has been assessed that the study treatment/procedure is not the cause of the AE. 
Within 24 hours of receipt of follow-up information, the Investigator must update the SAE 
information electronically in the EDC system for the study and submit any supporting 
documentation (e.g., patient discharge summary or autopsy reports) to CytomX 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.

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16.6.3. 
Reporting to Regulatory Agencies and Institutional Review Board/Independent 
Ethics Committee 
The Sponsor will report all relevant information about suspected unexpected serious adverse 
reactions (SUSARs) that are fatal or life-threatening to the FDA as applicable, applicable 
competent authorities in all the Member States concerned, and the Central Institutional Review 
Board (IRB)/Independent Ethics Committee (IEC), as soon as possible, and in any case no later 
than 7 days after initial knowledge by the Sponsor of such a case, which may include a final 
SUSAR report 8 days after the initial 7-day notification.  
All other SUSARs will be reported to the FDA as applicable, applicable competent authorities in 
all the Member States concerned, 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 also inform all Investigators as required with instructions to submit to local 
IRB/IECs per local requirements. 
16.7. 
Rapid Notification of Events of Special Interest 
In addition to SAEs, the following AESI will be reported to the Sponsor or its designee within 
24 hours of site awareness irrespective of seriousness, severity, or causality: 
•
Any potential Hy’s Law case (> 3 × ULN of either ALT/AST with concurrent > 2 × ULN
of total bilirubin and lack of alternate etiology)
•
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:
o
Pneumonitis
o
Colitis
o
Hepatitis (including AST or ALT elevations > 3 × ULN or bilirubin > 1.5 × ULN)
o
Nephritis (including serum creatinine > 1.5 × ULN)
o
Pancreatitis
o
Motor and sensory neuropathy
o
Myocarditis
o
Encephalitis
o
Endocrinopathies (including but not limited to hypothyroidism, hyperthyroidism,
hypophysitis, diabetes mellitus, and adrenal insufficiency)
o
Ocular toxicities (eg, uveitis)
o
Skin reactions including Stevens-Johnson syndrome or toxic epidermal
necrolysis, and
o
Diarrhea

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Refer to Section 16.6 and the Common Core (APPENDIX 1) for reporting SAEs, DLTs, and 
AESI. 
16.8. 
Module Specified Events 
16.8.1. 
Module Specified Serious Adverse Events 
Grade 3 and 4 AEs and their consequences will not be reported as SAEs in an expedited manner 
if attributable to underlying disease status or progression. 
16.8.2. 
Module Specified Adverse Events 
Patients 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 (e.g., transfusions, delay in study drug administration) should be 
reported as AEs. 
Progression of disease (including the major signs and symptoms of disease progression) is a 
study endpoint and should not be reported as an AE/SAE. However, when a patient dies from 
any cause, including disease progression, the death should be reported as an SAE. 
CX-072
There have been no clinical studies conducted to date with CX-072. Reported serious events of 
special interest with other PD-1/PD-L1 agents include irAEs of pneumonitis; colitis; hepatitis; 
and endocrinopathies of the thyroid, adrenal gland, and pituitary gland. Reported immune-related 
adverse reactions with other PD-1/PD-L1 agents include meningoencephalitis, myasthenic 
syndrome/myasthenia gravis, Guillain-Barré syndrome, ocular inflammatory toxicity, and 
pancreatitis, including increases in serum amylase and lipase levels. Severe infections, including 
sepsis, herpes encephalitis, and mycobacterial infection have been reported. In addition, Grade 3 
and 4 infusion reactions requiring discontinuation of study drug have also been reported. 
Refer to the Investigator’s Brochure for a summary of nonclinical toxicology information. 
Ipilimumab 
•
Refer to the current package insert for ipilimumab (Yervoy US Package Insert, 2015) for
common adverse reactions, black box warnings, and other information pertaining to the
management of AEs associated with ipilimumab treatment.
•
Most common adverse reactions (≥ 5%) are fatigue, diarrhea, pruritus, rash, and colitis.

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BLACK BOX WARNING: Can result in severe and fatal immune-mediated adverse 
reactions due to T-cell activation and proliferation. These immune-mediated reactions 
may involve any organ system; however, the most common severe immune-mediated 
adverse reactions are enterocolitis, hepatitis, dermatitis (including toxic epidermal 
necrolysis), neuropathy, and endocrinopathy. The majority of these immune-mediated 
reactions initially manifested during treatment; however, a minority occurred weeks to 
months after discontinuation of ipilimumab.  
Permanently discontinue ipilimumab and initiate systemic high-dose corticosteroid 
therapy for severe immune-mediated reactions.  
Assess patients for signs and symptoms of enterocolitis, dermatitis, neuropathy, and 
endocrinopathy and evaluate clinical chemistries, including liver function tests and 
thyroid function tests at baseline and before each dose.  
Vemurafenib 
•
Most common adverse reactions (≥ 30%) are arthralgia, rash, alopecia, fatigue,
photosensitivity reaction, nausea, pruritus, and skin papilloma.
•
New primary malignancies:
−
cSCC, keratoacanthoma, and melanoma were observed at a higher incidence in
patients receiving vemurafenib compared with patients in the control arm.
Dermatologic evaluations prior to initiation of therapy and every 2 months while
on therapy should be performed. Dermatologic monitoring for 6 months following
discontinuation of vemurafenib should be considered.
•
Hypersensitivity reactions: Anaphylaxis and other serious hypersensitivity reactions
during treatment and re-initiation of treatment (generalized rash and erythema,
hypotension, and drug reaction with eosinophilia and systemic symptoms [DRESS
syndrome]). Permanently discontinue vemurafenib in patients who experience a severe
hypersensitivity reaction.
•
Dermatologic reactions: Permanently discontinue vemurafenib in patients who
experience a severe dermatologic reaction (e.g., Stevens-Johnson syndrome and toxic
epidermal necrolysis).
•
QT prolongation: Do not start treatment in patients with uncorrectable electrolyte
abnormalities, QTc ≥ 500 ms, or long QT syndrome, or in patients who are taking
medicinal products known to prolong the QT interval. Prior to and following treatment
initiation or after dose modification for QTc prolongation, evaluate ECG and electrolytes
(including potassium, magnesium, and calcium) after 15 days, monthly during the first
3 months, and then every 3 months thereafter or more often as clinically indicated. See
other recommendations in prescribing information (Zelboraf US Package Insert, 2017).
•
Hepatotoxicity: Liver injury leading to functional hepatic impairment, including
coagulopathy or other organ dysfunction – monitor transaminases, alkaline phosphatase,
and bilirubin before initiation of treatment and monthly during treatment, or as clinically
indicated. Manage laboratory abnormalities with dose reduction, treatment interruption,
or treatment discontinuation.

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•
Photosensitivity: Advise patients to avoid sun exposure, wear protective clothing, and
use a broad-spectrum ultraviolet A/ultraviolet B sunscreen and lip balm (sun protection
factor ≥ 30) when outdoors.
•
Ophthalmologic reactions: Uveitis, blurry vision, and photophobia can occur in patients
treated with vemurafenib.
•
Radiation sensitization and radiation recall: These effects are possible in patients
treated with radiation prior to, during, or subsequent to vemurafenib treatment.
16.9. 
Emergency Identification of Study Medication 
Study CTMX-M-072-001 is open label. Emergency identification of study medication does not 
apply. 

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17.
ETHICS
17.1. 
Institutional Review Board or Independent Ethics Committee
The IRB/IEC will meet all FDA requirements governing IRBs (21 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): protocol, ICF, 
and any other relevant materials intended for or directed to patients (e.g., patient 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. 
17.2. 
Ethical Conduct of the Study 
This study will be conducted in accordance with the current IRB/IEC approved clinical protocol, 
International Conference on Harmonisation 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. 
17.3. 
Patient Information and Informed Consent 
Written informed consent/assent is required from each patient prior to any testing under this 
protocol, including screening tests and evaluations. The ICF, as specified by the clinical site’s 
IRB/IEC, must follow the Protection of Human Patients 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 patient will be entered into the study. The ICF will contain a statement that the 
consent is freely given, that the patient is aware of the risks and benefits of entering the study, 
and that the patient is free to withdraw from the study at any time. Written informed consent 
must be given by the patient after the receipt of detailed information on the study. It is the 
responsibility of the Investigator to obtain consent/assent and to provide the patient with a copy 
of the signed and dated ICF. Confirmation of a patient’s informed consent must also be 
documented in the patient’s medical record prior to any testing under this protocol, 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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18.
STUDY ADMINISTRATION
18.1. 
Common Core Document Amendments
Changes to the conduct of the study should be prepared as an amendment to the Common Core 
Document or a module amendment and implemented only upon approval of the Sponsor or a 
representative of the Sponsor. Protocol amendments should also receive written IRB/IEC 
approval and, where appropriate, Competent Regulatory Authority approval prior to 
implementation, except when necessary to eliminate immediate hazards to the patients or when 
the changes involve only logistical or administrative aspects of the trial (e.g., change of monitor, 
telephone numbers). In this case, the Sponsor will amend and implement the protocol change and 
subsequently notify the regulatory authorities and/or the IRB/IEC, as appropriate. 
18.2. 
Module Amendments 
Changes to the conduct of the study will be prepared by the Sponsor as an amendment to the 
Module and/or the Clinical Core Protocol 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 and, where appropriate, Competent Regulatory Authority 
approval prior to implementation, except when necessary to eliminate immediate hazards to the 
patients or when the changes involve only logistical or administrative aspects of the trial (e.g., 
change of monitor, telephone numbers). In this case, the Sponsor will amend and implement the 
protocol change and subsequently notify the regulatory authorities and/or the IRB/IEC, as 
appropriate. 

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19.
LONG-TERM EXTENSION INTRODUCTION
19.1. 
Long-term Extension Rationale
Study CTMX-M-072-001 as described in Section 4 through Section 18 was the first clinical 
study under which CX-072 was studied in humans. The long-term extension part of Study 
CTMX-M-072-001 as described in Section 19 through Section 27 is an extension of the study for 
patients previously enrolled in the parent study CTMX-M-072-001 who remain active on CX-
072 treatment and wish to continue therapy with CX-072. Patients who are receiving study 
treatment with CX-072 monotherapy, and who continue to derive clinical benefit without 
unacceptable toxicity as determined by the Investigator, will be eligible to enroll in the long-term 
extension. Patients will be provided CX-072 treatment for a maximum of 12 months as 
calculated from the initiation of treatment in the long-term extension and will be followed to 
assess long-term safety of CX-072.  

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20.
LONG-TERM EXTENSION OBJECTIVE
20.1. 
Primary Objective
The primary objective of the long-term extension is to maintain CX-072 treatment for patients 
experiencing ongoing clinical benefit and to assess long-term safety of CX-072 monotherapy. 
20.2. 
Long-term Extension Study Design 
The long-term extension provides continued access to CX-072 monotherapy and evaluates the 
long-term safety of CX-072 in patients with solid tumor malignancies who have previously 
participated in the parent study CTMX-M-072-001. 
Patients from Study CTMX-M-072-001 are eligible to enroll in the long-term extension if they 
are actively receiving CX-072 monotherapy and will continue to benefit from treatment with 
CX-072 monotherapy as determined by the Investigator.
Eligible patients must sign a new informed consent for this study.
For the long-term extension, a CX-072 monotherapy treatment cycle will consist of 14 days.
Figure 9: 
Long-Term Extension Study Schema 
CTMX-M-072-001 
(parent study) 
CTMX-M-072-001 Long-term Extension  
Treatment at patient’s last dose regimen as in parent study 
Screening/eligibility assessment 
12 months after start of long-term extension, 
disease progression, or unacceptable toxicity 
Treatment permanently discontinued 
Safety follow-up  
SAEs (30 days) and serious irAEs (90 days) 

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21.
LONG-TERM EXTENSION STUDY ELIGIBILITY CRITERIA
21.1. 
Inclusion Criteria
1. Previously enrolled in Study CTMX-M-072-001 Parts A-E for at least 12 months (as
calculated from the patient’s prior Cycle 1, Day 1 to the first infusion administered in the
long-term extension
2. Actively receiving CX-072 monotherapy; patients must be assessed by the Investigator as
still receiving clinical benefit from CX-072 in Study CTMX-M-072-001 without
unacceptable toxicity
3. Demonstrated compliance as assessed by the Investigator during Study CTMX-M-072-
001
4. Women of childbearing potential and males must agree to use a highly effective method
of contraception (details provided in APPENDIX 5) prior to study entry, while taking
study drug, and for a period of 105 days following the last treatment
5. Written informed consent must be obtained prior to enrolling in the long-term extension
21.2. 
Exclusion Criteria 
1. Illness or medical condition which in the opinion of the investigator could compromise
the patient’s safety at enrollment
2. Prohibited concomitant therapy outlined in the protocol
3. Concurrent participation in another therapeutic clinical trial

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22.
LONG-TERM EXTENSION ENROLLMENT AND STUDY
PROCEDURES
22.1. 
Informed Consent 
Patients must sign a new informed consent form for the long-term extension before receiving the 
first dose of CX-072 under Protocol Amendment 09.  
22.2. 
Enrollment 
Patients will be enrolled using an interactive web response system (IWRS). The investigative site 
will log into the IWRS to enroll a patient who meets eligibility criteria for the long-term 
extension. Each patient enrolled in the long-term extension will receive a unique patient number 
upon enrollment. Individual patient data from the parent study and this current long-term 
extension will be linked by another unique identifier. An individual patient will have the same 
unique identifier across both study parts (parent study and long-term extension). Once assigned, 
numbers will not be re-used. Study treatment must commence within 7 days after enrollment but 
not earlier than 14 days from previous dose received in parent CTMX-072-001 study. At each 
medical center, patients must be approached for informed consent to enter the long-term 
extension at their next clinic visit following the approval of Protocol Amendment 09. 
22.3. 
CX-072 Dispensation 
CX-072 will be dispensed by the study site personnel to patients at scheduled study visits.
22.4. 
Safety Assessment 
Safety assessments will be performed at all visits to the site throughout study treatment per 
disease-specific standard of care.  
Assessments such as physical examination, vital signs, and patient weight will be performed at 
each study visit per standard of care. Significant signs and symptoms will be monitored 
throughout the study. Electrocardiogram should be performed if clinically necessary. 
22.5. 
Tumor Imaging 
Assessment for tumor response and disease progression should be conducted according to 
standard of care, including the frequency and modality of imaging. The decision to continue 
study drug(s) beyond initial investigator-assessed progression must be agreed upon by the 
Sponsor Medical Monitor and documented in the study records. 
22.6. 
Laboratory Assessments 
Laboratory assessments should be performed per standard of care for anti-PD-1/PD-L1 therapy, 
including complete blood counts with differential, chemistry panel, thyroid function tests, and 
pregnancy tests. 
For the long-term extension, PK, ADA, and exploratory blood sampling will be discontinued. 

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22.7. 
End of Treatment 
The reason and date for discontinuation from treatment will be recorded on the eCRF. 

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Table 19: 
Schedule of Events for Long-term Extension 
Period/Procedure 
Treatment Period 
Screening Period 
Cycles 1 - n 
± 2 days of scheduled visit 
EOT9 
Study/Visit Day1
-7 to 0
Day 1 
Informed Consent and confirmation 
of participation in prior protocol 
X 
AE Assessment2  
X 
X 
Study Drug Administration 
CX-072 Infusion3
X 
Imaging 
CT/MRI 4 
Per institution standard of care 
Laboratory Assessments 
Hematology5 
Per institution standard of care 
Serum Chemistry6 
Per institution standard of care 
Thyroid Function7 
Per institution standard of care 
Pregnancy Test8 
Per institution standard of care 
Per institution standard of care 
Note:  A treatment cycle consists of 14 days. AE = adverse event; CT = computed tomography; MRI = magnetic resonance imaging; T4 = thyroxine; TSH = thyroid-stimulating 
hormone. 
1.
Study visits that cannot occur on the scheduled day due to unforeseen circumstances other than toxicity should be completed as close to the scheduled date as possible.
2.
All AEs will be assessed and reviewed prior to infusion during study visit. SAEs are to be reported up to and including 30 days after the last dose of CX-072 and up to
and including 90 days after last dose of CX-072 for serious irAEs.
3.
Patients shall continue the same dose of CX-072 that they last received in the previous cohort (Parts A-E) of the study that they were enrolled in. No dose increase or
decrease of CX-072 is permitted in long-term extension.
4.
CT and/or MRI should be repeated per institutional standard of care.
5.
CBC with differential for long-term extension should be performed at the frequency per institution standard of care for anti-PD-1/PD-L1 therapy.
6.
Chemistry testing for long-term extension should be performed per institution standard of care for anti-PD-1/PD-L1 therapy.
7.
TSH and free T4 for long-term extension should be performed at the frequency per institution standard of care for anti-PD-1/PD-L1 therapy.
8.
Urine pregnancy test (with serum test as needed for confirmation) should be obtained for long-term extension at the frequency per institution standard of care for anti-
PD-1/PD-L1 therapy. Pregnancies in the patient or patient’s partner within 60 days (105 days in the UK) after the last dose are to be reported to the Sponsor within 24
hours via the Pregnancy Notification Form.
9.
An EOT visit will be conducted at the conclusion of treatment or within 7 days of the last dose. Once a patient has met a withdrawal criterion for study drug treatment,
participation in this study will only occur for safety purposes. Survival follow-up will no longer occur.

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22.8. 
Follow-Up Phase 
The follow-up phase will only comprise safety follow-up for 30 days after the last dose of study 
drug to report SAEs and 90 days for serious irAEs that may have occurred after the patient 
discontinued study treatment. All SAEs including serious irAEs will be followed until resolution 
or until the Investigator declares the toxicity is stable. Survival information will not be collected 
following the last dose of study drug. 

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23.
LONG-TERM EXTENSION STUDY TREATMENT
See Section 11 for CX-072 packaging, labeling, handling, storage, accountability, and disposal 
information. 
Dosage and Administration 
For the long-term extension, a patient may receive up to 12 months of therapy, calculated from 
the first infusion date administered under Protocol Amendment 09. This length of time was 
determined with the understanding that all patients enrolled into this extension protocol would 
have had the opportunity to receive a minimum of 2 years in total of treatment with this 
investigational agent.   
In the long-term extension, the dose and schedule of CX-072 will be the same as the last 
administered dose and schedule in the parent study CTMX-M-072-001. For example, if the 
patient was last treated with CX-072 10 mg/kg in the parent study cohort, then the dose of 
CX-072 will continue at 10 mg/kg every 2 weeks in the long-term extension. The dose of
CX-072 shall not be increased or decreased at the time of enrollment in the long-term extension.
23.1. 
Dose Interruption and Modification 
Every effort should be made to administer the study drug(s) according to the planned dose and 
schedule. There must be a minimum of 14 days between study drug infusions. Therapy with 
CX-072 in the long-term extension may continue for up to 12 months year for each patient, with
the rationale previously stated above in Section 19.1.
In the long-term extension, an infusion may be delayed for up to 14 days. A patient must 
discontinue study drug if he/she cannot safely receive an infusion of CX-072 for 84 days, 
calculated from the last treatment date. If a patient is receiving corticosteroids on a taper, the 
daily dose of prednisone must be < 10 mg/day (or its equivalent) for an infusion to be 
administered.
23.2. 
Management of Infusion Reactions 
See Section 11.6 for management of infusion reactions. 

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24.
DSMB MONITORING
There will be no DSMB monitoring in the long-term extension study. 

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25.
LONG-TERM EXTENSION STUDY
25.1.1. 
Prior Therapy 
Patient’s prior therapy captured in the parent study CTMX-M-072-001 will not be collected 
again in the long-term extension. 
25.1.2. 
Prohibited Medications 
Patients should not receive other anticancer therapy (cytotoxic, biologic, or hormone other than 
for replacement), live vaccines, or experimental therapy while on treatment in this study. The use 
of herbal medication should be discouraged per standard of care.  

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26.
LONG-TERM EXTENSION STUDY SAFETY MONITORING
AND REPORTING
See Section 16 for AE definitions, classification, exposure in utero, monitoring, and 
documentation. 
26.1. 
Adverse Event Reporting for the Long-Term Extension 
All AEs including possible cases of Hy’s Law or immune-related AEs (as described in 
Section 16.7) will be collected in the long-term extension. SAEs are reportable through 30 days 
after the last dose of study drug and through 90 days after administration of the last dose of study 
drug for serious irAEs (see Section 16.6 and Section 16.7). 

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27.
LONG-TERM EXTENSION STATISTICAL CONSIDERATIONS
Details of the statistical analyses will be included in a separate long-term extension Statistical 
Analysis Plan (SAP). 

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28.
REFERENCES
P450 Drug Interaction Table. Indiana University: Department of Medicine; 2015. Cited 
2016 Aug 01. Available from: http://medicine.iupui.edu/clinpharm/ddis/main-table/.  
Adams S, Loi S, Toppmeyer D, Cescon DW, De Laurentiis M, et al. Phase 2 study of 
pembrolizumab as first-line therapy for PD-L1–positive metastatic triple-negative breast cancer 
(mTNBC): Preliminary data from KEYNOTE-086 cohort B. J Clin Oncol 35, 2017 (suppl; 
abstr 1088). 
Adams S, Schmid P, Rugo HS, Winer EP, Loirat D, et al. Phase 2 study of pembrolizumab 
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29.
APPENDICES

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APPENDIX 2. 
THYMIC EPITHELIAL TUMOR CLASSIFICATION 
AND STAGING 
2015 World Health Organization Classification of Thymic Epithelial Tumors 
Tumor Type 
Tumor Characteristics 
Thymoma Type A 
Occurrence of bland, spindle shaped epithelial cells (at least focally); paucity1 of absence 
of immature (TdT+) T-cells throughout the tumor. 
Thymoma Type A/B 
Occurrence of bland, spindle shaped epithelial cells (at least focally); abundance of 
immature (TdT+) T-cells focally or throughout tumor. 
Thymoma Type B1 
Thymus-like architecture and cytology; abundance of immature T-cells; area of 
medullary differentiation (medullary islands); paucity of polygonal or dendritic epithelia 
cells without clustering (e.g., < 3 contiguous epithelial cells). 
Thymoma Type B2 
Increased number of single or clustered polygonal or dendritic epithelial cells 
intermingled with abundant immature T-cells. 
Thymoma Type B3 
Sheets of polygonal slightly moderately atypical epithelial cells; absent or rare 
intercellular bridges; paucity or absence of intermingled TdT+ T-cells. 
Thymic Carcinoma 
Lacks immature T-cell lymphocytes present in thymomas. 
1. Paucity versus abundance: any area of crowded immature T-cells or moderate number of immature T-cells in > 10% of the
investigated tumor are indicative of “abundance.”
TdT+ = terminal deoxynucleotidyl transferase positive. 
Adapted from Marx A, Chan JK, Coindre JM, Detterbeck F, Girard N, et al. The 2015 World Health Organization 
classification of tumors of the thymus: continuity and changes. J Thorac Oncol. 2015 Oct;10(10):1383-1395. PubMed 
PMID: 26295375. 
Masaoka-Koga Staging of Advanced Thymic Epithelial Tumors 
Stage 
Criteria 
II 
Microscopic transcapsular invasion or macroscopic invasion into thymic or surrounding fatty 
tissue, or grossly adherent to but not breaking through mediastinal pleura or pericardium. 
III 
Macroscopic invasion of neighboring organs (i.e., pericardium, great vessel, or lung). 
IVA 
Pleural or pericardial dissemination. 
IVB 
Lymphatic or hematogenous dissemination. 
Koga K, Matsuno Y, Noguchi M, Mukai K, Asamura H, et al. A review of 79 thymomas: Modification of staging system and 
reappraisal of conventional division into invasive and non-invasive thymoma. Pathol Int. 1994 May;44(5):359-367. 
PubMed PMID: 8044305.  

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APPENDIX 3. 
DATA SAFETY MONITORING BOARD 
A Data 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 protocol amendments. The DSMB will be charged with 
responsibility to advise CytomX with regard to: 
1. The continuing safety of current and future participants in the study, and
2. The continuing validity and scientific merit of the study.
For Parts A
 of this study, the DSMB will convene at least 2 times per year in accordance with 
meetings scheduled to review the overall CX-072 program; more frequent 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. The 
DSMB will review all available information to determine whether the study will continue 
unchanged or whether protocol modifications are required to ensure patient safety. 
Recommendations for closing should be on the basis of excessive toxicity in the statistics report 
or the aggregated safety data or lack of efficacy. 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 the Sponsor. 
The DSMB will consist of at least 3 members. DSMB 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 will appoint additional members. Upon first site activation of 
Protocol Amendment 09 (with the transition to long-term extension), the responsibilities of the 
DSMB for this trial will end. 

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APPENDIX 4. 
SAFETY REVIEW COMMITTEE 
For Parts A-E of this study, 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: 
1. Approve dose escalation to the next cohort in each part of the study;
2. Recommend modifications to the dose or schedule as it pertains to patient safety;
3. Recommend modifications to the protocol related to patient oversight (e.g., additional
safety monitoring, changes to inclusion/exclusion criteria); or
4. Evaluate combination schedules to recommend modifications to the combination dosing
schedule/regimen.
Actions taken regarding dose escalation or amendments to the protocol will be documented and 
stored in the trial master file for the study. An SRC will not be convened for the long-term 
extension.  

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APPENDIX 5. CONTRACEPTION GUIDELINES 
The Clinical Trial Facilitation Group (CTFG) recommendations related to contraception and 
pregnancy testing in clinical trials include the use of highly effective forms of birth control. 
These methods include the following: 
•
Combined (estrogen and progestogen containing) hormonal contraception associated with
the inhibition of ovulation;
o
Oral, intravaginal, or transdermal;
•
Progestogen-only hormonal contraception associated with the inhibition of ovulation;
o
Oral, injectable, or implantable;
•
An intrauterine device;
•
Intrauterine hormone-releasing system;
•
Bilateral tubal occlusion;
•
Vasectomized partner; and
•
Sexual abstinence (defined as refraining from heterosexual intercourse during the entire
period of risk associated with the study treatment). Total sexual abstinence should only
be used as a contraceptive method if it is in line with the patients’ usual and preferred
lifestyle. Periodic abstinence (e.g., calendar, ovulation, symptothermal, and
post-ovulation methods), declaration of abstinence for the duration of exposure to study
drug, and withdrawal are not acceptable methods of contraception.
Of note, barrier contraception (including male and female condoms with or without spermicide) 
is not considered a highly effective method of contraception, and if used, this method must be 
used in combination with another acceptable method listed above. 
Definition of childbearing potential: 
Childbearing potential is defined as being physiologically capable of becoming pregnant. No 
childbearing potential is defined as one or both of the following criteria: 
•
Surgically sterile (bilateral salpingectomy, bilateral oophorectomy, or hysterectomy);
and/or
•
Post-menopausal, defined as:
o
≥ 55 years of age with no spontaneous menses for ≥ 12 months, OR
o
< 55 years of age with no spontaneous menses for ≥ 12 months AND with a
post-menopausal follicle-stimulating concentration > 30 IU/mL.
Source: Clinical Trial Facilitation Group (CTFG) (2014). Recommendations related to 
contraception and pregnancy testing in clinical trials. 
http://www.hma.eu/fileadmin/dateien/Human_Medicines/ 
01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf. Accessed
June 22, 2018.