A Phase 1a/1b Study of FPA150, an Anti-B7-H4 Antibody, in Patients With Advanced Solid Tumors
Phase: EARLY_PHASE1
Conditions: Breast Cancer, Ovarian Cancer, Endometrial Cancer, Advanced Solid Tumors
Sponsor: Five Prime Therapeutics, Inc.

 
 
 
Five Prime Therapeutics, Inc. 
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Confidential 
A Phase 1a/1b Study of FPA150, an Anti-B7-H4 Antibody, 
in Patients with Advanced Solid Tumors  
 
 
Protocol Number: 
FPA150-001 
Investigational Product: 
FPA150 
IND Number: 
136997 
EudraCT Number 
Not applicable 
Development Phase: 
Phase 1a/1b 
Indication Studied: 
Advanced Solid Tumors 
Protocol Version: 
Amendment 2  
Date of Protocol: 
04 February 2019 
Sponsor: 
Five Prime Therapeutics, Inc. 
111 Oyster Point Boulevard 
South San Francisco, CA 94080-7047 
Phone: 415-365-5600  
Responsible Medical Officer: 
, MD, MS 
Director, Clinical Development 
Five Prime Therapeutics, Inc. 
 
Confidential 
This document contains proprietary and confidential information of Five Prime Therapeutics, Inc. and may not 
be reproduced or disclosed in whole or in part without written authorization from Five Prime Therapeutics, Inc.  
 
 

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Declaration of the Investigator 
A Phase 1a/1b Study of FPA150, an Anti-B7-H4 Antibody, in Patients with 
Advanced Solid Tumors  
All documentation for this study that is supplied to me and that has not been previously 
published will be kept in the strictest confidence. This documentation includes this study 
protocol, Investigator’s Brochure (IB), electronic case report forms (eCRFs), and other 
scientific data. 
The study will not be commenced without the prior written approval of a properly constituted 
Institutional Review Board (IRB) or Independent Ethics Committee (IEC). No changes will be 
made to the study protocol without the prior written approval of the Sponsor and the IRB or 
IEC, except as necessary to eliminate an immediate hazard to the patients. 
I confirm that I have read the above-mentioned protocol/protocol amendments and its 
attachments. I agree to conduct the described trial in compliance with all stipulations of the 
protocol, applicable laws, regulations and ICH E6 Guideline for GCP. 
 
 
 
 
Principal Investigator’s Signature 
 
Date 
 
 
 
Name (printed) 
 
 
 
 
 
Institution or Company Name 
 
 
 
 

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Document History 
Document 
Date 
Amendment 2 
04 February 2019 
Amendment 1 
23 January 2018 
Original Protocol 
31 October 2017 
 
 
 

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1 
Protocol Synopsis  
Title: A Phase 1a/1b Study of FPA150, an Anti-B7-H4 Antibody, in Patients with Advanced 
Solid Tumors  
Protocol Number: FPA150-001 
Clinical Phase: 1a/1b 
Study Centers: There will be approximately 6 to 10 study centers participating in Phase 1a 
and approximately 35 study centers participating in Phase 1b.  Phase 1a (including the 
pembrolizumb combination cohort) and the combination cohorts in Phase 1b will be 
conducted in the United States only.  Phase 1b monotherapy will be conducted globally. 
Objectives and Endpoints: 
Phase 1a Objectives and Endpoints: 
OBJECTIVES 
ENDPOINTS 
PRIMARY - SAFETY 
FPA150 Monotherapy 
• To evaluate the safety and tolerability of 
FPA150 as monotherapy in patients with 
advanced solid tumors treated at the Maximum 
Tolerated Dose (MTD) and/or Recommended 
Dose (RD) 
• To determine the MTD and/or RD of FPA150 
FPA150 Monotherapy 
• The incidence of Grade 3 and Grade 4 AEs and 
clinical laboratory abnormalities defined as DLTs 
• The incidence of AEs, clinical laboratory 
abnormalities, and ECG abnormalities 
FPA150 in Combination with Pembrolizumab 
• To evaluate the safety and tolerability of 
FPA150 in combination with pembrolizumab in 
patients with B7-H4+ ovarian cancer  
• To determine the MTD and/or RD of FPA150  
in combination with pembrolizumab in patients 
with B7-H4+ ovarian cancer 
FPA150 in Combination with Pembrolizumab 
• The incidence of AEs, clinical laboratory 
abnormalities, and ECG abnormalities 
• The incidence of Grade 3 and Grade 4 AEs and 
clinical laboratory abnormalities defined as DLTs 
SECONDARY - PHARMACOKINETIC 
FPA150 Monotherapy 
• To characterize the PK profile of FPA150 as 
monotherapy in patients with advanced solid 
tumors treated at the MTD and/or RD 
FPA150 Monotherapy 
• Area under serum concentration time curve (AUC) 
• Maximum serum concentration (Cmax) 
• trough serum concentration at the end of a dose 
interval (Ctrough) 
• Terminal Half-life (t1/2) 
• Volume of distribution at steady state (Vss) 
• Other parameters, such as dose proportionality, 
accumulation ratio, attainment of steady state, will 
also be calculated if the data are available 

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OBJECTIVES 
ENDPOINTS 
SECONDARY - IMMUNOGENICITY 
FPA150 Monotherapy 
• To characterize the immunogenicity of FPA150 
as monotherapy in patients with advanced solid 
tumors treated at the MTD and/or RD 
FPA150 Monotherapy 
• Immune response (ADAs) to FPA150 
EXPLORATORY - EFFICACY 
FPA150 Monotherapy 
• To evaluate the clinical benefit of FPA150 as 
monotherapy  
FPA150 Monotherapy 
• Objective response rate (ORR), defined as the total 
number of patients with confirmed responses of 
either complete response (CR) or partial response 
(PR) per Response Evaluation Criteria in Solid 
Tumors (RECIST v1.1) divided by the total number 
of patients who are evaluable for a response 
• Duration of response (DOR), defined as the time 
from onset of response (CR or PR) that is 
subsequently confirmed to the first observation of 
progressive disease or death due to any cause 
• Progression free-survival (PFS), defined as the time 
from the patient’s first dose to the first observation 
of progressive disease or death due to any cause 
FPA150 in Combination with Pembrolizumab 
• To evaluate the clinical benefit of FPA150 in 
combination with pembrolizumab in patients 
with B7-H4+ ovarian cancer 
FPA150 in Combination with Pembrolizumab 
• ORR, defined as the total number of patients with 
confirmed responses of either CR or PR per 
RECIST v1.1 divided by the total number of 
patients who are evaluable for a response 
• DOR, defined as the time from onset of response 
(CR or PR) that is subsequently confirmed to the 
first observation of progressive disease or death due 
to any cause  
• PFS, defined as the time from a patient’s first dose 
to the first observation of progressive disease or 
death due to any cause. 
EXPLORATORY - PHARMACOKINETICS 
FPA150 in Combination with Pembrolizumab 
• To characterize the pharmacokinetic (PK) 
profile of FPA150 in combination with 
pembrolizumab in patients with B7-H4+ ovarian 
cancer 
FPA150 in Combination with Pembrolizumab 
The following PK parameters will be derived from 
concentration-time data for FPA150 in combination 
with pembrolizumab when appropriate and applicable: 
• AUC 
• Cmax 
• Ctrough 
• Clearance (CL) 
• t1/2 
• Vss 
• Other parameters, such as dose proportionality, 
accumulation ratio, attainment of steady state, will 
also be calculated if the data are available for 
FPA150 Cmax and Ctrough as well as accumulation 

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OBJECTIVES 
ENDPOINTS 
ratio of Cmax and Ctrough for pembrolizumab may be 
calculated if the data are available 
EXPLORATORY - IMMUNOGENICITY 
FPA150 in Combination with Pembrolizumab 
• To characterize the immunogenicity of FPA150 
in combination with pembrolizumab in patients 
with B7-H4+ ovarian cancer 
FPA150 in Combination with Pembrolizumab 
• Immune response (ADAs) to FPA150 
• Immune response (ADAs) to pembrolizumab 
EXPLORATORY – PHARMACODYNAMIC BIOMARKERS 
FPA150 Monotherapy  
• To characterize the pharmacodynamic profile of 
FPA150 through an analysis of the immune cell 
infiltrate in pre-treatment and on-treatment 
tumor biopsies  
• To characterize the pharmacodynamic profile of 
FPA150 through evaluation of exploratory 
biomarkers in peripheral blood samples  
FPA150 Monotherapy  
• Changes in markers of tumor immune infiltrate 
• 
• Changes in selected pharmacodynamic biomarkers 
in peripheral blood samples 
FPA150 in Combination with Pembrolizumab 
• To characterize the pharmacodynamic profile of 
FPA150 in combination with pembrolizumab 
through an analysis of the immune cell infiltrate 
in pre-treatment and on-treatment tumor biopsies 
• To characterize the pharmacodynamic profile of 
FPA150 in combination with pembrolizumab 
through evaluation of exploratory biomarkers in 
peripheral blood samples  
FPA150 in Combination with Pembrolizumab 
• Changes in markers of tumor immune infiltrate 
• 
• Changes in selected additional pharmacodynamic 
markers in peripheral blood in patients treated with 
FPA150 in combination with pembrolizumab 
Phase 1b Objectives and Endpoints: 
OBJECTIVES 
ENDPOINTS 
PRIMARY - SAFETY 
FPA150 Monotherapy 
• To evaluate the safety and tolerability of 
FPA150 as monotherapy in patients with B7-
H4+ advanced solid tumors treated at the MTD 
and/or RD 
FPA150 Monotherapy 
• The incidence of AEs, clinical laboratory 
abnormalities, and ECG abnormalities 
FPA150 in Combination with Pembrolizumab 
• To evaluate the safety and tolerability of 
FPA150 in combination with pembrolizumab in 
patients with B7-H4+ ovarian cancer treated at 
the MTD and/or RD 
FPA150 in Combination with Pembrolizumab 
• The incidence of AEs, clinical laboratory 
abnormalities, and ECG abnormalities  in patients 
treated with FPA150 in combination with 
pembrolizumab 

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OBJECTIVES 
ENDPOINTS 
SECONDARY - EFFICACY 
FPA150 Monotherapy  
• To evaluate the clinical benefit of FPA150 as 
monotherapy in patients with B7-H4+ advanced 
solid tumors treated at the MTD and/or RD 
FPA150 Monotherapy  
• ORR, defined as the total number of patients with 
confirmed responses of either CR or PR per 
RECIST v1.1 divided by the total number of 
patients who are evaluable for a response 
• DOR, defined as the time from onset of response 
(CR or PR) that is subsequently confirmed to the 
first observation of progressive disease or death due 
to any cause  
• PFS, defined as the time from the patient’s first dose 
to the first observation of progressive disease or 
death due to any cause 
FPA150 in Combination with Pembrolizumab 
• To evaluate the clinical benefit of FPA150 in 
combination with pembrolizumab in patients 
with B7-H4 + ovarian cancer treated at the MTD 
and/or RD 
FPA150 in Combination with Pembrolizumab 
• ORR, defined as the total number of patients with 
confirmed responses of either CR or PR per 
(RECIST) v1.1 divided by the total number of 
patients who are evaluable for a response to FPA 
150 combined with pembrolizumab 
• DOR, defined as the time from onset of response 
(CR or PR) that is subsequently confirmed to the 
first observation of progressive disease or death due 
to any cause to FPA150 combined with 
pembrolizumab 
• PFS, defined as the time from the patient’s first dose 
to the first observation of progressive disease or 
death due to any cause  
SECONDARY - PHARMACOKINETICS 
FPA150 Monotherapy 
• To characterize the PK profile of FPA150 as 
monotherapy in patients with B7-H4+ advanced 
solid tumors treated at the MTD and/or RD 
FPA150 Monotherapy 
• AUC 
• Cmax 
• Ctrough 
• CL 
• t1/2 
• Vss  
• Other parameters, such as accumulation ratio, 
attainment of steady state, will also be calculated if 
the data are available 
SECONDARY - IMMUNOGENICITY 
FPA150 Monotherapy 
• To characterize the immunogenicity of FPA150 
as monotherapy in patients with B7-H4+ 
advanced solid tumors treated at the MTD 
and/or RD 
FPA150 Monotherapy 
• Immune response (ADAs) to FPA150 

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OBJECTIVES 
ENDPOINTS 
EXPLORATORY - PHARMACOKINETICS 
FPA150 in Combination with Pembrolizumab 
• To characterize the PK profile of FPA150 in 
combination with pembrolizumab in patients 
with B7-H4+ ovarian cancer treated at the MTD 
and/or RD  
• To characterize the PK profile of pembrolizimab 
in combination with FPA150 in patients with 
B7-H4+ ovarian cancer 
FPA150 in Combination with Pembrolizumab 
• The following PK parameters will be derived from 
concentration-time data for FPA150 in combination 
with pembrolizumab when appropriate and 
applicable: 
• AUC 
• Cmax 
• Ctrough 
• CL 
• t1/2 
• Vss 
• Other parameters, such as accumulation ratio, 
attainment of steady state, will also be calculated if 
the data are available for patients treated with 
FPA150 combined with pembrolizumab 
• Cmax and Ctrough as well as the accumulation ratio of 
Cmax and Ctrough for pembrolizumab may be 
calculated if the data are available 
EXPLORATORY - IMMUNOGENICITY 
FPA150 in Combination with Pembrolizumab 
• To characterize the immunogenicity of FPA150 
in combination with pembrolizumab in patients 
with B7-H4+ ovarian cancer treated at the MTD 
and/or RD 
• To characterize the immunogenicity of 
pembrolizumab in combination with FPA150 
patients with with B7-H4+ ovarian cancer 
treated at the MTD and/or RD 
FPA150 in Combination with Pembrolizumab 
• Immune response (ADAs) to FPA150 
• Immune response (ADAs) to pembrolizumab 
EXPLORATORY – PHARMACODYNAMIC BIOMARKERS 
FPA150 Monotherapy 
• To characterize the pharmacodynamic profile of 
FPA150 through an analysis of the immune cell 
infiltrate in pre-treatment and on-treatment 
tumor biopsies  
• To characterize the pharmacodynamic profile of 
FPA150 through evaluation of exploratory 
biomarkers in peripheral blood samples  
FPA150 Monotherapy 
• Changes in markers of tumor immune infiltrate 
• 
• Changes in selected pharmacodynamic biomarkers 
in peripheral blood samples 
FPA150 in Combination with Pembrolizumab 
• To characterize the pharmacodynamic profile of 
FPA150 in combination with pembrolizumab 
through an analysis of the immune cell infiltrate 
in pre-treatment and on-treatment tumor biopsies 
• To characterize the pharmacodynamic profile of 
FPA150 in combination with pembroliumab 
FPA150 in Combination with Pembrolizumab 
• Changes in markers of tumor immune infiltrate, 
• 

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OBJECTIVES 
ENDPOINTS 
through evaluation of exploratory biomarkers in 
peripheral blood samples  
• Changes in selected additional pharmacodynamic 
biomarkers in peripheral blood samples for patients 
treated with FPA150 in combination with 
pembrolizumab 
EXPLORATORY - EFFICACY 
FPA150 Monotherapy 
• To evaluate the clinical benefit of FPA150 as 
monotherapy in patients with B7-H4+ advanced 
solid tumors treated at the MTD and/or RD  
FPA150 Monotherapy 
• OS, defined as time from patient’s first dose to 
death due to any cause 
FPA150 in Combination with Pembrolizumab 
• To evaluate the clinical benefit of FPA150 in 
combination with pembrolizumab in patients 
with B7-H4+ ovarian cancer treated at the MTD 
and/or RD 
FPA150 in Combination with Pembrolizumab 
• OS, defined as time from patient’s first dose to 
death due to any cause 
 
Investigational Product:   
FPA150 drug product is supplied for IV administration as a sterile, aqueous, colorless to 
slightly yellowish, pyrogen-free solution supplied in single-use glass vials (5 mL). The 
composition of the drug product contains 20 mg/mL active ingredient, 20 mM sodium acetate, 
270 mM sucrose, 0.05% (w/v) polysorbate 20 at pH 5.0.   
A 20 mL preparation will be available for use in the second half of 2019.  The 20 mL vial is 
also supplied for IV administration as a sterile, aqueous, colorless to slightly yellowish, 
pyrogen-free solution supplied in single-use glass vials. The composition of the drug product 
contains 20 mg/mL active ingredient, 20 mM sodium acetate, 270 mM sucrose, 0.05% (w/v) 
polysorbate 20 at pH 5.0.    
Pembrolizumab is available for injection as a 50 mg lyophilized powder in single-use vial for 
reconstition and in 100 mg/4 mL (25 mg/mL) solution in single use vial.   
The lyophilized powder is reconstituted by adding 2.3 mL of Sterile Water for Injection, USP 
by injecting the water along the walls of the vial and not directly on the lyophilized powder 
(resulting concentration 25 mg/mL).  Slowly swirl the vial and allow up to 5 minutes for the 
bubbles to cear.  Do not shake the vial.  
The injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly 
yellow solution that requires dilution for intravenous infusion.  Each 1 mL of solution 
contains 25 mg of pembrolizumab and is formulated in: L-histidine (1.55 mg), polysorbate 80 
(0.2 mg), sucrose (70 mg) and water for Injection.  Refer to the pembrolizumab package insert 
for additional information. 

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Study Design:  
This is a Phase 1a/1b open-label, multicenter, study to evaluate the dosing, safety, tolerability, 
pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of FPA150 as 
monotherapy and in combination with pembrolizumab in patients with advanced solid tumors.  
This study includes a Phase 1a FPA150  Monotherapy Dose Escalation, Phase 1a FPA150 
Monotherapy Dose Exploration,a Phase 1a Combination Safety Lead-in (FPA150 in 
combination with pembrolizumab),  a Phase 1b FPA150 Monotherapy Dose Expansion, and a 
Phase 1b FPA150 Combination Dose Expansion (FPA150 in combination with 
pembrolizumab).  
Pre-screening of archival tumor tissue (or fresh biopsy if archival tissue is not available) is 
required to test for B7-H4 (transmembrane protein of the B7 family also known as B7S1, B7x, 
or VTCN1) expression levels by immunohistochemistry (IHC) at a central laboratory for all 
patients in the Phase 1a Monotherapy Dose Exploration, Phase 1a Combination Safety Lead-
in, Phase 1b Dose Expansion, and Phase 1b Combination Dose Expansion.  
Phase 1a Monotherapy and Combination Safety Lead-in and Phase 1b Combination Dose 
Expansion, will be conducted in the US only.  Phase 1b Monotherapy Dose Expansion will be 
conducted globally. 
Requirements for Archival Tumor Tissue, Fresh Biopsies: 
Required for all patients in Phase 1a FPA150 Monotherapy Dose Escalation: 
• Provision of archival tumor tissue (or fresh biopsy if archival tissue is not available) for 
retrospective biomarker analysis for all patients. 
Required for all patients in Phase 1a Combination Safety Lead-in: 
• Archival tumor tissue (or fresh biopsy required if archival tissue is not available) for pre-
screening to evaluate for B7-H4 expression levels through IHC testing performed at a 
central laboratory and for retrospective biomarker analysis at screening.  
Required for all patients in Phase 1a Monotherapy Dose Exploration: 
• Archival tumor tissue (or fresh biopsy required if archival tissue is not available) for 
prescreening to evaluate for B7-H4 expression levels through IHC testing performed at a 
central laboratory and for retrospective biomarker analysis at screening.  
• Fresh biopsies mandatory during screening and on-treatment (prior to C3D1) for expanded 
pharmacodynamic analysis. (please refer to Appendix 2 for additional information). 

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Required for all patients in Phase 1b Dose Expansion: 
• Archival tumor tissue (or fresh biopsy required if archival tissue is not available) for 
prescreening to evaluate for B7-H4 expresion levels through IHC testing and retrospective 
biomarker analysis at screening will be performed at a central laboratory.  Archival tissue 
for patients enrolled in Cohort 1b1 (Breast Cancer) must be within 24 months prior to pre-
screening. 
• Fresh biopsies mandatory for a subset of patients (at least 15 patients per 30-patient 
cohort) during screening and on-treatment (prior to C3D1), for expanded 
pharmacodynamic analysis. 
Study Design (Continued): Additional details are provided below for each study phase under 
Phase 1a Monotherapy Dose Escalation, Phase 1a Monotherapy Dose Exploration, Phase 1b 
Monotherapy Dose Expansion, Phase 1a Combination Safety Lead-In, and Phase 1b 
Combination Dose Expansion sections of this Synopsis. All study assessments are outlined in 
Appendix 1: Schedule of Assessments – Phase 1a and Phase 1b (monotherapy and 
combination).  
Phase 1a Monotherapy Dose Escalation:  
In Phase 1a Dose Escalation, cohorts are planned at doses from 0.01 to 20 mg/kg, and 
enrollment will depend on safety and tolerability. Phase 1a Dose Escalation will include an 
initial accelerated titration design followed by a standard 3+3 dose escalation design at dose 
levels ≥ 1 mg/kg until the maximum tolerated dose (MTD) and/or recommended dose (RD) 
for Phase 1b is determined. The proposed FPA150 dose levels for escalation are as follows: 
0.01 mg/kg once every 3 weeks (Q3W) 
• 0.03 mg/kg Q3W 
• 0.1 mg/kg Q3W 
• 0.3 mg/kg Q3W 
• 1 mg/kg Q3W 
• 3 mg/kg Q3W 
• 10 mg/kg Q3W 
• 20 mg/kg Q3W 
Review of safety, PK and pharmacodynamic profiles may inform decisions to add cohorts 
with alternative dose levels or dose regimens (eg, different dosing frequency, higher dose 
levels) in order to reach an optimal target exposure. 

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All dose escalation decisions will be based on the assessment of dose-limiting toxicities 
(DLTs) and overall safety and tolerability. Dose escalation decisions will be made after the 
last patient enrolled in each cohort has completed the first treatment cycle (ie, 21 days). Dose 
escalation decisions will be agreed upon by the Cohort Review Committee (CRC), consisting 
of at least the Sponsor’s Medical Monitor and defined quorum of Study Investigators. 
Dose-Limiting Toxicity Definitions: 
DLTs during Phase 1a Dose Escalation are defined as any of the following events regardless 
of attribution (except for those events clearly due to the underlying disease or extraneous 
causes): 
• Any Grade 3 or higher non-hematologic toxicity (except Grade 3 nausea, vomiting and 
diarrhea) occurring within the 21 days of treatment 
• Grade 3 nausea, vomiting, diarrhea lasting > 72 hours, despite optimal supportive care, 
occurring within first 21 days of treatment  
• Febrile neutropenia and/or documented infection with absolute neutrophil count (ANC) 
< 1.0 × 109 per L, Grade 4 neutropenia lasting for more than 7 days, Grade 4 
thrombocytopenia (< 25.0 × 109 per L), or Grade 3 thrombocytopenia (< 50.0–25.0 
× 109 per L) accompanied by bleeding within first 21 days of treatment 
• Aspartate aminotransferase/ alanine transaminase (AST/ALT) > 3 × upper limit of normal 
(ULN) and concurrent total bilirubin > 2 × ULN not related to liver involvement with 
cancer 
• Any Grade 4 laboratory value regardless of clinical sequelae 
• Other Grade 3 laboratory values that are not of clinical significance according to 
Investigator and Sponsor agreement that do not resolve within 72 hours 
The DLT evaluation interval begins on the first day of treatment upon start of infusion and 
continues for 21 days. In Phase 1a Monotherapy Dose Escalation, patients’ second dose must 
be at least 21 days after the first dose. Patients who receive at least one dose of study drug 
during the 21-day evaluation interval, or patients who discontinue study treatment for drug-
related AEs before the DLT evaluation interval is complete, will be considered evaluable for 
DLT determination. In consultation with Investigators, the Sponsor may open cohorts at dose 
levels between the dose levels proposed in the protocol. 
An accelerated titration design enrolling at least 1 patient at each dose level is planned for 
dose levels 0.01, 0.03, 0.1 and 0.3 mg/kg. Dose escalation to the next dose level may proceed 
after at least 1 patient completes the 21-day evaluation interval. If a single patient experiences 
a DLT or at least 2 patients experience moderate AEs (at any dose level) during the 21-day 
evaluation interval, additional patients will be enrolled at the current dose level and standard 
3+3 dose escalation criteria will apply for that cohort as well as all subsequent dosing cohorts. 

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Moderate AEs are defined as ≥ Grade 2 AEs regardless of attribution (except for those events 
clearly due to the underlying disease or extraneous causes). Grade 2 laboratory values will not 
be considered as moderate AEs for this purpose unless accompanied by clinical sequelae.  
The algorithm outlined in the table below will be used for all standard 3+3 dose escalation 
decisions in Phase 1a Monotherapy Dose Escalation. If not already applied at a lower dose 
level according to the criteria stated above, enrollment at all dose levels ≥ 1 mg/kg will follow 
a standard 3+3 dose escalation design. 
Algorithm for 3+3 Dose Escalation Decisions in Phase 1a Monotherapy Dose Escalation: 
Number of Patients with 
DLT at a Given Dose Level 
Dose Escalation Decision Rule 
0/3 
Enroll 3 patients at next dose level (next/higher cohort) 
1/3 
Enroll 3 additional patients at current dose level (current cohort) 
≥ 2/3 
Stop enrollment. Enter 3 more patients at the previous dose level 
(previous/lower cohort), if only 3 were previously entered, or at an 
intermediate dose level 
1/6 
Enroll 3 patients at next dose level (next/higher cohort) 
≥ 2/6 
Stop enrollment. Enter 3 more patients at the lower dose level (previous/lower 
cohort), if only 3 were previously entered, or at an intermediate dose level 
Abbreviations: DLT = dose-limiting toxicity. 
The MTD and/or RD of FPA150 for Phase 1a monotherapy will be identified based on an 
evaluation of the overall safety, tolerability, PK, pharmacodynamics, and preliminary 
efficacy. The RD will take into account toxicities observed both during and beyond the DLT 
evaluation period as well as dose reductions and discontinuations due to toxicity that do not 
meet the DLT criteria. The RD, therefore, may or may not be the same as the identified MTD. 
For example, if the MTD is not reached, or if data from subsequent cycles of treatment from 
Phase 1a provide additional insight on the safety profile, then the RD may be a different, 
though not higher, dose than the MTD.  
The MTD will be at a dose level where ≤ 1/3-6 patients reported a DLT. The RD will be a 
dose where ≤ 1/3-6 patients reported a DLT, but may be lower than the MTD.  
In the event that no MTD is identified and drug exposure exceeds what is deemed necessary 
based on nonclinical pharmacology data or the clinical PK and pharmacodynamic data 
(if available), the Sponsor and the Investigators may make a decision to discontinue dose 
escalation. 

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Phase 1a Monotherapy Dose Exploration:  
Phase 1a FPA150 monotherapy Dose Exploration may include cohorts that may enroll beyond 
3 patients whose tumors express high levels of B7-H4 protein and/or have varying levels of 
B7-H4 expression 
 
 to further evaluate safety, PK, 
pharmacodynamics, and clinical activity at that dose (to be conditional upon the dose level 
clearing DLT criteria). Toxicities observed in these patients will contribute to the overall 
assessment of safety and tolerability, but will not be included in the formal DLT calculations 
per Protocol Table 5. 
The proposed cohorts are: 
Proposed Dose Cohort/Level for Phase 1a Monotheraphy Dose Exploration 
Cohort 
Dose 
Regimen 
B7-H4 Status 
1aE1 
FPA150 3 mg/kg  
Q3W 
High 
1aE2 
FPA150 10 mg/kg 
Q3W 
High 
1aE3 
FPA150 monotherapy MTD/RD 
Q3W 
 
Abbreviations: MTD = maximum tolerated dose; Q3W = once every 3 weeks; RD = recommended dose. 
 
Phase 1a Combination Safety Lead-in (Ovarian B7-H4+ Patients Only):  
Once the MTD and/or RD of FPA150 monotherapy is identified, the Sponsor will open a 
Safety Lead-in for the combination of FPA150 and pembrolizumab.  At least 3 patients will 
be enrolled at the MTD and/or RD of FPA150 monotherapy combined with 200 mg 
pembrolizumab Q3W and evaluated for DLTs by the CRC. Once the RD for the combination 
is identified, the Sponsor may treat additional patients for a total of up to 10 patients treated at 
the RD of FPA150 + pembrolizumab. If required, the dose of FPA150 may be reduced in 
accordance with the algorithm for de-escalation described below. The proposed dose levels 
are: 
Proposed Dose Cohort/Levels for Phase 1a Combination Safety Lead-in (FPA150 in 
Combination with Pembrolizumab) 
Cohort 
Dose 
Regimen 
1aC1 
FPA150 (RD) + pembrolizumab 200 mg IV infusion 
Q3W 
1aC2 
FPA150 (dose level -1) + pembrolizumab 200 mg IV infusion 
Q3W 
1aC3 
FPA150 (dose level -2) + pembrolizumab 200 mg IV infusion 
Q3W 
Abbreviations: IV = intravenous; Q3W = once every 3 weeks; RD = recommended dose. 
 

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The de-escalation scheme will follow the same dose levels used in Phase 1a dose escalation. 
The Sponsor may evaluate lower or intermediate dose levels of FPA150 based on emerging 
safety data and in consultation CRC . The DLT criteria for the combination of FPA150 and 
pembrolizumab will be the same as those for FPA150 monotherapy, with the following 
additional considerations:  
Additional DLT Considerations for FPA150 in combination with Pembrolizumab  
Because pembrolizumab is a known immune checkpoint inhibitor and one of the proposed 
mechanisms of action of FPA150 is immune checkpoint blockade, immune-related adverse 
events (irAEs) are anticipated with this combination. An irAE is defined as a clinically 
significant AE that is associated with study drug exposure, of unknown etiology, and is 
consistent with an immune-mediated mechanism. Based on that background, the first 
occurrence of the following irAEs will not be considered a DLT because they are expected 
with immune therapy:  
• Grade 3 tumor flare (defined as local pain, irritation, or rash localized at sites of known or 
suspected tumor) 
• Grade 3 rash 
• Grade 3 immune-related adverse event (irAE) that resolved to a Grade 1 or less within 
14 days 
• Transient (resolving within 6 hours of onset) Grade 3 infusion-related AE 
A second occurrence of these events (except Grade 3 tumor flare) either in the same or 
different patient during the DLT window will be considered a DLT 
The DLT evaluation interval begins on the first day of treatment upon start of infusion and 
continues for 21 days. The algorithm outlined in the table below will apply for dosing 
decisions. The dose of FPA150 may be lowered as needed in response to DLTs. The MTD 
and/or RD of FPA150 in combination with pembrolizumab will be a dose where 
≤ 1/3-6 patients encounter a DLT.  

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Algorithm for Dose De-Escalation Decisions for Phase 1a Combination Safety Lead-In  
Number of Patients with DLT 
at a Given Dose Level 
Dosing Decision Rule 
0/3 
Proceed with enrollment of up to 10 total patients at that dose level for 
additional safety assessment 
1/3 
Enroll 3 additional patients at current dose level (current cohort) 
≥ 2/3 
Stop enrollment at current cohort and de-escalate FPA150 to one dose level 
below current dose  
1/6 
Proceed with enrollment of up to 10 total patients at that dose level 
≥ 2/6 
Stop enrollment at current cohort and de-escalate FPA150 to one dose level 
below current dose.  
 
Phase 1b FPA150 Monotherapy and Phase 1b Combination Dose Expansion:  
Enrollment in Phase 1b will begin when the MTD and/or RD has been identified by the CRC. 
The MTD and/or RD determination will be based on overall safety, tolerability, objective 
response, PK, and pharmacodynamics from the Phase 1a Monotherapy Dose Escalation and 
Phase 1a Combination Safety Lead-In portions of the study and estimates of efficacious 
exposures extrapolated from nonclinical data.  
Phase 1b will initially consist of cohorts of up to 30 patients each in the following 3 tumor 
types with B7-H4 expression levels determined by IHC.  There will be three FPA150 
monotherapy cohorts and one FPA150 combination cohort at the MTD and/or RD: 
Phase 1b Expansion Cohorts, Tumor Types, and Therapy 
Cohort 
Tumor Type 
Therapy Type (Monotherapy or Combination) 
1b1 
Breast cancer 
Monotherapy: FPA150 
1b2 
Ovarian cancer 
Monotherapy: FPA150 
1b3 
Endometrial cancer 
Monotherapy: FPA150 
1bC1 
 Ovarian cancer 
Combination: FPA150 with pembrolizumab 
 
Based on emerging clinical and translational data from the study, cohorts for additional tumor 
types with FPA150 as monotherapy or in combination may be opened during the trial (not to 
exceed 30 patients in any individual cohort and not exceed 7 cohorts). 
Dosing: FPA150 will be administered as a single agent in a 60-minute (± 5 minutes) IV 
infusion Q3W, on Day 1 of each 21-day cycle. The dose of FPA150 will be based on body 
weight at Cycle 1 Day 1 (C1D1). After Cycle 1, the FPA150 dose will be recalculated at each 
infusion visit only if the patient’s weight has changed > 10% from Cycle 1, Day 1.  There is 
no pre-specified maximum number of doses of FPA150 for patients receiving monotherapy. 

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Patients may continue receiving FPA150 monotherapy according to their study specified 
cohort/dose until Investigator-assessed clinical progressive disease, unacceptable toxicity, or 
the patient meets any of the other protocol-specified withdrawal criteria (refer to Section 7). 
For combination cohorts, pembrolizumab will be administered at a dose of 200 mg IV over 
30 minutes (± 5 minutes) starting on C1D1 after the completion of  FPA150 infusion. Dosing 
for combination cohorts will be repeated on Day 1 of each 21-day cycle. Patients in the 
combination cohort may receive one or both drugs in combination according to their study 
specified cohort/dose until Investigator-assessed clinical progressive disease, unacceptable 
toxicity, or the patient meets any of the other protocol-specified withdrawal criteria (refer to 
Section 7).  Patients treated with the combination would be able to receive pembrolizumab 
treatment for up to 24 months.  If one of the two drugs has to be discontinued, patients may 
continue to receive the other drug alone.  
Treatment beyond disease progression may be allowed in patients with progressive disease 
according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) if the 
benefit/risk assessment favors continued administration of study treatment (eg, if patients are 
continuing to experience clinical benefit as assessed by the Investigator, and tolerating 
treatment). 
Study Duration: The duration of study for an individual patient includes screening (up to 
28 days), treatment and an End of Treatment (EOT) follow-up period which will include visits 
at approximately 28 (±7) days and 100 (±7) days after the last dose. Since all patients are 
eligible to be treated until disease progression, the actual treatment duration for each 
individual patient will vary depending on the anticipated time to progression for their 
respective tumor type. Treatment beyond disease progression may be allowed in patients with 
initial RECIST v1.1 defined progressive disease if the benefit/risk assessment favors 
continued administration of study treatment (eg, patients are continuing to experience clinical 
benefit as assessed by the Investigator, and tolerating treatment). 
In addition, patients enrolled in either the Phase 1b Monotherapy Dose Expansion or Phase 1b 
Combination Dose Expansion will be followed for survival for up to 2 years. 
Number of Patients:  
The total number of patients planned for this study is estimated to be up to 278.   
Phase 1a will enroll up to 68 patients depending on incidence of DLTs; this includes 23 to 
26 patients enrolled in the Phase 1a Monotherapy dose escalation portion, 6 to 22 patients 
enrolled in the Phase 1a Combination Safety Lead-in portion, and up to 20 patients that may 
receive FPA150 in the Phase 1a Monotherapy Dose Exploration portion.  

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Phase 1b will enroll up to 210 patients.  Initially 3 tumor-type specific cohorts of up to 
30 patients each will be enrolled to receive FPA150 Monotherapy in Phase 1b.  One 
additional tumor-type specific cohort evaluating FPA150 in combination with pembrolizumab 
will be enrolled.  No individual Phase 1b Dose Expansion cohort will exceed 30 patients and 
the total number of Phase 1b cohorts will not exceed 7.  Up to 3 additional Phase 1b cohorts 
(up to 30 patients each) may be determined at a later time upon emerging data.  
Eligibility Criteria  
Inclusion Criteria: Phase 1a Inclusion Criteria (Monotherapy and Combination Safety 
Lead-in Therapy) 
Patients enrolling into Phase 1a must meet all of the following inclusion criteria: 
1) Histologically confirmed solid tumors except primary central nervous system (CNS) 
tumors. 
2) Disease that is unresectable, locally advanced, or metastatic. 
3) Able to understand and sign an Institutional Review Board / Independent Ethics 
Committee (IRB/IEC)  approved Informed Consent Form (ICF) prior to any study-
specific evaluation. 
4) Patients should be refractory to or intolerant of existing therapy(ies) known to provide 
clinical benefit for their condition.  
5) All patients must have at least one measurable lesion at baseline according to RECIST 
v1.1; tumor sites situated in a previously irradiated area, or in an area subjected to other 
loco-regional therapy, are not considered measurable unless there has been demonstrated 
progression in the lesion. 
6) Adequate washout for prior anti-cancer therapy (ie, ≥ 5 half-lives or 4 weeks since the 
last dose, whichever is shorter). 
7) Availability of archival tumor tissue and consent to providing archival tumor for 
retrospective biomarker analysis, or patient must undergo a fresh tumor biopsy during 
screening if archival tissue is not available (a biopsy is required for patients in the Phase 
1a Dose Exploration portion). 
8) Age ≥ 18 years at the time the ICF is signed. 
9) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 
10) Life expectancy of at least 3 months in the opinion of the Investigator. 
11) Willing and able to comply with all study procedures. 
12) Prior radiotherapy must be completed at least 2 weeks before the first dose of study drug. 

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13) Prior radiopharmaceuticals (eg, strontium, samarium) must be completed at least 8 weeks 
before the first dose of study drug.  
14) Prior surgery that requires general anesthesia must be completed at least 1 week before 
first dose of study drug administration. Surgery requiring local/ epidural anesthesia must 
be completed at least 72 hours before first dose of study drug administration. Patients 
must have recovered from any surgery. 
15) Screening laboratory values must meet the following criteria: 
Hematologic: 
a. 
Neutrophils ≥ 1200 cells/ µL 
b. 
Platelets ≥ 75 × 103/ µL 
c. 
Hemoglobin (Hb) ≥ 9.0 g/dL 
Renal: 
d. 
Serum creatinine < 1.5 × ULN or creatinine clearance (CrCl) of ≥ 40 mL/ minute 
(using Cockcroft/Gault Formula) 
Female CrCl 
(140 – age in years) × (weight in kg) × 0.85 
72 × (serum creatinine in mg/dL) 
 
Male CrCl 
(140 – age in years) × (weight in kg) 
72 × (serum creatinine in mg/dL) 
 
Hepatic: 
e. 
AST and ALT ≤ 3× ULN (AST and ALT < 5× ULN in patients with liver metastases 
is permitted) 
f. 
Bilirubin < 1.5× ULN (except patients with Gilbert's syndrome, who must have total 
bilirubin < 3 mg/dL) 
16) Negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test ≤ 96 hours 
prior to treatment on Cycle 1, Day 1 (women of childbearing potential only). 
17) In sexually active patients (women of child bearing potential and males), willingness to 
use 2 effective methods of contraception, of which 1 must be a physical barrier method 
(eg condom, diaphragm, or cervical/vault cap) until 6 months after the last dose of 
FPA150. Other effective forms of contraception include: 
• Permanent sterilization (hysterectomy and/or bilateral oophorectomy, or bilateral 
tubal ligation with surgery, or vasectomy) at least 6 months prior to Screening 
• Women of childbearing potential who are on stable oral contraceptive therapy or 
intrauterine or implant device for at least 90 days prior to the study, or abstain from 
sexual intercourse as a way of living 

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50)  For Phase 1a Combination Safety Lead-in Patients ONLY:  
50.01) B7-H4 positive ovarian cancer 
50.02) Histologically or cytologically confirmed  diagnosis of recurrent epithelial 
ovarian, primary peritoneal, or fallopian tube carcinoma  that is refractory to 
existing therapy(ies) known to provide clinical benefit 
50.03)  Progressive disease on or after  at least two prior regimens of treatment 
including at least one platinum-containing regimen, or unable to tolerate 
additional chemotherapy 
50.04)  No prior therapy with an anti-PD1 or PD-L1-directed agent   
Phase 1b (Monotherapy and Combination) Inclusion criteria: 
Patients enrolling into Phase 1b must meet all of the following inclusion criteria: 
18) All Inclusion Criteria for Phase 1a (Exception: Inclusion Criterion #1). 
19) Positive for B7-H4 expression in an archival or fresh tumor sample as evaluated by an 
accompanying validated central laboratory IHC assay. 
20) History of other malignancy is permitted provided it has been definitively treated with no 
evidence of recurrence within the past 2 years (Exception: Definitively treated non-
melanoma skin cancer, lobular cancer in situ, and cervical cancer in situ within 2 years 
are permitted). 
Additional Cohort-Specific Inclusion Criteria For Phase 1b (Monotherapy and 
Combination) 
Cohort 1b1 Breast Cancer: 
Triple Negative Breast Cancer (TNBC) 
21.01) Histologically or cytologically confirmed metastatic TNBC  
21.02) At least two prior lines of systemic chemotherapy with at least one being administered 
in the metastatic setting 
HR+ Breast Cancer  
21.03) Histologically or cytologically confirmed metastatic HR+ breast carcinoma 
21.04) Patients must have received at least two prior lines of hormonal therapy 
21.05) Patients must have received at least one prior line of systemic chemotherapy (in the 
adjuvant or metastatic setting) 

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Cohort 1b2 Ovarian Cancer: 
22.01) Histologically or cytologically confirmed diagnosis of recurrent epithelial ovarian, 
primary peritoneal, or fallopian tube carcinoma that is refractory to existing 
therapy(ies) known to provide clinical benefit 
22.02) Progressive disease on or after at least two prior regimens of treatment including at 
least one platinum-containing regimen, or unable to tolerate additional chemotherapy 
Cohort 1b3 Endometrial Cancer: 
23.01) Histologically or cytologically confirmed recurrent or persistent endometrial 
carcinoma that is refractory to curative or established treatments 
23.02) Progressive disease on or after at least one prior regimen of systemic chemotherapy, or 
unable to tolerate systemic chemotherapy  
Cohort 1bC1 Ovarian Cancer: 
24.01)  Histologically or cytologically confirmed  diagnosis of recurrent epithelial ovarian, 
primary peritoneal, or fallopian tube carcinoma  that is refractory to existing 
therapy(ies) known to provide clinical benefit 
24.02)  Progressive disease on or after  at least two prior regimens of treatment including at 
least one platinum-containing regimen, or unable to tolerate additional chemotherapy 
24.03)  No prior therapy with an anti-PD1 or PD-L1-directed agent   
No waivers will be granted for any of these inclusion criteria. 
Eligibility Criteria  
Exclusion Criteria (Phase 1a And Phase 1b)  
Patients who meet ANY of the following criteria will be excluded from study entry: 
1) Immunosuppressive doses of systemic medications, such as steroids or absorbed topical 
steroids (doses > 10 mg/day prednisone or equivalent daily) must be discontinued at least 
2 weeks before the first dose of study drug. Short courses of high dose steroids, 
continuous low dose (prednisone < 10 mg/day), inhaled, intranasal, intraocular, and joint 
injections of steroids are allowed. 
2) Decreased cardiac function with New York Heart Association (NYHA) > Class 2 at 
screening. 
3) Uncontrolled or significant heart disorder such as unstable angina 

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4) QT interval corrected for heart rate (QTc) per institutional guidelines > 450 msec for 
males or > 470 msec for females at screening. 
5) History of anti-drug antibodies (ADAs), severe allergic, anaphylactic, or other infusion-
related reaction to a previous biologic agent.  
6) Known hypersensitivity to any component of  FPA150 investigational product (IP) 
formulation and/or pembrolizumab. 
7) Vaccines (eg, human papilloma virus [HPV] vaccine) within 4 weeks before the first dose 
of study drug. The inactivated seasonal influenza vaccine can be given to patients before 
treatment and while on therapy without restriction. Influenza vaccines containing live 
virus or other clinically indicated vaccinations for infectious diseases (ie, pneumovax, 
varicella, etc.) may be permitted, but must be discussed with the Sponsor’s Medical 
Monitor and may require a study drug washout period prior to and after administration of 
the vaccine. 
8) Current unresolved infection or history of chronic, active, clinically significant infection 
(viral, bacterial, fungal, or other) which, in the opinion of the Investigator, would 
preclude the patient from exposure to a biologic agent or may pose a risk to patient 
safety. 
9) Patients with abnormal serum chemistry values that in the opinion of the Investigator are 
considered to be clinically significant. This includes patients who show clinical signs and 
symptoms related to their abnormal serum chemistry values, as well as patients whose 
serum chemistry values are asymptomatic, but clinically significant according to the 
Investigator (eg, hypokalemia or hyponatremia). 
10) Any uncontrolled medical condition or psychiatric disorder which, in the opinion of the 
Investigator, would pose a risk to patient safety or interfere with study participation or 
interpretation of individual patient results. 
11) Pregnant or breastfeeding. 
12) Active, known, or suspected autoimmune disease. Patients with Type I diabetes mellitus, 
hypothyroidism requiring only hormone replacement, skin disorders (such as vitiligo, 
psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to 
recur in the absence of an external trigger, are permitted to enroll. 
13) Known history of testing positive for human immunodeficiency virus (HIV) 1 or 2 or 
known acquired immunodeficiency syndrome (AIDS). 
14) Positive test for hepatitis B virus surface antigen (HBsAg) or detectable hepatitis C virus 
ribonucleic acid (HCV RNA) indicating acute or chronic infection. 
15) Ongoing adverse effects from prior treatment > Grade 1 (with the exception of Grade 2 
alopecia or peripheral neuropathy) based on National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE). 

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16) Symptomatic interstitial lung disease or inflammatory pneumonitis. 
17) Untreated or active CNS or leptomeningeal metastases. Patients are eligible if metastases 
have been treated and patients are neurologically returned to baseline or neurologically 
stable (except for residual signs or symptoms related to the CNS treatment) for at least 
2 weeks before the first dose of study drug. 
18) Evidence of coagulopathy or bleeding diathesis. Patients receiving stable therapeutic 
doses of anti-coagulants will be permitted. 
19) Transfusion of blood or platelets completed within 72 hours before the first dose of study 
drug. 
20) Any uncontrolled inflammatory GI disease including Crohn’s Disease and ulcerative 
colitis 
21) For Cohort 1b1 only: Patients with HER2 positive disease 
No waivers will be granted for any of these exclusion criteria. 
Tests and Observations: Safety assessments include vital signs, body weight, physical exam, 
ECOG score, laboratory tests (hematology, serum chemistries, and urinalysis), 
electrocardiograms (ECGs), and monitoring of adverse events (AEs) and concomitant 
medications. 
Archival tumor tissue (or a fresh tumor biopsy required during screening) will be collected for 
biomarker analysis to explore the relationship between baseline target levels, tumor immune 
phenotype and pharmacodynamic response, and is mandatory for all patients.  
Pre- and on-treatment tumor tissue will be mandatory for all patients in Phase 1a 
Monotherapy Dose Exploration, Phase 1a Combination Safety Lead-in and a subset of 
patients (at least 15 patients per cohort of 30 patients) in Phase 1b Dose Expansion 
(monotherapy and in combination with pembrolizumab) for expanded pharmacodynamic 
analysis. 
Efficacy assessments will consist of radiographic imaging that is performed every 6 weeks. 
Responses will be assessed according to RECIST v1.1.  
Statistical Methods: 
Sample Size Determination: 
This study is designed as a dose escalation, dose exploration, and dose expansion study with 
objectives that include determination of an MTD and/or RD and assessments of the safety and 
tolerability of FPA150 alone and in combination with pembrolizumab. The sample size of this 
study was not determined by statistical considerations. The total number of patients planned 
for this study is estimated to be up to 278.  

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Phase 1a will enroll up to 68 patients. The 68 patients include 23 to 26 patients in the Phase 1a 
Monotherapy Dose Escalation cohorts, 6 to 22 patients in the Phase 1a Combination Safety 
Lead-in and up to 20 additional patients in the Phase 1a Dose Exploration (10 patients with 
B7-H4 high and 10 patients with low/no B7-H4 expression; refer to Section 4.1.3) to further 
evaluate safety, PK, pharmacodynamics, and clinical activity at one or more dose levels (to be 
conditional upon the dose level clearing DLT criteria).  
For the objective of estimating the overall response rate (ORR) of FPA150 in Phase 1b Dose 
Expansion, it is estimated that up to 30 patients will be enrolled to ensure 25 evaluable 
patients in each cohort. The following table displays the corresponding 2-sided 90% 
confidence interval (CI) and the precision for the various observed response rates based on 
25 evaluable patients.  The sample size of 25 is chosen to ensure that it will allow to exclude 
10% when the observed ORR is 24% or higher. 
Phase 1b will enroll up to 210 patients with specific tumor types. Up to 30 patients are 
planned for each of three FPA150 Monotherapy expansion cohorts and the one FPA150 in 
combination with pembrolizumab cohort.  Additional cohorts of up to 30 patients each may be 
enrolled (not to exceed 7 cohorts), based on emerging clinical and translational data. 
Two-Sided 90% Confidence Intervals of the Observed Response Rates  
Sample Size 
Observed Response Rate 
90% CI 
Precision (longest one-sided 
CI length*) 
25 
5/25 (20%) 
(8%, 38%) 
18% 
6/25 (24%) 
(11%, 42%) 
18% 
7/25 (28%) 
(14%, 46%) 
18% 
8/25 (32%) 
(17%, 50%) 
18% 
9/25 (36%) 
(20%, 54%) 
18% 
10/25 (40%) 
(24%, 58%) 
18% 
Abbreviations: CI = confidence interval. 
*Distance from the observed response rate to the lower or upper CI boundary. 
Safety Analysis: 
Safety analyses will be performed separately within both phases of the study and for all 
patients combined. Data from all patients that receive at least one dose of FPA150 
monotherapy or part of one dose of either pembrolizumab or FPA150 in the combination 
cohort will be included in the safety analyses. AEs, clinical laboratory information, vital signs, 
ECOG performance status, weight, ECGs, and concomitant medications/procedures will be 
tabulated and summarized. In addition, the incidence of DLTs in Phase 1a will be 
summarized. 

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Efficacy Analysis: 
The ORR will be summarized with frequencies and percentages with 90% confidence interval 
(CI). The duration of response (DOR) for complete response (CR) and partial response (PR) 
patients for all treated patients will be summarized with descriptive statistics (N, arithmetic 
mean, standard deviation (SD), median, minimum, and maximum). The ORR, DOR, and PFS 
will be determined using RECIST v1.1. Kaplan-Meier methodology will be used to estimate 
median DOR and PFS and corresponding 95% CI.  A 2-stage design will be used to determine 
the actual enrolled subjects. Sponsor will evaluate efficacy in phase 1b on an ongoing basis 
and may suspend or terminate enrollment in specific cohorts if <=1 response (CR or PR per 
RECIST 1.1) is observed in the first 16 patients enrolled in each cohort. . In this case, the 
probability of early termination is 0.81 with 0.05 responder rate for futility and 0.2 responder 
rate for efficacy. 
Pharmacokinetic Analysis: 
Individual and mean (±SD) serum FPA150 concentration-time data from monotherapy will be 
tabulated and plotted by dose level/cohort. PK parameters will be tabulated and summarized 
by dose level/cohort when appropriate and applicable. The impact of immunogenicity on 
FPA150 exposure will be assessed, tabulated, and summarized by dose level as data allow. 
For cohorts of FPA150 in combination with pembrolizumab samples for PK analysis will be 
collected and held. Individual and mean (±SD) serum concentration-time data for FPA150 and  
pembrolizumab may be tabulated and plotted by dose level/cohort.  PK parameters for the 
combination may be tabulated and summarized by dose level/cohort when appropriate and 
applicable.  
Immunogenicity Analysis: 
A baseline ADA-positive subject is defined as a subject who has an ADA positive sample at 
baseline. An ADA-positive subject is a subject with at least one ADA-positive sample relative 
to baseline after initiation of the treatment. The frequency distribution of baseline 
ADA-positive subjects and ADA-positive subjects after initiation of the treatment will be 
summarized for FPA150 and FPA150 in combination with pembrolizumab, respectively. 
Pharmacodynamic Analysis: 
A list of potential pharmacodynamic analyses is provided in Appendix 3. Selected 
pharmacodynamic biomarkers will be assessed for meaningful changes between pretreatment 
and on-treatment tumor and peripheral blood samples. 

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Schedule of Assessments:  
The Schedule of Assessments – Phase 1a and Phase 1b is provided in Appendix 1. 
The Schedule of Pharmacokinetic, Immunogenicity, and Pharmacodynamic Blood Sample 
Collection is provided in Appendix 2.  
The List of Pharmacodynamic Analyses is provided in Appendix 3. 
 
 

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TABLE OF CONTENTS 
Protocol Approval Signature Page .......................................................................................... 2 
Declaration of the Investigator ................................................................................................ 3 
Document History ..................................................................................................................... 4 
1 
Protocol Synopsis ............................................................................................................... 5 
Table of Contents .................................................................................................................... 28 
List of Tables ........................................................................................................................... 32 
List of Figures .......................................................................................................................... 33 
List of Abbreviations and Definitions ................................................................................... 34 
2 
Introduction ...................................................................................................................... 38 
 
Study Rationale ................................................................................................. 39 
 
Background ........................................................................................................ 40 
 
50, an Anti-B7-H4 Antibody ................................................................ 40 
 
Nonclinical Pharmacology Studies with FPA150 ................................. 40 
2.2.2.1 
In Vitro Biology ................................................................... 40 
2.2.2.2 
In Vivo Pharmacology ......................................................... 41 
 
Nonclinical Pharmacokinetics .............................................................. 43 
 
Toxicology ............................................................................................ 44 
 
Clinical Experience with FPA150 ........................................................ 45 
2.2.5.1 
Study Population: ................................................................. 45 
2.2.5.2 
Patient Characteristics .......................................................... 45 
2.2.5.3 
Study Drug Exposure ........................................................... 45 
2.2.5.4 
Dose Limiting Toxicities: .................................................... 46 
2.2.5.5 
Adverse Events: ................................................................... 46 
2.2.5.6 
Serious Adverse Events........................................................ 46 
2.2.5.7 
Deaths ................................................................................... 46 
 
Pembrolizumab Background ................................................................. 46 
 
Rationale for Combination with Pembrolizumab ................................. 47 
 
Benefit/ Risk Assessment .................................................................................. 47 
3 
Objectives and Endpoints ............................................................................................... 49 
 
Phase 1a Objectives and Endpoints ................................................................. 49 
 
Phase 1b Objectives and Endpoints ................................................................. 51 
4 
Study Design ..................................................................................................................... 55 
 
Overall Design ................................................................................................... 55 
 
Cohort Review Committee ................................................................... 58 
 
Study Design: Phase 1a Dose Escalation .............................................. 58 
4.1.2.1 
Phase 1a Combination Safety Lead-in (Ovarian B7-H4+ 
Patients Only) ....................................................................... 58 

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4.1.2.2 
Definition of a Dose-Limiting Toxicity ............................... 59 
4.1.2.3 
Dose-Limiting Toxicity Evaluation and Dose Escalation 
(FPA150 Monotherapy and Combination Safety Lead-in) .. 60 
4.1.2.4 
Determination of the Recommended Dose or Maximum 
Tolerated Dose ..................................................................... 62 
 
Study Design: Phase 1a Dose Exploration ............................................ 62 
 
Study Design: Phase 1b Dose Expansion ............................................. 63 
 
Number of Patients ............................................................................................ 64 
 
Patient and Study Completion ......................................................................... 64 
 
End of Study Definition .................................................................................... 64 
 
Scientific Rationale for Study Design .............................................................. 65 
 
Justification for Dose and Dosing Regimen .................................................... 65 
 
Patient Selection ................................................................................................ 66 
5 
Study Population .............................................................................................................. 67 
 
Inclusion Criteria .............................................................................................. 67 
 
Phase 1a Inclusion Criteria (Monotherapy and Combination 
Therapy) ................................................................................................ 67 
 
Phase 1b Inclusion Criteria (Monotherapy and Combination 
Therapy) ................................................................................................ 69 
 
Additional Cohort-Specific Inclusion Criteria for Phase 1b 
(Monotherapy and Combination Therapy) ........................................... 69 
 
Eligibility Criteria ............................................................................................. 70 
 
Lifestyle Restrictions ......................................................................................... 72 
 
Screen Failures .................................................................................................. 72 
6 
Treatments ........................................................................................................................ 73 
 
Treatments Administered ................................................................................. 73 
 
FPA150 Identity .................................................................................... 73 
 
Pembrolizumab ..................................................................................... 73 
 
Treatment Packaging, Labeling, and Storage ................................................ 74 
 
FPA150 ................................................................................................. 74 
 
Pembrolizumab ..................................................................................... 74 
 
Administration and Preparation ...................................................................... 74 
 
FPA150 ................................................................................................. 74 
 
Pembrolizumab ..................................................................................... 75 
 
Dose Modifications ............................................................................................ 76 
 
Dose Modification Based on Weight .................................................... 76 
 
Dose Escalation within a Cohort........................................................... 76 
 
Toxicity at Lowest Dose Level ............................................................. 77 

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Dose Modification Criteria for FPA150 ............................................... 77 
 
Dose Modification Criteria (Pembrolizumab) including Immune 
Related AEs .......................................................................................... 78 
 
Dose Interruptions During Study Treatment Administration ............... 78 
 
Maximum Duration of Treatment ................................................................... 79 
 
Method of Treatment Assignment ................................................................... 79 
 
Blinding .............................................................................................................. 79 
 
Study Drug Accountability ............................................................................... 79 
 
Treatment Compliance ..................................................................................... 80 
 
Concomitant Therapy ....................................................................................... 80 
7 
Discontinuation/ Withdrawal Criteria ........................................................................... 81 
 
Discontinuation of Study Treatment ............................................................... 81 
 
Withdrawal from the Study ............................................................................. 81 
 
Patient Replacement ......................................................................................... 82 
 
Premature Termination of the Study .............................................................. 82 
8 
Study Assessments and Procedures ............................................................................... 83 
 
Informed Consent, Screening, and Enrollment .............................................. 83 
 
Informed Consent Requirements by Study Phase ................................. 84 
 
Medical History and Demographics ................................................................ 84 
 
Safety Assessments ............................................................................................ 84 
 
Physical Examinations, Height and Weight.......................................... 84 
 
Vital Signs ............................................................................................. 84 
 
Electrocardiograms ............................................................................... 85 
8.3.3.1 
Eastern Cooperative Oncology Group Performance  
Status .................................................................................... 85 
 
Tumor Tissue ..................................................................................................... 85 
 
Archival Tissue ..................................................................................... 85 
 
Procedures for Fresh Biopsy ................................................................. 86 
 
Clinical Safety Laboratory Assessments ......................................................... 86 
 
Efficacy Assessments ......................................................................................... 87 
 
Tumor Assessment ................................................................................ 87 
 
Pregnancy ........................................................................................................... 87 
 
Pregnancy Testing ................................................................................. 87 
 
Pregnancy on Study .............................................................................. 88 
 
Pharmacokinetics .............................................................................................. 88 
 
Pharmacodynamics ........................................................................................... 89 
 
Immunogenicity Assessments ........................................................................... 89 
 
Predictive and Pharmacodynamic Biomarkers .............................................. 90 

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Analysis of B7-H4 Expression.............................................................. 90 
 
Tumor Marker 
 ................................................. 91 
 
Gene Expression Profiling .................................................................... 92 
 
Adverse Events .................................................................................................. 93 
 
Method of Detecting and Reporting Adverse Events and Serious 
Adverse Events ..................................................................................... 93 
 
Adverse Event Definitions .................................................................... 93 
 
Assessment of Adverse Events ............................................................. 94 
8.12.3.1 Serious Adverse Events........................................................ 94 
8.12.3.2 Intensity (Severity) ............................................................... 95 
8.12.3.3 Causality ............................................................................... 96 
8.12.3.4 Outcome and Action Taken ................................................. 97 
 
Follow-up of Adverse Events and Serious Adverse Events ................. 97 
 
Treatment of Overdose ......................................................................... 97 
8.12.5.1 FPA150 ................................................................................ 97 
8.12.5.2 Pembrolizumab .................................................................... 98 
 
Regulatory Reporting Requirements for Serious Adverse Events ........ 98 
 
Concomitant Medication Recording ................................................................ 99 
 
End of Treatment Follow-Up ........................................................................... 99 
 
Long-Term Follow-Up........................................................................ 100 
9 
Statistical Considerations .............................................................................................. 101 
 
Sample Size Determination ............................................................................ 101 
 
Populations for Analyses ................................................................................ 102 
 
General Considerations .................................................................................. 103 
 
Statistical Analyses .......................................................................................... 103 
 
Safety Analyses ................................................................................... 103 
 
Efficacy Analyses ............................................................................... 103 
 
Pharmacokinetic Analyses .................................................................. 104 
 
Immunogenicity Analyses .................................................................. 104 
 
Pharmacodynamic Analyses ............................................................... 105 
 
Interim Analyses ................................................................................. 105 
10 Ethical, Legal, and Administrative Aspects ................................................................ 106 
 
Data Quality Assurance .................................................................................. 106 
 
Electronic Case Report Forms and Source Documentation ........................ 106 
 
Access to Source Data ..................................................................................... 106 

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Data Processing ............................................................................................... 107 
 
Archiving Study Records ................................................................................ 107 
 
Good Clinical Practice .................................................................................... 108 
 
Informed Consent ............................................................................................ 108 
 
Protocol Approval and Amendment .............................................................. 108 
 
Clinical Study Report and Publications ........................................................ 108 
 Confidentiality ................................................................................................. 109 
 Other Ethical and Regulatory Issues ............................................................. 109 
11 References ....................................................................................................................... 110 
12 Appendices ...................................................................................................................... 112 
 
LIST OF TABLES 
Table 1: 
Objectives and Endpoints: Phase 1a ................................................................. 49 
Table 2: 
Objectives and Endpoints: Phase 1b ................................................................. 51 
Table 3:  
Proposed Dose Levels for Phase 1a FPA150 Monotherapy ............................. 58 
Table 4: 
Proposed Dose Cohort/Levels for Phase 1a Combination Safety Lead-in 
(FPA150 in Combination with Pembrolizumab) .............................................. 59 
Table 5:  
Phase 1a Algorithm for FPA150 Monotherapy Dose-Escalation Decisions .... 61 
Table 6: 
Algorithm for Dose De-Escalation Decisions for FPA150 Safety Lead-In 
in Combination with Pembrolizumab in Phase 1a ............................................ 62 
Table 7: 
Proposed Dose Cohort/Level for Phase 1a Dose Exploration .......................... 63 
Table 8:  
Phase 1b Expansion Cohorts and Tumor Types ............................................... 63 
Table 9: 
Study Treatment Regimen of Combined Treatment of FPA150 and 
Pembrolizumab ................................................................................................. 75 
Table 10: 
Dose Modification Guidelines for FPA150 (Non-infusion Toxicity)............... 77 
Table 11: 
Two-Sided 90% Confidence Intervals of the Observed Response Rates ....... 102 
Table 12: 
Schedule of Assessments: Phase 1a and Phase 1b (Monotherapy and 
Combination Cohorts) ..................................................................................... 113 
Table 13: 
Schedule of Pharmacokinetic, Immunogenicity, and Pharmacodynamic 
Blood Sample Collection ................................................................................ 117 
Table 14: 
Eastern Cooperative Oncology Group Performance Status ............................ 120 
Table 15: 
Clinical Laboratory Tests ................................................................................ 121 
Table 16: 
New York Heart Association Classification ................................................... 123 
Table 17: 
Document History ........................................................................................... 125 
 

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LIST OF FIGURES 
Figure 1: 
Tumor Growth Inhibition in CT26 Engineered to Express B7-H4 Protein ...... 42 
Figure 2: 
Combination of anti-B7-H4 and anti-Programmed Death 1 in 4T1 
Engineered to Express B7-H4 Protein .............................................................. 43 
Figure 3: 
Study Schema- Monotherapy ............................................................................ 57 
Figure 4: 
Study Schema - Combination ........................................................................... 57 
 
 
 

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List of Abbreviations and Definitions 
Abbreviation 
Definition 
ADA 
anti-drug antibody 
ADCC 
antibody-dependent cell-mediated cytotoxicity 
AE 
adverse event 
AIDS 
acquired immunodeficiency syndrome  
ALT 
alanine transaminase  
ANC 
absolute neutrophil count  
APCs 
antigen presenting cells 
APTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase  
AUC 
area under serum concentration-time curve  
AUC0-7days 
AUC weekly exposure 
β-hCG 
β-human chorionic gonadotropin  
B7-H4 
transmembrane protein of the B7 family, also known as VTCN1 
BUN 
blood urea nitrogen 
C1D1 
Cycle 1 Day 1 
CBC 
complete blood count 
CEA 
carcinoembryonic antigen 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CK 
creatinine kinase 
CL 
clearance  
Cmax 
maximum observed serum concentration/ maximum concentration  
CNS 
central nervous system  
Combo 
combination 
CR 
complete response 
CRC 
Cohort Review Committee 
CrCl 
creatinine clearance  
CRF 
case report form  
CRO 
contract research organization 
CT 
computed tomography  
CTA 
clinical trial agreement 
CTCAE 
Common Terminology Criteria for Adverse Events  
CTLA-4 
cytotoxic T-lymphocyte-associated protein 4 
Ctrough 
trough serum concentration at the end of a dose interval 
DILI 
Drug-induced Liver Injury 
DLT 
dose-limiting toxicity 
DOR 
duration of response  

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Abbreviation 
Definition 
ECG 
electrocardiogram  
ECOG 
Eastern Cooperative Oncology Group  
eCRF 
electronic case report form 
ELISA 
enzyme linked immunosorbent assay  
EOT 
End of Treatment 
ER 
estrogen receptor 
eSAE Form 
Electronic Serious Adverse Event Form 
FDA 
Food and Drug Administration 
FFPE 
formalin-fixed paraffin-embedded; 
FcγIIIa 
Fcγ receptor IIIa 
GCP 
Good Clinical Practices  
GI 
gastrointestinal 
GLP 
Good Laboratory Practices 
GTT 
Gamma-glutamyl transferase  
Hb 
Hemoglobin 
HbcAb 
hepatitis B core antibody 
HBsAg 
hepatitis B virus surface antigen  
HCV 
hepatitis C virus 
HEK293 
human embryonic 293 cells 
HER2 
human epidermal growth factor receptor 2 
HIV 
human immunodeficiency virus  
HPV 
human papilloma virus 
HR+ 
hormone receptor positive 
HU IgG 
human immunoglobulin G 
IB 
Investigator’s Brochure  
ICF 
informed consent form  
ICH 
International Conference on Harmonization  
IEC 
Independent Ethics Committee  
IHC 
Immunohistochemistry 
IgG 
immunoglobulin G 
IND 
investigational new drug (application) 
IFNγ 
interferon gamma 
IL 
interleukin 
INR 
international normalized ratio  
IP 
investigational product (FPA150 or placebo) 
irAE 
immune-related adverse event 
IRB 
Institutional Review Board  
IV 
intravenous 

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Abbreviation 
Definition 
LDH 
lactate dehydrogenase 
LTFU 
long-term follow-up 
MDSC 
myeloid derived suppressor cells 
MRI 
magnetic resonance imaging  
msIgG 
mouse IgG 
MTD 
maximum tolerated dose  
NCA 
non-compartment(al) analysis 
NCI 
National Cancer Institute 
NK 
natural killer cells 
NFAT-Res 
Nuclear Factor Activated T cells responsive elements (RBL2H3-NFAT-
Re cell line) 
NOAEL 
no-observed-adverse-effect level 
NCA 
non-compartmental analysis 
NYHA 
New York Heart Association 
ORR 
overall response rate  
OS 
overall survival  
PBMC(s) 
peripheral blood mononuclear cell(s) 
PD 
progressive disease 
PD1 
programmed death 1 
PD-L1 
programmed death ligand 1 
PD-L2 
program death ligand 2 
PFS 
progression-free survival  
PK 
pharmacokinetic(s)  
PR 
partial response  
PT 
prothrombin time 
PTT 
partial thromboplastin time 
Q3W 
once every 3 weeks  
Q12W 
once every 12 weeks 
QTc 
QT interval corrected for heart rate 
RBC 
red blood cell 
RD 
recommended dose  
RECIST 
Response Evaluation Criteria in Solid Tumors 
RNA 
ribonucleic acid 
RNAseq 
ribonucleic acid sequencing 
SAE 
serious adverse event 
SAP 
statistical analysis plan  
SD 
standard deviation  
t1/2 
terminal half-life  
TB 
tuberculosis 

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Abbreviation 
Definition 
TEAE 
treatment-emergent adverse event 
TK 
toxicokinetics 
TNBC 
triple negative breast cancer/triple negative breast carcinoma 
ULN 
upper limit of normal  
VEGF 
vascular endothelial growth factor 
Vss 
volume of distribution at steady state 
 
 

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2 
Introduction 
B7-H4 (a transmembrane protein of the B7 family also known as B7S1, B7x, or VTCN1) is a 
negative regulator of T cell function. It is expressed on antigen presenting cells (APCs) and 
binds to an unknown receptor on activated T cells. While there is limited expression in normal 
tissues, there is high level of aberrant expression on the cell surface of a number of tumor 
types, particularly breast and gynecological cancers. This high expression is correlated with 
poor outcomes in several tumors, including breast, ovarian, and endometrial carcinoma  
(He 2011, Fan 2014, Liu 2014, Miyatake 2007, Simon 2007, Kryczek 2007). FPA150 is a 
fully human Immunoglobulin G1 (IgG1) kappa monoclonal antibody targeting B7-H4 that is 
being developed for the treatment of malignancies that express high levels of B7-H4 protein.  
Recent immuno-oncology approaches have focused on reprogramming the immune system to 
mount an effective response against tumors that have evaded the initial immune response. 
Specifically, blocking antibodies against both the programmed death 1/ programmed death 
ligand 1 (PD1/PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) axes have 
been effective in re-invigorating anti-tumor immunity, resulting in improved progression-free 
survival (PFS) and overall survival (OS) in some patients. However, responses have only been 
observed in select tumor types, and even in these tumor types only a subset of patients show 
durable responses to checkpoint inhibitors. Breast and gynecological tumors are examples of 
tumor types where checkpoint inhibitors have demonstrated limited activity thus far 
(Hamanishi 2015). 
Similar to other checkpoint molecules, when tumor cells expressing B7-H4 encounter 
activated T cells expressing the B7-H4 counter receptor, anti-tumor immunity is dampened. 
One therapeutic strategy for increasing anti-tumor immunity is to inhibit the interaction 
between B7-H4 on tumor cells with its counter receptor expressed on activated T cells, thus 
restoring anti-tumor immunity. This strategy could be effective in tumor types in which 
PD-L1 is not expressed or expressed alongside B7-H4, and it could thus provide efficacy on 
its own or in combination with PD1 pathway inhibitors, respectively. 
In addition to checkpoint inhibition, a potential therapeutic strategy for targeting tumors with 
high B7-H4 expression is to promote direct tumor cell killing via antibody-dependent 
cell-mediated cytotoxicity (ADCC). FPA150 is an IgG1 antibody that has been engineered 
with an Fc domain with high affinity for the Fcγ receptor IIIa (FcγIIIa) present on natural 
killer (NK) cells and macrophages. Antibody recognition of B7-H4 on tumor cells would lead 
to enhanced recruitment of NK cells and macrophages and enhanced ADCC.  
FPA150 is a fully human IgG1 kappa monoclonal antibody specific for B7-H4 that has been 
designed to comprise both T cell immune checkpoint blockade and ADCC activity. FPA150 is 
being developed for the treatment of patients with solid tumors that express high levels of 
B7-H4.  

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Study Rationale 
B7-H4 is highly expressed in a variety of solid tumors including breast carcinoma, ovarian 
carcinoma, endometrial carcinoma, and bladder carcinoma (He 2011, Fan 2014, Liu 2014, 
Miyatake 2007, Simon 2007, Kryczek 2007). 
 
 
 
B7-H4 appears to be an ideal target for the development of a therapeutic antibody 
given its high expression pattern in solid tumors compared to normal tissue, negative 
correlation with patient outcomes, and its role as a T cell checkpoint. FPA150, a fully human 
IgG1 antibody targeting B7-H4 is being developed for testing in patients with advanced solid 
tumors types that express high levels of B7-H4. To the best of our knowledge, this is the first 
human trial of any molecule targeting this pathway. In vitro studies indicated that FPA150 
may inhibit tumor growth through ADCC and T cell immune checkpoint inhibition. FPA150 
demonstrated, dose-dependent anti-tumor activity in syngeneic mouse cancer models that 
were engineered to express the B7-H4 protein, both as monotherapy and in combination with 
an anti-PD1 antibody.  
This study (Study Title: A Phase 1a/1b Study of FPA150, an Anti-B7-H4 Antibody, in 
Patients with Advanced Solid Tumors) is a Phase 1a/1b open-label, multicenter, study to 
evaluate the dosing, safety, tolerability, pharmacokinetic (PK), pharmacodynamics, and 
preliminary efficacy of FPA150 as a monotherapy and in combination with pembrolizumab, 
in patients with advanced solid tumors. The study includes Phase 1a Dose Escalation, Phase 
1a combination safety lead-in, Phase 1a Dose Exploration, and Phase 1b Dose Expansion for 
FPA150 monotherapy and in combination with pembrolizumab in patients with specific tumor 
types whose tumors overexpress B7-H4. After identification of the maximum tolerated dose 
(MTD) and/or recommended dose (RD), preliminary efficacy will be evaluated in planned 
expansion cohorts in specific tumor types based on the known levels of B7-H4 over-
expression. The planned Phase 1b tumor types include advanced/ metastatic breast cancer, 
ovarian cancer, and endometrial cancer. Despite recent advances in immunotherapy, 
significant unmet need remains for these recurrent or metastatic tumor types that express 
B7-H4. Sequential single agent chemotherapy is common in metastatic breast carcinoma, 
particularly after failure of endocrine therapy (in hormone-receptor positive patients) and 
human epidermal growth factor receptor 2 (HER2)-directed therapy (in HER2-positive 
patients). Patients with triple negative breast cancer (TNBC) and patients that have failed 
targeted therapy have a particularly poor prognosis. Metastatic breast cancer patients that had 
failed at least one prior chemotherapy and subsequently received capecitabine had a median 
time to progression of 4.9 months and a median OS of 15.2 months (Fumoleau 2004). The 
median PFS and OS is generally consistent across multiple trials with other chemotherapeutic 
agents in heavily pretreated patients (Cortes 2011, Martin 2007). TNBC patients who had 
received at least one prior chemotherapy and treated with pembrolizumab, a PD1 
immunotherapy, had a median PFS of 1.9 months and overall response rate (ORR) of less than 

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5% irrespective of PD-L1 status (Adams 2017). The combination of atezolizumab and nab-
paclitaxel in frontline metastatic TNBC patients showed improvement in median OS 
compared to nab-paclitaxel alone. However the benefit was predominatly observed in PD-L1 
positive patients (HR 0.62) compared to all patients (HR 0.84) suggesting low efficacy in 
PD-L1 negative patients (Schmid 2018).  Patients with recurrent or metastatic endometrial 
carcinoma who experience progressive disease on frontline chemotherapy have a poor 
prognosis with median OS of less than 1 year. For example, patients treated with the anti-
vascular endothelial growth factor (VEGF)-A monoclonal antibody bevacizumab after failure 
of 1 or 2 lines of chemotherapy reported a median PFS of 4.2 months and median OS of 10.5 
months (Aghajanian 2011). Patients with early platinum-refractory, recurrent or metastatic 
ovarian cancer have a median OS of 13 to 16 months and median PFS of 3 to 6 months with 
single agent chemotherapy with or without bevacizumab (Pujade-Lauraine 2014). Median 
PFS and OS significantly diminish in patients with multiply relapsed disease (Hanker 2012). 
Immunotherapy has demonstrated limited activity to date in this tumor type (Hamanishi 2015). 
Therefore, significant unmet need still exists in these tumor types  particularly in the 
metastatic setting after failure of standard frontline therapy. 
 
Background 
 
50, an Anti-B7-H4 Antibody 
FPA150 is a fully human IgG1 kappa monoclonal antibody targeting B7-H4 that is being 
developed for the treatment of malignancies that express high levels of B7-H4. FPA150 is an 
antibody designed to recognize B7-H4 when expressed on surface membrane of tumors. 
B7-H4 can be highly expressed in certain types of tumor without known genetic aberrations. 
FPA150 has been glycoengineered for high affinity binding to the FcγRIIIa receptor and can 
potentially induce ADCC against tumor cells with high B7-H4 expression. FPA150 may also 
block B7-H4-mediated inhibition of T cell proliferation and interferon gamma (IFNγ) 
production. Therefore, FPA150 has the potential to demonstrate anti-tumor immune responses 
in patients with B7-H4-high tumors by providing both ADCC and T cell immune checkpoint 
blockade activities. 
 
Nonclinical Pharmacology Studies with FPA150 
FPA150 has 2 potential mechanisms of action: It acts as a T cell checkpoint inhibitor by 
blocking B7-H4 inhibition of T cell proliferation and IFNγ production, and it induces ADCC 
against tumor cells. Both of these mechanisms were explored in vitro and in vivo. 
2.2.2.1 
In Vitro Biology 
Both T cell immune checkpoint blockade activity and ADCC of FPA150 were determined by 
in vitro assays as summarized below. 

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The ability of FPA150 to overcome B7-H4-mediated inhibition of IFNγ production was 
determined using a co-culture system. There were 2 cell types employed in the co-culture 
system: 1) human embryonic 293 cells (HEK293) cells (which were engineered to be artificial 
antigen presenting cells, by expressing both a single chain version of the CD3 activator 
antibody OKT3 and B7-H4), and 2) primary human T cells. In the co-culture system, the 
HEK293 cells were incubated with the primary human T cells and treated with FPA150. 
Upon co-culture, IFNγ was significantly increased in the presence of FPA150 in comparison 
to human IgG1 isotype-treated cells, suggesting that FPA150 functionally blocks B7-H4-
mediated suppression of IFNγ production from primary human T cells and that FPA150 may 
act as a T cell checkpoint inhibitor in patients.  
In vitro, ADCC was demonstrated using IL-2 activated peripheral blood mononuclear cells 
(PBMCs) as the effector cells and SKBR-3 human breast cancer cells, which endogenously 
express B7-H4, as the target cells. FPA150 treatment led to a dose-dependent increase in 
ADCC, and this effect was > 61 fold more potent than ADCC performed with a 
non-glycoengineered version of FPA150. To determine the relationship between B7-H4 
receptor cell surface density and FPA150-mediated ADCC activity, Jurkat cells transduced to 
expresses human FcγRIIIA and an Nuclear Factor Activated T cells responsive elements 
(NFAT-Res) luciferase-reporter, were co-cultured with target cells endogenously expressing 
varying levels B7-H4 on the cell surface (~15,000 to ~340,000 molecules/ cell). Maximal 
ADCC activity correlated with the number of receptors, increasing almost 5-fold from the 
lowest expressing cells to the highest expressing cells, suggesting that the strongest ADCC 
activity may be seen in patients whose tumors express the highest levels of B7-H4.  
2.2.2.2 
In Vivo Pharmacology 
Unlike human tumors, mouse models do not endogenously express high levels of B7-H4 
protein. To test FPA150 in mice, syngeneic mouse cancer models using murine tumor cell 
lines engineered to express B7-H4 protein were used. These cancer models express moderate 
to high levels of the B7-H4 protein on their cell surface and demonstrate significant tumor 
growth suppression upon treatment with FPA150, though because they are engineered models 
they may not be as sensitive to FPA150 as humans. A dose response study (twice weekly 
dosing) was performed with a sensitive model, a mouse colon cancer cell line, CT26, which 
grows in immune competent mice. Propagating this model in a wild-type mouse allows for the 
presence of intact tumor-immune interactions, thereby allowing the assessment of FPA150 
against the tumor cells directly and in modulating the host immune system to more potently 
suppress tumor growth. 
The engineered CT26 model expressing B7-H4 protein demonstrated significant dose-
dependent tumor growth inhibition in 5 dose levels in the dose range from 1 to 30 mg/kg 
(Figure 1). The most common impact in individual animals was tumor growth inhibition. 
However, FPA150 treatment did result in complete tumor regression in 7 of 15 mice in the 
30 mg/kg group, 6 of 15 mice in the 20 mg/kg group, and 5 of 15 mice in the 10 mg/kg group. 

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FPA150 dosed at 3 mg/kg or lower elicited minimal anti-tumor activity compared to the 
negative control treatment group (human IgG).  
Figure 1: 
Tumor Growth Inhibition in CT26 Engineered to Express B7-H4 Protein 
0
5
1 0
1 5
2 0
0
2 0 0
4 0 0
6 0 0
8 0 0
1 0 0 0
1 2 0 0
D a y s  p o s t  i n o c u l a t i o n
T u m o r  V o l u m e
( M e a n  m m
3 ± S D )
F P A 1 5 0
H u  I g G
1  m g / k g
3  m g / k g
1 0  m g / k g
2 0  m g / k g
3 0  m g / k g
c m F P A 1 5 0 - F
 
Abbreviations: B7-H4 = transmembrane protein of the B7 family; Hu IgG = human immunoglobulin G; 
SD = standard deviation. 
 
In addition, the efficacy of cmFPA150-F (anti-B7-H4 mouse IgG [msIgG]2a, fucosylated) and 
anti-PD1 antibody was examined as single agent and in combination (Figure 2). In the tumor 
model that was utilized, human B7-H4 was engineered to be expressed on the tumor cell 
surface of the mouse breast cancer cell line, 4T1. The 4T1 cell line, which arose from and is 
propagated in immune competent mice, is known to be less sensitive to immune modulatory 
therapeutics. This study examined the anti-tumor efficacy of cmFPA150-F, of mouse 
anti-PD1 antibody, or of the combination (cmFPA150-F + anti-PD1). Monotherapy with 
either anti-B7-H4 antibody or anti-PD1 demonstrated similar, significant tumor growth 
reduction. Importantly, the combination of cmFPA150-F and anti-PD1 was significantly more 
potent than either monotherapy, with a significantly greater reduction in mean tumor volume 
as well as 6 of 12 mice demonstrating complete tumor regression, compared to 1 of 12 mice 
for anti-PD1, and 0 of 12 for cmFPA150-F. 

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Figure 2: 
Combination of anti-B7-H4 and anti-Programmed Death 1 in 4T1 
Engineered to Express B7-H4 Protein 
1 0
1 5
2 0
2 5
3 0
3 5
0
2 0 0
4 0 0
6 0 0
8 0 0
1 0 0 0
1 2 0 0
D a y s  p o s t  I n o c u l a t i o n
T u m o r  V o l u m e
( M e a n  m m
3 ±  S D )
m s I g G
c m F P A 1 5 0 - F
a n t i- P D - 1
C o m b o
c m F P A 1 5 0 - F
a n t i - P D - 1
 
Abbreviations: B7-H4 = transmembrane protein of the B7 family; Combo = combination; IgG = immunoglobulin 
G; msIgG = mouse IgG; PD1 = programmed death 1; SD = standard deviation. 
 
Mechanistically, FPA150 was developed to bind to B7-H4 on the tumor cell surface and elicit 
anti-tumor efficacy via ADCC and T cell checkpoint blockade. Although these tumor models 
are engrafted in immune competent mice, the mouse Fcγ receptors (the receptors on immune 
cells required for ADCC) have lower affinity for human antibodies than the human Fcγ 
receptors.  
 
Nonclinical Pharmacokinetics 
The PK/ toxicokinetics (TK) of FPA150 were evaluated following a single and/or repeat 
weekly intravenous (IV) administration in mice, rats, and cynomolgus monkeys. PK 
characteristics observed were consistent across all studies and similar to other mAbs in 
general. In all species, FPA150 demonstrated linear PK and a dose proportional increase in 
exposure (area under serum concentration-time curve [AUC]) with increasing dose. There was 
an approximate 2-fold increase in weekly exposure (AUC0-7days) following 4 weekly 
administrations of FPA150 between first and last dose, however, steady state was not 
achieved. No substantial gender differences were apparent in the serum FPA150 

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concentration-time profiles. In the cynomolgus monkey (across 2 different studies), half-life 
estimated from recovery animals only ranged from approximately 8.8 days to 12 days with 
doses levels ranging from 1 to 100 mg/kg. The estimated half-life in rat following a single IV 
infusion administration at 40 mg/kg was approximately 13.2 days. The PK characteristics of 
FPA150 in animals support IV infusion in humans with a once every 3 week (Q3W) dose 
regimen.  
 
Toxicology 
Toxicology studies with FPA150 have been performed in rat and cynomolgus monkey. 
The studies performed have included a pilot single dose PK/tolerability study in rats, a pilot 
repeat-dose toxicity study in cynomolgus monkeys and investigational new drug 
(IND)-enabling Good Laboratory Practices (GLP) repeat-dose toxicity studies in rats and 
cynomolgus monkeys, as well as a GLP tissue cross-reactivity study with human, rat, and 
cynomolgus monkey tissues.  
In the single dose pilot tolerability study in rats, the animals received doses up to 40 mg/kg as 
a 30-minute IV infusion. FPA150 had no effect on clinical observations, body weights, food 
consumption, clinical pathology (serum chemistry or hematology) assessments, gross 
observations, organ weights, or histopathology assessment.  
In the pilot repeat-dose toxicology study cynomolgus monkeys received 4 weekly IV doses of 
FPA150 up to 100 mg/kg as a 30-minute IV infusion. All doses were well tolerated by 
cynomolgus monkeys. There were no test article-related unscheduled mortalities or changes 
attributed to administration of FPA150 during assessment of clinical observations, body 
weights, clinical pathology, necropsy, organ weight, or histopathology parameters.  
In the repeat-dose GLP toxicology studies, FPA150 was administered by IV at dose levels of 
1, 10, or 100 mg/kg/dose to both rats and cynomolgus monkeys for 4 weekly doses. 
Reversibility of toxicity was evaluated during a 6-week recovery period following the final 
administration. Parameters for evaluation included ophthalmic examinations, clinical 
observations, body temperatures, body weights, food consumption, hematology, coagulation, 
clinical chemistry, urinalysis, organ weights, macroscopic, and microscopic evaluation. In the 
cynomolgus monkey study, electrocardiograms (ECGs) were also assessed to evaluate 
potential cardiac toxicities.  
During the evaluation of the GLP rat study, FPA150 was generally well tolerated and there 
were no toxic effects attributed to FPA150. The no-observed-adverse-effect level (NOAEL) in 
Sprague Dawley rats was considered to be 100 mg/kg/dose. 
In the GLP cynomolgus monkey study, FPA150 was generally well tolerated and there were 
no adverse events (AEs) attributed to FPA150 observed in any of the parameters evaluated. 
During the study, a higher incidence of diarrhea was observed at the end of the dosing phase 
in the higher dose groups. Due to the higher incidence of affected animals in the mid and high 

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dose, as well as onset in the later phase of the dosing period, a relationship with FPA150 
exposure is possible. There were no microscopic changes in the intestinal tract in animals 
treated with FPA150, including animals with diarrhea; therefore, this finding was considered 
non-adverse but possibly related to the test article. There was a single mortality in the study. 
One animal in the mid dose recovery group was found dead on Study Day 35, 14 days post the 
last dose. Clinical observations, macroscopic and microscopic evaluation were consistent with 
the diagnosis of intestinal torsion. Intestinal torsions occasionally occur in cynomolgus 
monkeys, and this was considered a spontaneous condition in this animal and not test 
article-related. The NOAEL in cynomolgus monkey was considered to be 100 mg/kg/dose. 
In addition to in vivo toxicology studies, a GLP-compliant tissue cross reactivity study has 
been performed to compare the binding of FPA150 to a panel of 36 tissues from rat, 
cynomolgus monkey, and human. The result showed that the binding pattern of FPA150 was 
similar among the 3 species and limited to the mammary gland epithelium. 
In summary FPA150 was well tolerated in cynomolgus monkey and rat. The NOAEL in both 
species was considered to be 100 mg/kg/dose, the highest dose tested when given as 4 weekly 
IV doses. 
 
Clinical Experience with FPA150 
This is a first-in-human clinical study and there is limited clinical experience with FPA150. 
2.2.5.1 
Study Population: 
25 patients with a variety of solid tumors have been enrolled in clinical trial FPA150-001 as 
of the data cut off date December 31, 2018: 19 patients unselected for B7-H4 expression  in 
Phase 1a Dose Escalation; 6 patients with B7-H4+ solid tumors in Phase 1a Dose Exploration.  
One patient in dose escalation was dosed but not included in the safety summary, so the safety 
data is based on 24 patients. 
2.2.5.2 
Patient Characteristics 
The 24 patients had a median age of 67.5 years (range 40, 84), 18 of 24 patients were female 
and 23 were white.  Most patients enrolled on the study had Stage III or IV cancer (n=22) with 
ovarian carcinoma being the most common tumor type (n=9).  Other common tumors 
included gallbladder/cholangiocarcinoma (n=4) and leiomyosarcoma (n=3).   
2.2.5.3 
Study Drug Exposure 
During Dose Escalation 18 patients received FPA150 across a range of dose levels from 
0.01 mg/kg to 20 mg/kg.  Two patients received FPA150 at the highest 20 mg/kg dose level 
prior to the data cutoff date while 2 additional patients have subsequently received FPA150 at 
that dose level and have completed their dose-limiting toxicity (DLT)) review period.   Dose 
Exploration patients received FPA150 at 3 mg/kg (n=5) and 10 mg/kg (n=1).  Median number 
of doses in phase 1a (dose escalation and exploration) was 3 (range 1,11) and median 

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exposure was 63 days (range 21,233).  No dose reductions were required, and the median dose 
intensity was 100%.   
2.2.5.4 
Dose Limiting Toxicities: 
No dose limiting toxicities (DLTs) have been identified in patients enrolled in the dose 
escalation cohorts in FPA150-001 at any dose level up to 20 mg/kg.. 
2.2.5.5 
Adverse Events: 
As of 31 Dec 2018, 20 of 24 patients enrolled on FPA150-001 have experienced at least one 
treatment emergent adverse event (TEAE).  The most frequently reported TEAEs  include 
fatigue (n=6) followed by nausea, diarrhea, abdominal pain, decreased appetite, and decreased 
albumin (n=4 patients): 
Eight  of 24 patients enrolled on FPA150-001 experienced at least one Grade 3-4 TEAEs with 
abdominal pain reported in 2 patients being the most common.  .  One patient with 
cholangiocarcinoma had a Grade 5 AE of acute kidney injury, which was assessed by the 
investigator as unrelated to study drug and occurred in the setting t of disease progression.   
Treatment related AEs (TRAEs) as determined by the investigator were reported in 14 of 
24 patients, most of which were grades 1 and 2.  Diarrhea and fatigue were the most common 
TRAEs reported in 4 patients each.  One Grade 3 TRAE of hypertension was reported among 
24 patients.  
2.2.5.6 
Serious Adverse Events 
Three  of 24 patients enrolled on FPA150-001 have experienced at least 1 serious adverse 
event (SAE).  These events included a grade 3 intestinal obstruction, a grade 3 hypokalemia 
and a grade 5 acute kidney injury.   
None of the SAEs in  patients treated with FPA150-001 were assessed as related to treatment.  
One  of the 3 patients with SAEs was treated at a dose of 0.01 mg/kg, one at 1 mg/kg and one 
at 10 mg/kg.   
2.2.5.7 
Deaths 
Study FPA150-001  accrued a patient population with advanced solid tumors for which 
standard curative or palliative measures did not exist or were no longer effective.  As of 
31 December 2018, one on study death was reported in study FPA150-001.  The  patient 
treated at 10 mg/kg died of acute kidney injury (not related to FPA150) in the setting of 
underlying disease progression.    
 
Pembrolizumab Background 
The PD-1 ligand-receptor interaction is one of the most signficant immune checkpoint 
pathways sequestered by tumor cells to escape T-cell mediated immune surveillance. 

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Pembrolizumab is a humanized IgG4 mAb with specificity of binding to the programmed cell 
death 1 (PD1) receptor, thus inhibiting its interaction with programmed cell death ligand 1 
(PD-L1) and programmed cell death ligand 2 (PD-L2).  Keytruda® (pembrolizumab) is 
indicated for the treatment of patients with  non-small cell lung cancer, melanoma, urothelial 
carcinoma, and head and neck cancer. Refer to the Keytruda® (pembrolizumab) Prescribing 
Information (Keytruda® USPI) for additional information.  
 
Rationale for Combination with Pembrolizumab 
FPA150 has two potential mechanisms of action: it acts as a T cell checkpoint inhibitor by 
blocking B7-H4 inhibition of T cell proliferation and IFNγ production, and it induces ADCC 
against tumor cells. As previously discussed, administration of FPA150 to patients whose 
tumors do not express PD1 may prove to be an effective strategy. Additionally, there is the 
possibility that the administration of two checkpoint inhibitors would be synergistic. This 
hypothesis was explored on an in vivo model examining the anti-tumor efficacy of 
cmFPA150-F (a mouse surrogate of FPA150), of mouse anti-PD1 antibody, or of the 
combination (cmFPA150-F + anti-PD1). Monotherapy with either anti-B7-H4 antibody or 
anti-PD1 demonstrated similar, significant tumor growth reduction. Importantly, the 
combination of cmFPA150-F and anti-PD1 was significantly more potent than either 
monotherapy, with a significantly greater reduction in mean tumor volume as well as 6 of 
12 mice demonstrating complete tumor regression, compared to 1 of 12 mice for anti-PD1, 
and 0 of 12 for cmFPA150-F (Figure 2). These findings suggest that exploring the 
combination may be a viable strategy in a variety of tumors. In tumors where anti-PD1 agents 
have demonstrated efficacy and that co-express B7-H4 and PD1, administering the 
combination of FPA150 and an anti-PD1 antibody may further enhance the antitumor activity 
of anti-PD1 agents (e.g. TNBC; (Schmid 2018)). In addition, some of the tumors that are 
known to express B7-H4 at a high level [eg ovarian, ER+ breast and micro-satellite stable 
(MSS) endometrial cancer] have demonstrated limited responses to anti-PD1 agents so far and 
the combination may lead to a potential role for immune-oncology therapies in these tumors.     
 
Benefit/ Risk Assessment  
This overview is not intended to replace the complete information presented in the FPA150 
IB. Please consult the IB for more detailed information.  
This first in human study is currently ongoing to evaluate the dosing, safety, tolerability, PK 
and clinical activity of FPA150.  The phase 1a dose escalation included an accelerated 
titration design followed by a standard 3+3 design across 8 dose levels. The starting dose of 
0.01 mg/kg was selected based on MABEL calculations.  While clinical experience with 
FPA150 is currently limited, data from 25 patients dosed to date show that FPA150 
monotherapy is well tolerated at doses as high as 20 mg/kg with no DLTs. There have been no 
reports of FPA150-related grade 4 AEs or SAEs (including deaths).    

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FPA150 also demonstrated a favorable safety profile in animal studies with no toxic effects 
attributed to FPA150 being observed following 4 weekly doses. As noted in Section 2.2.4, in 
the GLP cynomolgus monkey study, a higher incidence of diarrhea was observed at the end of 
the dosing phase in the higher dose groups. Although the higher incidence of diarrhea in the 
cynomolgus monkey study was not considered adverse, and was without microscopic 
correlates, monitoring of patients in study FPA150-001 for diarrhea/enteritis will be 
conducted.  
The proposed expansion cohorts in Phase 1b after determination of the MTD and/or RD have 
been rationally selected based on the presence of B7-H4 expression across various tumor 
types. Preclinical data support specific targeting of tumors with high B7-H4 expression. 
Despite recent advances in targeted and immunotherapy, significant unmet need remains for 
the tumor types being proposed for evaluation in Phase 1b such as advanced breast cancer, 
ovarian cancer, and endometrial cancer. Targeting B7-H4 with FPA150, which possesses dual 
T cell checkpoint blockade and ADCC activity, is a viable approach in these patients with 
limited treatment alternatives.  
A strong mechanistic rationale supported by preclinical data exists for combining FPA150 
with pembrolizumab (Section 2.2.7).  Given the underlying mechanisms of action of both 
drugs (ie, immune checkpoint blockade) there is a potential to observe increased incidence of 
immune-mediated AEs with the combination.  However, it should be noted that in the  
25 patients treated with FPA150 monotherapy there have not been any reports of immune-
mediated toxicities.   
As this is the first clinical study of FPA150, the safety profile in humans has not yet been 
established, and unanticipated side effects may occur. Close monitoring of safety is planned in 
this study in order to limit the risk to patients. 
 
 

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3 
Objectives and Endpoints 
 
Phase 1a Objectives and Endpoints  
The objectives and endpoints for Phase 1a of the study are summarized in Table 1. Additional 
information regarding study assessments and procedures is provided in Section 8; statistical 
analysis information is provided in Section 9. 
Table 1: 
Objectives and Endpoints: Phase 1a 
OBJECTIVES 
ENDPOINTS 
PRIMARY - SAFETY 
FPA150 Monotherapy  
• To evaluate the safety and tolerability of FPA150 
as monotherapy in patients with advanced solid 
tumors treated at the  MTD and/or RD 
• To determine the MTD and/or RD of FPA150 
FPA150 Monotherapy 
• The incidence of Grade 3 and Grade 4 AEs and 
clinical laboratory abnormalities defined as DLTs 
• The incidence of AEs, clinical laboratory 
abnormalities, and ECG abnormalities 
FPA150 in Combination with Pembrolizumab 
• To evaluate the safety and tolerability of FPA150 
in combination with pembrolizumab in patients 
with B7-H4+ ovarian cancer 
• To determine the MTD and/or RD of FPA150 in 
combination with pembrolizumab in patients with 
B7-H4+ ovarian cancer 
FPA150 in Combination with Pembrolizumab 
• The incidence of AEs, clinical laboratory 
abnormalities, and ECG abnormalities 
• The incidence of Grade 3 and Grade 4 AEs and 
clinical laboratory abnormalities defined as DLTs 
SECONDARY - PHARMACOKINETIC 
FPA150 Monotherapy  
• To characterize the PK profile of FPA150 as 
monotherapy in patients with advanced solid 
tumors treated at the MTD and/or RD 
FPA150 Monotherapy  
• AUC 
• Maximum serum concentration (Cmax) 
• Trough serum concentration at the end of a dose 
interval (Ctrough) 
• Clearance (CL) 
• Termina half-life (t1/2) 
• Volume of distribution at steady state (Vss) 
• Other parameters, such as dose proportionality, 
accumulation ratio, attainment of steady state, 
will also be calculated if the data are available 
SECONDARY - IMMUNOGENICITY 
 
FPA150 Monotherapy 
• To characterize the immunogenicity of FPA150 as 
monotherapy in patients with advanced solid 
tumors treated at the MTD and/or RD 
FPA150 Monotherapy 
• Immune response (ADAs) to FPA150 

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OBJECTIVES 
ENDPOINTS 
EXPLORATORY - EFFICACY 
FPA150 Monotherapy 
• To evaluate the clinical benefit of FPA150 as 
monotherapy  
FPA150 Monotherapy 
• ORR defined as the total number of patients with 
confirmed responses of either CR or PR per 
Response Evaluation Criteria in Solid Tumors 
(RECIST) v1.1 divided by the total number of 
patients who are evaluable for a response 
• Duration of response (DOR), defined as the time 
from onset of response (CR or PR) that is 
subsequently confirmed to the first observation of 
progressive disease or death due to any cause 
• Progression free-survival (PFS), defined as the 
time from the patient’s first dose to the first 
observation of progressive disease or death 
FPA150 in Combination with Pembrolizumab 
• To evaluate the clinical benefit of FPA150 in 
combination with pembrolizumab in patients with 
B7-H4+ ovarian cancer 
FPA150 in Combination with Pembrolizumab 
• ORR, defined as the total number of patients with 
confirmed responses of either CR or PR per 
RECIST v1.1 divided by the total number of 
patients who are evaluable for a response 
• DOR, defined as the time from onset of response 
(CR or PR) that is subsequently confirmed to the 
first observation of progressive disease or death 
due to any cause  
• PFS, defined as the time from a patient’s first 
dose to the first observation of progressive 
disease or death due to any cause. 
EXPLORATORY - Pharmacokinetics 
FPA150 in Combination with Pembrolizumab 
• To characterize the pharmacokinetic (PK) profile 
of FPA150 in combination with pembrolizumab in 
patients with B7-H4+ ovarian cancer 
FPA150 in Combination with Pembrolizumab 
The following PK parameters will be derived from 
concentration-time data for FPA150 in combination 
with pembrolizumab when appropriate and 
applicable: 
• AUC 
• Cmax 
• Ctrough 
• Clearance (CL) 
• t1/2 
• Vss 
• Other parameters, such as dose proportionality, 
accumulation ratio, attainment of steady state, 
will also be calculated if the data are available for 
FPA150 
• Cmax and Ctrough as well as accumulation ratio of 
Cmax and Ctrough for pembrolizumab may be 
calculated if the data are available 

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OBJECTIVES 
ENDPOINTS 
EXPLORATORY - Immunogenicity 
FPA150 in Combination with Pembrolizumab 
• To characterize the immunogenicity of FPA150 in 
combination with pembrolizumab in patients with 
B7-H4+ ovarian cancer  
FPA150 in Combination with Pembrolizumab 
• Immune response (ADAs) to FPA150 
• Immune response (ADAs) to pembrolizumab 
EXPLORATORY – Pharmacodynamic Biomarkers 
FPA150 Monotherapy  
• To characterize the pharmacodynamic profile of 
FPA150 through an analysis of the immune cell 
infiltrate in pre-treatment and on-treatment tumor 
biopsies  
• To characterize the pharmacodynamic profile of 
FPA150 through evaluation of exploratory 
biomarkers in peripheral blood samples  
FPA150 Monotherapy  
• Changes in markers of tumor immune infiltrate 
• 
• Changes in selected pharmacodynamic 
biomarkers in peripheral blood samples 
FPA150 in Combination with Pembrolizumab 
• To characterize the pharmacodynamic profile of 
FPA150 in combination with pembrolizumab 
through an analysis of the immune cell infiltrate in 
pre-treatment and on-treatment tumor biopsies 
• To characterize the pharmacodynamic profile of 
FPA150 in combination with pembrolizumab 
through evaluation of exploratory biomarkers in 
peripheral blood samples  
 
FPA150 in Combination with Pembrolizumab 
• Changes in markers of tumor immune infiltrate 
• 
• Changes in selected additional pharmacodynamic 
markers in peripheral blood in patients treated 
with FPA150 in combination with 
pembrolizumab 
 
Phase 1b Objectives and Endpoints 
The objectives and endpoints for Phase 1b of the study are summarized in Table 2. Additional 
information regarding study assessments and procedures is provided in Section 8; statistical 
analysis information is provided in Section 9. 
Table 2: 
Objectives and Endpoints: Phase 1b 
OBJECTIVES 
ENDPOINTS 
PRIMARY - SAFETY 
FPA150 Monotherapy  
• To evaluate the safety and tolerability of FPA150 
as monotherapy in patients with B7-H4+ 
advanced solid tumors treated at the MTD and/or 
RD 
FPA150 Monotherapy  
• The incidence of AEs, clinical laboratory 
abnormalities, and ECG abnormalities 

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OBJECTIVES 
ENDPOINTS 
FPA150 Combined with Pembrolizumab 
• To evaluate the safety and tolerability of FPA150 
in combination with pembrolizumab in selected 
patients with B7-H4+ ovarian cancer  treated at 
the MTD and/or RD 
FPA150 Combined with Pembrolizumab 
• The incidence of AEs, clinical laboratory 
abnormalities, and ECG abnormalities  in patients 
treated with FPA150 in combination with 
pembrolizumab 
SECONDARY - EFFICACY 
FPA150 Monotherapy  
• To evaluate the clinical benefit of FPA150 as 
monotherapy in patients with B7-H4+ advanced 
solid tumors treated at the MTD and/or RD 
FPA150 Monotherapy  
• ORR, defined as the total number of patients with 
confirmed responses of either CR or PR per 
RECIST v1.1 divided by the total number of 
patients who are evaluable for a response 
• DOR, defined as the time from onset of response 
(CR or PR) that is subsequently confirmed to the 
first observation of progressive disease or death 
due to any cause  
• PFS, defined as the time from the patient’s first 
dose to the first observation of progressive disease 
or death due to any cause) 
FPA150 in Combination with Pembrolizumab 
• To evaluate the clinical benefit of FPA150 in 
combination with pembrolizumab in patients with 
B7-H4 + ovarian cancer treated at the MTD 
and/or RD 
FPA150 in Combination with Pembrolizumab 
• ORR, defined as the total number of patients with 
confirmed responses of either CR or PR per 
Response Evaluation Criteria in Solid Tumors 
(RECIST) v1.1 divided by the total number of 
patients who are evaluable for a response to FPA 
150 combined with pembrolizumab 
• DOR, defined as the time from onset of response 
(CR or PR) that is subsequently confirmed to the 
first observation of progressive disease or death 
due to any cause to FPA150 combined with 
pembrolizumab 
• PFS, defined as the time from the patient’s first 
dose to the first observation of progressive disease 
or death due to any cause to FPA150 combined 
with pembrolizumab 
SECONDARY - PHARMACOKINETICS 
FPA150 Monotherapy 
• To characterize the PK profile of FPA150 as 
monotherapy in patients with B7-H4+ advanced 
solid tumors treated at the MTD and/or RD 
FPA150 Monotherapy 
• AUC 
• Cmax 
• Ctrough 
• CL 
• t1/2 
• Vss 
• Other parameters, such as accumulation ratio, 
attainment of steady state, will also be calculated if 
the data are available 

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OBJECTIVES 
ENDPOINTS 
SECONDARY - IMMUNOGENICITY 
FPA150 Monotherapy 
• To characterize the immunogenicity of FPA150 
as monotherapy in patients with B7-H4+ 
advanced solid tumors treated at the MTD and/or 
RD 
FPA150 Monotherapy 
• Immune response (ADAs) to FPA150 
EXPLORATORY - PHARMACOKINETICS 
FPA150 in Combination with Pembrolizumab 
• To characterize the PK profile of FPA150 in 
combination with pembrolizumab in patients with 
B7-H4+ ovarian cancer treated at the MTD and/or 
RD  
• To characterize the PK profile of pembrolizimab 
in combination with FPA150 in patients with 
ovarian cancer 
FPA150 in Combination with Pembrolizumab 
The following PK parameters will be derived from 
concentration-time data for FPA150 in combination 
with pembrolizumab when appropriate and 
applicable: 
• AUC 
• Cmax 
• Ctrough 
• CL 
• t1/2 
• Vss 
• Other parameters, such as accumulation ratio, 
attainment of steady state, will also be calculated if 
the data are available for patients treated with 
FPA150 combined with pembrolizumab 
• Cmax and Ctrough as well as accumulation ratio of 
Cmax and Ctrough for pembrolizumab may be 
calculated if the data are available 
EXPLORATORY - IMMUNOGENICITY 
FPA150 in Combination with Pembrolizumab 
• To characterize the immunogenicity of FPA150 
in combination with pembrolizumab in patients 
with B7-H4+ ovarian cancer treated at the MTD 
and/or RD 
• To characterize the immunogenicity of 
pembrolizumab in combination with FPT150 
patients with with B7-H4+ ovarian cancer  treated 
at the MTD and/or RD 
FPA150 in Combination with Pembrolizumab 
• Immune response (ADAs) to FPA150 
• Immune response (ADAs) to pembrolizumab 
EXPLORATORY – PHARMACODYNAMIC BIOMARKERS 
FPA150 Monotherapy 
• To characterize the pharmacodynamic profile of 
FPA150 through an analysis of the immune cell 
infiltrate in pre-treatment and on-treatment tumor 
biopsies  
• To characterize the pharmacodynamic profile of 
FPA150 through evaluation of exploratory 
biomarkers in peripheral blood samples  
FPA150 Monotherapy  
• Changes in markers of tumor immune infiltrate 
• 
• Changes in selected pharmacodynamic biomarkers 
in peripheral blood samples 

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OBJECTIVES 
ENDPOINTS 
FPA150 in Combination with Pembrolizumab 
• To characterize the pharmacodynamic profile of 
FPA150 in combination with pembrolizumab 
through an analysis of the immune cell infiltrate 
in pre-treatment and on-treatment tumor biopsies 
• To characterize the pharmacodynamic profile of 
FP150 in combination with pembroliumab 
through evaluation of exploratory biomarkers in 
peripheral blood samples  
FPA150 in Combination with Pembrolizumab 
• Changes in markers of tumor immune infiltrate, 
• 
• Changes in selected additional pharmacodynamic 
biomarkers in peripheral blood samples for 
patients treated with FPA150 in combination with 
pembrolizumab 
EXPLORATORY - EFFICACY 
FPA150 Monotherapy 
• To evaluate the clinical benefit of FPA150 as 
monotherapy in patients with B7-H4+ advanced 
solid tumors treated at the MTD and/or RD 
FPA150 Monotherapy 
• OS, defined as time from patient’s first dose to 
death due to any cause 
FPA150 in Combination with Pembrolizumab 
• To evaluate the clinical benefit of FPA150 in 
combination with pembrolizumab in patients with 
B7-H4+ ovarian cancer treated at the MTD and/or 
RD 
FPA150 in Combination with Pembrolizumab 
• OS, defined as time from patient’s first dose to 
death due to any cause 
 
 

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4 
Study Design  
 
Overall Design 
The Study Schema is provided below in Figure 3.  
This is a Phase 1a/1b open-label, multicenter study to evaluate the dosing, safety, tolerability, 
PK, pharmacodynamics, and preliminary efficacy of FPA150 as monotherapy and in 
combination with pembrolizumab, an anti-PD1 antibody, in patients with advanced solid 
tumors.  
There will be approximately 6 to 10 study centers participating in Phase 1a in the United 
States and approximately 35 study centers participating in Phase 1b. Phase 1a and the 
combination cohorts in Phase 1b will be conducted in the United States only.  Phase 1b 
monotherapy will be conducted globally.  
This study includes a Phase 1a FPA150 Monotherapy Dose Escalation, Phase 1a Monotherapy 
Dose Exploration, Phase 1a combination Safety Lead-in (FPA150 + pembrolizumab), a 
Phase 1b FPA150 Monotherapy Dose Expansion, and a Phase 1b combination Dose 
Expansion (FPA150 + pembrolizumab).  
The Phase 1a Monotherapy Dose Escalation will include an initial accelerated titration design 
followed by a standard 3+3 dose escalation design until the MTD and/or RD for Phase 1b is 
determined.  The Phase 1a combination Safety Lead-In will start enrolling once the FPA150 
monotherapy RD is identified in Phase 1a monotherapy dose escalation and will continue until 
the FPA150 MTD/RD in combination is identified. 
Phase 1a FPA150 monotherapy Dose Exploration may include cohorts that may enroll beyond 
3 patients whose tumors express high levels of B7-H4 protein and/or have varying levels of 
B7H4 expression
 
 to further evaluate safety, PK, 
pharmacodynamics, and clinical activity at that dose (to be conditional upon the dose level 
clearing DLT criteria).. 
Phase 1b will be the Dose Expansion (monotherapy and combination) portion of the study. 
Enrollment into Phase 1b Dose Expansion will begin after identification of the MTD and/or 
RD in Phase 1a (monotherapy and Safety Lead-in). Preliminary efficacy will be evaluated in 
Phase 1b in planned expansion cohorts that include patients with specific tumor types that are 
B7-H4+ advanced solid tumors.  

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Archival tumor tissue or fresh biopsy requirements are as follows: 
Required for all patients in Phase 1a Monotherapy Dose Escalation: 
• 
Provision of  archival tumor tissue (or fresh biopsy if archival tissue is not available) for 
retrospective biomarker analysis for all patients 
Required for all patients in Phase 1a Combination Safety Lead-in: 
• 
Pre-screening of archival tumor tissue (or fresh biopsy required if archival tissue is not 
available) to evaluate for B7-H4 expression levels through IHC testing performed at a 
central laboratory and for retrospective biomarker analysis. 
Required for all patients in Phase 1a Monotherapy Dose Exploration: 
• 
Pre-screening test for B7-H4 expression levels through IHC testing and retrospective 
biomarker analysis will be performed at a central laboratory; fresh biopsy tissue will be 
required for this test if archival tissue is not available. 
• 
Fresh biopsies mandatory during screening and on-treatment (prior to C3D1, please refer 
to Appendix 2 for additional information). 
Required for all patients in Phase 1b Monotherapy and Combinbination Dose 
Expansion: 
• 
Pre-screening of archival tumor tissue to evaluate for B7-H4 expresion level through 
IHC testing and retrospective biomarker analysis will be performed at a central 
laboratory; fresh biopsy tissue will be required for this test if archival tissue is not 
available. 
• 
Fresh biopsies mandatory for a subset of patients (at least 15 patients per 30-patient 
cohort) during screening and on-treatment (prior to C3D1), for expanded 
pharmacodynamic analysis 

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Figure 3: 
Study Schema- Monotherapy 
 
 
Figure 4: 
Study Schema - Combination 
 

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Cohort Review Committee 
Safety will be monitored throughout the study by the Sponsor’s Cohort Review Committee 
(CRC), consisting of at least the Sponsor’s Medical Monitor, Safety Representative, and 
Study Investigators participating in Phase 1a. The CRC will meet routinely to review the 
emerging safety, PK, pharmacodynamics, and efficacy data, and to make dose escalation 
decisions. The CRC may recommend further evaluation of the safety at a given dose. The 
CRC will also review cumulative safety data in order to identify safety concerns that may 
emerge due to cumulative exposure beyond the DLT window. The process for dose escalation 
decisions and dose interval recommendations and the roles and responsibilities of the CRC 
will be detailed in the CRC Charter. 
 
Study Design: Phase 1a Dose Escalation 
Cohorts are planned at doses from 0.01 to 20 mg/kg, and enrollment will depend on safety and 
tolerability. Phase 1a Monotherapy Dose Escalation of the study will include an initial 
accelerated titration design followed by a standard 3+3 dose escalation design at dose levels 
≥ 1 mg/kg until the MTD and/or RD for Phase 1b is determined.  As of 28 January 2019, the 
RD for FPA150 monotherapy has been established as 20 mg/kg Q3W. 
The proposed dosing cohorts are outlined in Table 3. 
Table 3:  
Proposed Dose Levels for Phase 1a FPA150 Monotherapy 
Dose Level 
Cohort 
Dose 
Regimen 
-1 
- 
FPA150 0.005 mg/kg 
Q3W 
1 
1aM1 
FPA150 0.01 mg/kg 
Q3W 
2 
1aM2 
FPA150 0.03 mg/kg 
Q3W 
3 
1aM3 
FPA150 0.1 mg/kg 
Q3W 
4 
1aM4 
FPA150 0.3 mg/kg 
Q3W 
5 
1aM5 
FPA150 1 mg/kg 
Q3W 
6 
1aM6 
FPA150 3 mg/kg 
Q3W 
7 
1aM7 
FPA150 10 mg/kg 
Q3W 
8 
1aM8 
FPA150 20 mg/kg 
Q3W 
Abbreviations: Q3W = once every 3 weeks.  
 
4.1.2.1 
Phase 1a Combination Safety Lead-in (Ovarian B7-H4+ Patients Only)  
Once the MTD and/or RD of FPA150 monotherapy in Phase 1a Dose Escalation is identified, 
the Sponsor will open a Safety Lead-in for the combination of FPA150 and pembrolizumab.  
At least 3 patients will be enrolled at the monotherapy RD of FPA150 in combination with 
pembrolizumab 200 mg IV Q3W and evaluated for DLTs by the CRC.  If required due to the 
presence of DLTs, the dose of FPA150 will be reduced in accordance with the algorithm for 

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de-escalation described in Table 4.  The same dose levels that were assessed during dose 
escalation for FPA150 monotherapy will be evaluated for the combination in reverse order 
(from highest to lowest).  Once the RD for the combination of FPA150 and pembrolizumab is 
identified the Sponsor may treat additional patients at that dose for additional safety 
assessment (up to 10 patients total).   
Table 4: 
Proposed Dose Cohort/Levels for Phase 1a Combination Safety Lead-in 
(FPA150 in Combination with Pembrolizumab) 
Cohort 
Dose 
Regimen 
1aC1 
FPA150 (RD) + pembrolizumab 200 mg IV  
Q3W 
1aC2 
FPA150 (dose level -1) + pembrolizumab 200 mg IV 
Q3W 
1aC3 
FPA150 (dose level -2) + pembrolizumab 200 mg IV 
Q3W 
Abbreviations: IV = intravenous; Q3W = once every 3 weeks; RD = recommended dose. 
 
4.1.2.2 
Definition of a Dose-Limiting Toxicity 
4.1.2.2.1 
FPA150 Monotherapy  
DLTs during Phase 1a Dose Escalation are defined as any of the following events regardless 
of attribution (except for those events clearly due to the underlying disease or extraneous 
causes): 
• Any Grade 3 or higher non-hematologic toxicity (except Grade 3 nausea, vomiting and 
diarrhea) occurring with the first 21 days of treatment 
• Grade 3 nausea, vomiting, diarrhea lasting > 72 hours, despite optimal supportive care, 
occurring within first 21 days of treatment 
• 
Febrile neutropenia and/or documented infection with absolute neutrophil count (ANC) 
< 1.0 × 109 per L, Grade 4 neutropenia lasting more than 7 days, Grade 4 
thrombocytopenia (< 25.0 × 109 per L), or Grade 3 thrombocytopenia (< 50.0–25.0 × 
109 per L) accompanied by bleeding within first 21 days of treatment 
• 
Aspartate aminotransferase/alanine transaminase (AST/ALT) > 3 × upper limit of normal 
(ULN) and concurrent total bilirubin > 2 × ULN not related to liver involvement with 
cancer 
• 
Other Grade 3 laboratory values that are not of clinical significance according to 
Investigator and Sponsor agreement that do not resolve within 72 hours 
• 
Any Grade 4 laboratory value regardless of clinical sequelae 

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4.1.2.2.2 
FPA150 Combined with Pembrolizumab (Safety Lead-in)  
Additional DLT Considerations for the Combination of FPA150 and Pembrolizumab  
Because pembrolizumab is a known immune checkpoint inhibitor and one of the proposed 
mechanisms of action of FPA150 is immune checkpoint blockade, immune-related adverse 
events (irAEs) are anticipated with this combination. An irAE is defined as a clinically 
significant AE that is associated with study drug exposure, of unknown etiology, and is 
consistent with an immune-mediated mechanism. Based on that background, the first 
occurrence of the following irAEs will not be considered a DLT because they are expected 
with immune therapy:  
• Grade 3 tumor flare (defined as local pain, irritation, or rash localized at sites of known or 
suspected tumor) 
• Grade 3 rash 
• Grade 3 immune-related adverse event (irAE) that resolved to a Grade 1 or less within 
14 days 
• Transient (resolving within 6 hours of onset) Grade 3 infusion-related AE 
A second occurrence of these events (except Grade 3 tumor flare) either in the same or 
different patient during the DLT period will be considered a DLT 
4.1.2.3 
Dose-Limiting Toxicity Evaluation and Dose Escalation (FPA150 
Monotherapy and Combination Safety Lead-in) 
The DLT evaluation interval begins on the first day of treatment upon start of infusion and 
continues for 21 days. In Phase 1a Dose Escalation, patients’ second dose must be at least 
21 days after the first dose.  
Review of safety, PK and pharmacodynamic profiles may inform decisions to add cohorts 
with alternative dose levels or dose regimens (eg, different dosing frequency, higher dose 
levels) in order to reach an optimal target exposure. 
All dose escalation decisions will be based on the assessment of DLTs and overall safety and 
tolerability, and will be made after the last patient enrolled in each cohort has completed the 
first treatment cycle (ie, 21 days). Dose escalation decisions will be agreed upon by the CRC 
as outlined in Section 4.1.1. 
Patients who receive at least one dose of study drug during the 21-day evaluation interval, or 
patients who discontinue study treatment for drug-related AEs before the DLT evaluation 
interval is complete, will be considered evaluable for DLT determination. Patients who 
discontinue study treatment for reasons other than drug-related AEs before the DLT 
evaluation interval is complete may be replaced. In consultation with Investigators, the 
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For monotherapy dose escalation an accelerated titration design enrolling at least 1 patient at 
each dose level is planned for dose levels 0.01, 0.03, 0.1, and 0.3 mg/kg. Dose escalation to 
the next dose level may proceed after at least 1 patient completes the 21-day evaluation 
interval. If a single patient experiences a DLT or at least 2 patients experience moderate AEs 
(at any dose level) during the 21-day evaluation interval, additional patients will be enrolled at 
the current dose level and standard 3+3 dose escalation criteria will apply for that cohort as 
well as all subsequent dosing cohorts. Moderate AEs are defined as ≥ Grade 2 AEs regardless 
of attribution (except for those events clearly due to the underlying disease or extraneous 
causes). Grade 2 laboratory values will not be considered as moderate AEs for this purpose 
unless accompanied by clinical sequelae.  
The algorithm outlined in Table 5 will be used for all standard 3+3 dose escalation decisions 
in Phase 1a monotherapy. If not already applied at a lower dose level for the reasons stated 
above, escalation for dose levels ≥ 1 mg/kg will follow standard 3+3 dose escalation criteria. 
Table 5:  
Phase 1a Algorithm for FPA150 Monotherapy Dose-Escalation Decisions 
Number of Patients with DLT 
at a Given Dose Level 
Dose Escalation Decision Rule 
0/3 
Enroll 3 patients at next dose level (next/higher cohort) 
1/3 
Enroll 3 additional patients at current dose level (current cohort) 
≥ 2/3 
Stop enrollment. Enter 3 more patients at the previous dose level 
(previous/lower cohort), if only 3 were previously entered, or at an 
intermediate dose level 
1/6 
Enroll 3 patients at next dose level (next/higher cohort) 
≥ 2/6 
Stop enrollment. Enter 3 more patients at the lower dose level 
(previous/lower cohort), if only 3 were previously entered, or at an 
intermediate dose level 
Abbreviations: DLT = dose-limiting toxicity. 
The algorithm outlined in Table 6 will apply for dosing decisions for the FPA150 and 
pembrolizumab combination. 

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Table 6: 
Algorithm for Dose De-Escalation Decisions for FPA150 Safety Lead-In in 
Combination with Pembrolizumab in Phase 1a 
Number of Patients with 
DLT at a Given Dose Level 
Dosing Decision Rule 
0/3 
Proceed with enrolment of up to 10 total patients at that dose level for 
additional safety assessment 
1/3 
Enrol 3 additional patients at current dose level (current cohort) 
≥ 2/3 
Stop enrolment at current cohort and de-escalate FPA150 to one dose level 
below current dose  
1/6 
Proceed with enrolment of up to 10 total patients at that dose level 
≥ 2/6 
Stop enrolment at current cohort and de-escalate FPA150 to one dose level 
below current dose.  
 
4.1.2.4 
Determination of the Recommended Dose or Maximum Tolerated Dose  
The MTD and/or RD of FPA150 monotherapy and FPA150 combined with pembrolizumab 
for Phase 1a will be identified based on an evaluation of the overall safety, tolerability, 
pharmacodynamics, PK, and preliminary efficacy. The RD will take into account toxicities 
observed both during and beyond the DLT evaluation period as well as dose reductions and 
discontinuations due to toxicity that do not meet the DLT criteria. The RD, therefore, may or 
may not be the same as the identified MTD. For example, if the MTD is not reached, or if data 
from subsequent cycles of treatment from Phase 1a provide additional insight on the safety 
profile, then the RD may be a different, though not higher, dose than the MTD.  
The MTD will be at a dose level where ≤ 1/3-6 patients reported a DLT. The RD will be a 
dose where ≤ 1/6 patients reported a DLT, but may be lower than the MTD.  
In the event that no MTD is identified and drug exposure exceeds what is deemed necessary 
based on nonclinical pharmacology data or the clinical PK and pharmacodynamic data 
(if available), the Sponsor and the Investigators may make a decision to discontinue dose 
escalation. 
 
Study Design: Phase 1a Dose Exploration 
Phase 1a includes a dose exploration cohort that may enroll beyond 3 patients (up to 
20 additional patients across all dose levels).  This 20 patients include 10 patients whose 
tumors express high levels of B7-H4 protein (3 mg and 10 mg), to further 
evaluate safety, PK, pharmacodynamics, and clinical activity at that dose (to be conditional 
upon the dose level clearing DLT criteria) of FPA150 monotherapy.  It also includes up to 10 
patients selected to have varying levels of B7-H4 expression 
 
 dosed at the FPA150 monotherapy MTD/RD. 

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Table 7: 
Proposed Dose Cohort/Level for Phase 1a Dose Exploration 
Cohort 
Dose/Regimen 
B7-H4 Status 
1aE1 
FPA150 3 mg/kg 
High 
1aE2 
FPA150 10mg/kg 
High 
1aE3 
FPA150 monotherapy MTD/RD 
 
Abbreviations: MTD = maximum tolerated dose; Q3W = once every 3 weeks; RD = recommended dose 
Toxicities observed in these patients will contribute to the overall assessment of safety and 
tolerability, but will not be included in the formal DLT calculations per Protocol Table 5. 
 
Study Design: Phase 1b Dose Expansion 
Enrollment in Phase 1b monotherapy and in combination with pembrolizumab will begin 
when the MTD and/or RD has been identified by the CRC (refer to Section 4.1.1), based on 
overall safety, tolerability, objective response, PK, pharmacodynamics from the Phase 1a part 
of the study. 
Phase 1b will consist of tumor-specific cohorts of up to 30 patients each.  
Requirements for archival tumor tissue and fresh biopsies by study phase are listed in 
Section 4.1. Separate ICFs for patients will be required regarding provision of fresh biopsies. 
During the Screening Period, the patient will undergo protocol-specified screening procedures 
to ensure all eligibility criteria are met. Enrollment in Phase 1b will initially occur in 
3 monotherapy cohorts and one cohort with FPA150 in combination with pembrolizumab 
(once the Safety Lead-in is completed and the MTD/RD for the combination is identified) as 
outlined in Table 8.  
Table 8:  
Phase 1b Expansion Cohorts and Tumor Types  
Cohort 
Tumor Type 
Therapy Type (Monotherapy or Combination) 
1b1 
Breast cancer 
Monotherapy: FPA150 
1b2 
Ovarian cancer 
Monotherapy: FPA150 
1b3 
Endometrial cancer 
Monotherapy: FPA150 
1bC1 
Ovarian cancer 
Combination: FPA150 with pembrolizumab 

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Number of Patients 
The total number of patients planned for this study is estimated to be approximately 278.  
Phase 1a will enroll approximately 68 patients depending on incidence of DLTs; this number 
of 68 patients includes: 
• Up to 23 to 26 patients in the Phase 1a Dose Escalation and  
• Up to 6 to 22 patients in the FPA150 and pembrolizumab combination Safety Lead-in and 
• Allows for up to 20 additional patients in 2 cohorts in Phase 1a Dose Exploration. 
Phase 1b will enroll up to 210 patients with specific tumor types with B7-H4 expression levels 
determined by IHC; this number of 210 patients includes:  
• Up to 30 patients planned for each of three monotherapy expansion cohorts (refer to 
Table 8) and one FPA150 in combination with pembrolizumab cohort. 
• Additional tumor type-specific cohorts may be enrolled based on emerging data.  
No individual expansion cohort will exceed 30 patients. 
 
Patient and Study Completion 
The duration of study for an individual patient includes screening (up to 28 days), treatment 
and an End of Treatment (EOT) follow-up period which will include visits at approximately 
28 (±7) days and 100 (±7) days after the last dose. Since all patients are eligible to be treated 
until disease progression, the actual treatment duration for each individual patient will vary 
depending on the anticipated time to progression for their respective tumor type. Treatment 
beyond disease progression may be allowed in patients with initial Response Evaluation 
Criteria in Solid Tumors version 1.1 (RECIST v1.1) defined progressive disease if the 
benefit/risk assessment favors continued administration of study treatment (eg, patients are 
continuing to experience clinical benefit as assessed by the Investigator, and tolerating 
treatment). 
In addition, patients enrolled in Phase 1b Dose Expansion will be followed for survival 
(including scans and survival status every 12 weeks [Q12W]) for up to 2 years). 
 
End of Study Definition 
The study will end when the last patient enrolled completes the EOT follow-up period. 
The EOT follow-up period will include visits at approximately 28 (±7) days and 100 (±7) 
days after the last dose.  

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Scientific Rationale for Study Design 
This is a Phase 1a/1b study. Phase 1a includes an accelerated titration design followed by 
standard 3+3 dose escalation design in unselected solid tumor patients.  Once MTD/RD of 
FPA150 monotherapy is identified a cohort of patients will be enrolled on a Phase 1a Safety 
Lead-in with FPA150 + pembrolizumab to determine the RD of FPA150 in the combination. 
Phase 1a will also include the option of enrolling up to 20 additional patients at 1 or more 
dose levels with varying levels of B7-H4 expression. Fresh biopsies will be mandatory in 
these additional patients. This will enable a more robust exploration of safety, PK and 
pharmacodynamics at any dose level.  
Phase 1b is a dose expansion portion in patients with advanced breast, ovarian, and 
endometrial cancer that will be selected based on B7-H4 expression. These tumor types have 
been identified based on their known high prevalence of B7-H4 expression (Section 2.1) and 
limited availability of effective therapies in the unresectable and metastatic setting.  Based on 
the preclinical activity of FPA150 and PD-L1 inhibitors (see Section 2.2.2.2) Phase 1b will 
also include a cohort of the combination of FPA150 and pembrolizumab to evaluate safety, 
tolerability and preliminary efficacy. The initial tumor type to be evaluated with the 
combination will be ovarian cancer based on the high unmet need in this population, high 
expression of B7-H4 and the limited clinical benefit observed with anti-PD1 agents alone.  
Additional cohorts with different tumor types or combinations may be enrolled based on 
emerging clinical and translational data for this pathway and molecule. Phase 1b Dose 
Expansion will enable a more thorough investigation of the clinical and biological activity of 
FPA150 monotherapy and in combination with pembrolizumab in more homogenous patient 
groups (by tumor type and biomarker expression) and will help define further clinical 
development of this molecule.  
Fresh pre-treatment and on treatment study biopsies are mandatory in at least 15 of 30 patients 
enrolled in each Phase 1b cohort which may provide insight into the mechanism of action of 
FPA150 and help further refine potential tumor tissue-based biomarkers The primary 
endpoints for both the Phase 1a and Phase 1b portions are related to safety and tolerability and 
the statistical analyses will be descriptive. Additional details regarding the statistical 
assumptions for secondary endpoints related to evaluating preliminary efficacy in the 
30-patient expansion cohort are described in Section 9.1.  
 
Justification for Dose and Dosing Regimen 
FPA150 is a glycoengineered IgG1 anti-B7-H4 monoclonal antibody with enhanced ADCC 
and checkpoint blockade activities, developed to be administered to patients with advanced 
solid tumors. The International Conference on Harmonization (ICH) S9 guidance 
(“Nonclinical Evaluation for Anticancer Pharmaceuticals”) is applied to select FPA150 
starting dose in human. The proposed starting dose in this study is 0.01 mg/kg IV Q3W. This 
was calculated using the established dose selection guidelines for the MABEL approach 

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(Saber 2016). The design is an accelerated titration followed by standard 3+3 dose escalation 
with approximately half log dose escalations. 
FPA150 will be administered via IV infusion Q3W, which is consistent with a schedule 
commonly used for humanized monoclonal antibodies with an expected half-life of 
approximately 10 to 20 days. The dose of FPA150 will be based on body weight at Cycle 1 
Day 1. After Cycle 1, the FPA150 dose will be recalculated at each infusion visit only if the 
patient’s weight has changed > 10% from Cycle 1, Day 1. 
The proposed dose of pembrolizumab of 200 mg Q3W is consistent with the current approved 
US Prescribing Information. The initial starting dose of FPA150 in combination with 
pembrolizumab will be the RD identified during monotherapy dose escalation. This is an 
acceptable approach given the preliminary safety data of FPA150 monotherapy and the well 
characterized safety profile of pembrolizumab.  Step down dosing of FPA150 in response to 
emerging safety data is planned.    
 
Patient Selection 
FPA150 is an antibody designed to recognize B7-H4 which is expressed highly on tumors, 
such as on breast cancer, ovarian cancer, and endometrial cancer. Because it is predicted that 
patients whose tumors have higher expression of the target B7-H4 protein are more likely to 
respond to FPA150, patients will undergo pre-screening to allow selection based on B7-H4 
expression in the Phase 1a Combination Safety Lead-in, Phase 1a Monotherapy Dose 
Exploration and in Phase 1b Dose Expansion (Monotherapy and in combination with 
pembrolizumab).  
Tumor samples (fresh or archival) from all patients will be assessed by IHC to determine the 
expression of B7-H4 protein, and patients in Phase 1b and a subset of patients in Phase 1a will 
be selected based on being positive for B7-H4. 
 
 

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5 
Study Population 
 
Inclusion Criteria 
 
Phase 1a Inclusion Criteria (Monotherapy and Combination Therapy) 
Patients enrolling into Phase 1a must meet all of the following inclusion criteria: 
1) Histologically confirmed solid tumors except primary central nervous system (CNS) 
tumors. 
2) Disease that is unresectable, locally advanced, or metastatic. 
3) Able to understand and sign an IRB/IEC)approved ICF prior to any study-specific 
evaluation. 
4) Patients should be refractory to or intolerant of existing therapy(ies) known to provide 
clinical benefit for their condition. 
5) All patients must have at least one measurable lesion at baseline according to 
RECIST v1.1; tumor sites situated in a previously irradiated area, or in an area subjected 
to other loco-reginal therapy, are not considered measurable unless there has been 
demonstrated progression in the lesion. 
6) Adequate washout for prior anti-cancer therapy (ie, ≥ 5 half-lives or 4 weeks since the 
last dose, whichever is shorter). 
7) Availability of archival tumor tissue for retrospective biomarker analysis, or patient must 
undergo a fresh tumor biopsy during screening if archival tissue is not available (a biopsy 
is required for patients in the Phase 1a Dose Exploration portion).  Archival tissue for 
patients enrolled in Cohort 1b1 (Breast Cancer) must be within 24 months prior to pre-
screening. 
8) Age ≥ 18 years at the time the ICF is signed. 
9) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 
10) Life expectancy of at least 3 months in the opinion of the Investigator. 
11) Willing and able to comply with all study procedures. 
12) Prior radiotherapy must be completed at least 2 weeks before the first dose of study drug. 
13) Prior radiopharmaceuticals (eg, strontium, samarium) must be completed at least 8 weeks 
before the first dose of study drug.  
14) Prior surgery that requires general anesthesia must be completed at least one week before 
first dose of study drug administration. Surgery requiring local/ epidural anesthesia must 
be completed at least 72 hours before first dose of study drug administration. Patients 
must have recovered from any surgery. 

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15) Screening laboratory values must meet the following criteria: 
Hematologic: 
a. 
Neutrophils ≥ 1200 cells/µL 
b. 
Platelets ≥ 75 × 103/µL 
c. 
Hemoglobin (Hb) ≥ 9.0 g/dL 
Renal: 
d. 
Serum creatinine < 1.5 × ULN or creatinine clearance (CrCl) of ≥ 40 mL/minute 
(using Cockcroft/Gault Formula) 
Female CrCl 
= 
(140 – age in years) × (weight in kg) × 0.85 
72 × (serum creatinine in mg/dL) 
 
Male CrCl 
= 
(140 – age in years) × (weight in kg) 
72 × (serum creatinine in mg/dL) 
Hepatic: 
e. 
AST and ALT ≤ 3× ULN (AST and ALT <5× ULN in patients with liver metastases 
is permitted) 
f. 
Bilirubin < 1.5× ULN (except patients with Gilbert's syndrome, who must have total 
bilirubin < 3 mg/dL) 
16) Negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test ≤ 96 hours 
prior to treatment on Cycle 1, Day 1 (women of childbearing potential only). 
17) In sexually active patients (women of child bearing potential and males), willingness to 
use 2 effective methods of contraception, of which 1 must be a physical barrier method 
(condom, diaphragm, or cervical/vault cap) until 6 months after the last dose of FPA150. 
Other effective forms of contraception include: 
• Permanent sterilization (hysterectomy and/or bilateral oophorectomy, or bilateral 
tubal ligation with surgery, or vasectomy) at least 6 months prior to Screening 
• Women of childbearing potential who are on stable oral contraceptive therapy or 
intrauterine or implant device for at least 90 days prior to the study, or abstain from 
sexual intercourse as a way of living 
50)  For Phase 1a Combination Safety Lead-in Patients ONLY:  
50.01 B7-H4 positive ovarian cancer 

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50.02 Histologically or cytologically confirmed  diagnosis of recurrent epithelial 
ovarian, primary peritoneal, or fallopian tube carcinoma  that is refractory to 
existing therapy(ies) known to provide clinical benefit 
50.03)  Progressive disease on or after  at least two prior regimens of treatment 
including at least one platinum-containing regimen, or unable to tolerate 
additional chemotherapy 
50.04)  No prior therapy with an anti-PD1 or PD-L1-directed agent   
 
Phase 1b Inclusion Criteria (Monotherapy and Combination Therapy) 
Patients enrolling into Phase 1b must meet all of the following inclusion criteria: 
18) All Inclusion Criteria for Phase 1a (Exception: Phase 1a Inclusion Criterion #1). 
19) Positive for B7-H4 expression in an archival or fresh tumor sample as evaluated by an 
accompanying validated central laboratory IHC assay.  Archival tissue for patients 
enrolled in Cohort 1b1 (Breast Cancer) must be within 24 months prior to pre-screening. 
20) History of other malignancy is permitted provided it has been definitively treated with no 
evidence of recurrence within the past 2 years (Exception: Definitively treated 
non-melanoma skin cancer, lobular cancer in situ, and cervical cancer in situ within 
2 years are permitted). 
 
Additional Cohort-Specific Inclusion Criteria for Phase 1b (Monotherapy and 
Combination Therapy) 
Cohort 1b1 Breast Cancer  
Triple Negative Breast Cancer (TNBC) 
21.01) Histologically or cytologically confirmed metastatic TNBC  
21.02) At leat two prior lines of systemic chemotherapy with at least one being administered 
in the metastatic setting  
HR+ Breast Cancer  
21.03) Histologically or cytologically confirmed metastatic HR+ breast carcinoma 
21.04) Patients must have received at least two prior lines of hormonal therapy 
21.05) Patients must have received at least one prior line of systemic chemotherapy (in the 
adjuvant or metastatic setting) 
Cohort 1b2 Ovarian Cancer 
22.01) Histologically or cytologically confirmed diagnosis of recurrent epithelial ovarian, 
primary peritoneal, or fallopian tube carcinoma that is refractory to existing 
therapy(ies) known to provide clinical benefit 

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22.02) Progressive disease on or after at least two prior regimens of treatment including at 
least one platinum-containing regimen, or unable to tolerate additional chemotherapy 
Cohort 1b3 Endometrial Cancer 
23.01) Histologically or cytologically confirmed recurrent or persistent endometrial cancer 
that is refractory to curative or established treatments 
23.02) Progressive disease on or after at least one prior regimen of systemic chemotherapy, 
or unable to tolerate systemic chemotherapy 
Cohort 1bC1 Ovarian Cancer 
24.01) Histologically or cytologically confirmed diagnosis of recurrent epithelial ovarian, 
primary peritoneal, or fallopian tube carcinoma  that is refractory to existing 
therapy(ies) known to provide clinical benefit 
24.02) Progressive disease on or after at least two prior regimens of treatment including at 
least one platinum-containing regimen, or  unable to tolerate additional chemotherapy  
24.03) No prior therapy with an anti-PD1 or PD-L1-directed agent 
No waivers will be granted for any of these inclusion criteria. 
 
Eligibility Criteria 
Exclusion Criteria (Phase 1a And Phase 1b)  
Patients who meet ANY of the following criteria will be excluded from study entry: 
1) Immunosuppressive doses of systemic medications, such as steroids or absorbed topical 
steroids (doses > 10 mg/day prednisone or equivalent daily) must be discontinued at least 
two weeks before the first dose of study drug. Short courses of high dose steroids, 
continuous low dose (prednisone < 10 mg/day), inhaled, intranasal, intraocular, and joint 
injections of steroids are allowed 
2) Decreased cardiac function with New York Heart Association (NYHA) > Class 2 
at screening 
3) Uncontrolled or significant heart disorder such as unstable angina 
4) QT interval corrected for heart rate (QTc) per institutional guidelines> 450 msec 
for males or > 470 msec for females at screening 
5) History of  ADAs, , severe allergic, anaphylactic, or other infusion-related reaction to a 
previous biologic agent  
6) Known hypersensitivity to any component of the investigational product (IP) formulation 
including active ingredient, sodium acetate, sucrose, and polysorbate 20 (refer to 
Section 6.1.1) 

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7) Vaccines (eg, human papilloma virus [HPV] vaccine) within 4 weeks before the first dose 
of study drug. The inactivated seasonal influenza vaccine can be given to patients before 
treatment and while on therapy without restriction. Influenza vaccines containing live 
virus or other clinically indicated vaccinations for infectious diseases (ie, pneumovax, 
varicella, etc.) may be permitted, but must be discussed with the Sponsor’s Medical 
Monitor and may require a study drug washout period prior to and after administration of 
the vaccine. 
8) Current unresolved infection or history of chronic, active, clinically significant infection 
(viral, bacterial, fungal, or other) which, in the opinion of the Investigator, would 
preclude the patient from exposure to a biologic agent or may pose a risk to patient 
safety. 
9) Patients with abnormal serum chemistry values that in the opinion of the Investigator are 
considered to be clinically significant. This includes patients who show clinical signs and 
symptoms related to their abnormal serum chemistry values, as well as patients whose 
serum chemistry values are asymptomatic, but clinically significant according to the 
Investigator (eg, hypokalemia or hyponatremia). 
10) Any uncontrolled medical condition or psychiatric disorder which, in the opinion of the 
Investigator, would pose a risk to patient safety or interfere with study participation or 
interpretation of individual patient results 
11) Pregnant or breastfeeding 
12) Active, known, or suspected autoimmune disease. Patients with Type I diabetes mellitus, 
hypothyroidism requiring only hormone replacement, skin disorders (such as vitiligo, 
psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to 
recur in the absence of an external trigger, are permitted to enroll. 
13) Known history of testing positive for human immunodeficiency virus (HIV) 1 or 2 or 
known acquired immunodeficiency syndrome (AIDS). 
14) Positive test for hepatitis B virus surface antigen (HBsAg) or detectable hepatitis C virus 
ribonucleic acid (HCV RNA) indicating acute or chronic infection. 
15) Ongoing adverse effects from prior treatment > Grade 1 (with the exception of Grade 2 
alopecia or peripheral neuropathy) based on National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE). 
16) Symptomatic interstitial lung disease or inflammatory pneumonitis. 
17) Untreated or active CNS or leptomeningeal metastases. Patients are eligible if metastases 
have been treated and patients are neurologically returned to baseline or neurologically 
stable (except for residual signs or symptoms related to the CNS treatment) for at least 
2 weeks before the first dose of study drug. 
18) Evidence of coagulopathy or bleeding diathesis. Patients receiving stable therapeutic 
doses of anti-coagulants will be permitted. 

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19) Transfusion of blood or platelets completed within 72 hours before the first dose of study 
drug. 
20) Any uncontrolled inflammatory GI disease including Crohn’s Disease and ulcerative 
colitis 
21) For Cohort 1b1 only: Patients with HER2 positive disease 
No waivers will be granted for any of these exclusion criteria. 
 
Lifestyle Restrictions 
There is not enough information currently available to make any specific recommendations 
regarding lifestyle restrictions.  
 
Screen Failures 
Patients in the Phase 1a Dose Exploration and in Phase 1b Dose Expansion who test negative 
for B7-H4 will be considered Pre-Screen-Failures. Patients who test positive and enter the 
Screening Period, but do not enroll, will be considered Screen-Failed. 
 
 

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6 
Treatments 
 
Treatments Administered 
 
FPA150 Identity 
FPA150 drug product is supplied for IV administration as a sterile, aqueous, colorless to 
slightly yellowish, pyrogen-free solution supplied in single-use glass vials. The composition 
of the drug product contains 20 mg/mL active ingredient, 20 mM sodium acetate, 270 mM 
sucrose, 0.05% (w/v) polysorbate 20 at pH 5.0. The container-closure system consists of a 
5 mL Type I glass vial, sealed with a bromobutyl rubber stopper, and a flip-off cap. The final 
drug product will be provided as 2° to 8°C refrigerated liquid protected from light which is 
diluted for administration according to instructions provided in a separate Pharmacy Manual. 
A 20 mL vial will be available in the second half of 2019.  The composition of the drug 
product contains 20 mg/mL active ingredient, 20 mM sodium acetate, 270 mM sucrose, 
0.05% (w/v) polysorbate 20 at pH 5.0. The container-closure system consists of a 20 mL 
Type I glass vial, sealed with a bromobutyl rubber stopper, and a flip-off cap. 
FPA150 will be supplied in a sterile vial for dilution into an IV bag for administration by the 
study center. 
 
Pembrolizumab 
Pembrolizumab for injection is a sterile, preservative-free, clear to slightly opalescent, 
colorless to slightly yellow solution that requires dilution for intravenous infusion. Each vial 
contains 100 mg of pembrolizumab in 4 mL solution. Each 1 mL solution contains 25 mg of 
pembrolizumab and is formulated in: L-histidine (1.55 mg), polysorbate 80 (0.2 mg), sucrose 
(70 mg) and Water for Injection. For additional information, refer to the Keytruda® 
(pembrolizumab) Prescribing Information (Keytruda® USPI).  FPA150 + pembrolizumab 
combination cohorts will only enroll in the United States. 
Pembrolizumab is available for injection as a 50 mg lyophilized powder in single-use vial for 
reconstition and in 100 mg/4 mL (25 mg/mL) solution in single use vial.   
The lyophilized powder is reconstituted by adding 2.3 mL of Sterile Water for Injection, USP 
by injecting the water along the walls of the vial and not directly on the lyophilized powder 
(resulting concentration 25 mg/mL).  Slowly swirl the vial and allow up to 5 minoutes for the 
bubbles to cear.  Do not shake the vial.  
The injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly 
yellow solution that requires dilution for intravenous infusion. . Each 1 mL of solution 
contains 25 mg of pembrolizumab and is formulated in: L-histidine (1.55 mg), polysorbate 80 
(0.2 mg), sucrose (70 mg) and water for Injection.  Please refer to pembrolizumab USPI  

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Treatment Packaging, Labeling, and Storage 
 
FPA150 
FPA150 will be packaged and labeled as a 5 mL or 20 mL (to be available in second half of 
2019) fill in ISO 6R vials by the Sponsor (or designee) per applicable local regulatory 
requirements.  
All FPA150 vials must be stored refrigerated at 2° to 8°C in accordance with the 
manufacturer’s instructions as provided in the Pharmacy Manual. Until dispensed to patients, 
FPA150 will be stored in a securely locked area, accessible to authorized personnel only. 
 
Pembrolizumab 
For the combination cohorts pembrolizumab’s .   
packaging, labelling, and storage of pembrolizumab should be in accordance with the 
Keytruda® USPI , the Pharmacy Manual, and relevant local guidelines.    
 
Administration and Preparation 
 
FPA150  
FPA150 will be administered as a 60-minute IV infusion Q3W in 21-day cycles until 
progressive disease or unacceptable toxicity. Proposed dose levels to be studied are outlined in 
Table 3 for Phase 1a Dose Escalation. Please refer to the pharmacy manual for any additional 
dosing instructions for dose levels below 1 mg/kg.  
The dose of FPA150 will be based on body weight at Cycle 1 Day 1. After Cycle 1, the 
FPA150 dose will be recalculated at each infusion visit only if the patient’s weight has 
changed > 10% from Cycle 1, Day 1. 
Further instructions on drug preparation and administration are in the Pharmacy Manual. 
There is no pre-specified maximum number of doses of FPA150 monotherapy. Patients may 
continue receiving FPA150 according to their study specified cohort/ dose until Investigator-
assessed clinical progression, unacceptable toxicity, or until the patient meets any of the other 
protocol-specified withdrawal criteria. 
A pharmacist (or other responsible person) will prepare FPA150 for administration. After 
calculating the number of vials based on the patient’s weight, FPA150 will be diluted in a 
0.9% sodium chloride solution or 5% dextrose in water solution. Prepared FPA150 should be 
administered ≤4 hours after preparation under ambient temperature.  

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FPA150 will be administered under medical supervision over approximately 60-minute 
(± 5 minutes) IV infusion via a peripheral vein or central venous catheter. The IV 
administration set for FPA150 infusion must contain a 0.22 µm in-line filter or a 0.22 µm 
syringe filter.  
All patients must be monitored for at least 4 hours after the end of the first infusion of 
FPA150. Patients in whom intrapatient dose escalation is planned (ie, patients enrolled at dose 
levels below 1 mg/kg) should also be monitored for at least 4 hours after the end of infusion at 
each dose escalation. Infusion of FPA150 must be stopped, reduced, interrupted, or 
discontinued according to Section 6.4.4 (Dose Modification Criteria) and Section 6.4.6 
(Dose Interruptions During Study Treatment Administration). If a patient experiences an 
infusion reaction, the patient’s vital signs (temperature, blood pressure, pulse, and respiration 
rate) should be monitored during the infusion as well as every 30 minutes after the infusion 
for a minimum of 2 hours and until resolution of the infusion reaction. 
 
Pembrolizumab 
Pembrolizumab should be prepared according to the Keytruda® USPI.   
Table 9 details the treatment regimen for the combination cohorts.  Pembrolizumab will be 
administered after completion of the FPA150 IV infusion. Pembrolizumab will be 
administered at a dose of 200 mg by IV infusion over 30 minutes (± 5 minutes) starting on 
C1D1 and repeated Q3W on Day 1 of each 21-day cycle after all procedures and assessments 
have been completed. Pembrolizumab should not be co-administered with FPA150. 
Further information regarding dosing and preparation of pembrolizumab can be found in the 
Keytruda® USPI.  
Table 9: 
Study Treatment Regimen of Combined Treatment of FPA150 and 
Pembrolizumab 
Study 
Treatment 
Dosage 
Formulation 
Unit Dose 
 Strengths 
Dosage 
Level (s) 
Route of 
Administration 
Regimen/ 
Treatment 
Period 
FPA150 
Solution for 
infusion 
Single-use glass vials 
(5 mL and 20 mL) 
containing 20 mg/mL 
active ingredient 
Table 4 
60-minute 
(± 5 minutes) IV 
infusion 
Day 1 of each 
cycle (Q3W) 
30 to 60 minutes  
Pembrolizumab 
Solution for 
infusion or 
lyophilized 
powder 
100 mg/vial 
containing 25 mg/mL 
active ingredient or 
50 mg lyophilized 
powder in single use 
vial for reconstitution 
200 mg 
30-minute IV 
infusion 
Day 1 of each 
21-day cycle 
(Q3W) 
After FPA150 
 

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Dose Modifications 
In Phase 1a the starting dose level of FPA150 is 0.01 mg/kg. Subsequent dose escalations 
between cohorts in Phase 1a are described in Section 4.1.1. The dose of FPA150 for Phase 1b 
will be determined by evaluation of the data from Phase 1a of the study, as described in 
Section 4.1.4. 
All patients in the combination cohorts receive pembrolizumab 200 mg IV Q3W.  Dose 
modifications for pembrolizumab are described in the package insert.  Dose reductions for 
pembrolizumab are not permitted.  
 
Dose Modification Based on Weight  
A complete physical examination including height and weight will be performed at screening. 
The dose of FPA150 will be based on body weight at Cycle 1 Day 1. After Cycle 1, the 
FPA150 dose will be recalculated at each infusion visit only if the patient’s weight has 
changed > 10% from Cycle 1, Day 1. 
The dose of pembrolizumab will not be adjusted based on weight. 
 
Dose Escalation within a Cohort 
In Phase 1a, intrapatient dose escalation will be permitted in patients enrolled at dose levels 
below 1 mg/kg provided: 
• The patient did not experience a DLT 
• All other AEs have recovered to Grade 1 or lower prior to dose escalation  
• The patient may only dose escalate by a maximum of 1 dose level every 21 days 
• The patient cannot dose escalate beyond 1mg/kg dose level unless the dose level has been 
cleared according to the standard 3+3 dose escalation design as described in Section 4.1 
• Patients treated at dose levels up to 1 mg/kg may be escalated to a higher dose level if the 
patient has had a radiographic response, subsequently progressed and the higher dose 
levels have cleared DLT. 
Intrapatient dose escalation will only be permitted after a discussion between the sponsor 
medical monitor and treating physician taking into account the overall safety experience, PK 
and PD data available at the time of the request.  
In Phase 1b, patients will be treated at the MTD and/or RD as determined from Phase 1a, and 
dose escalation will not be permitted. 

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Toxicity at Lowest Dose Level 
If the MTD is unexpectedly exceeded at the first dose level of FPA150 (0.01 mg/kg), the dose 
may be reduced to 0.005 mg/kg (refer to Table 3 for an outline of FPA150 dose levels for 
Phase 1a). Decisions on how to next proceed will be based on safety, tolerability, and PK 
data, and will be determined by the CRC (refer to Section 4.1.1). 
 
Dose Modification Criteria for FPA150 
Dose reductions for FPA150 may be permitted for patients on treatment beyond the DLT 
Period and can be assessed using local laboratories. If a patient requires a dose reduction of 
FPA150 during the DLT period, they will be considered to have a DLT and be permanently 
discontinued from FPA150. Dose reductions for FPA150-related AEs should follow the 
guidelines outlined in Table 10.  The treating physician may choose to interrupt or discontinue 
FPA150 at any time outside of these guidelines if they believe it is necessary to ensure patient 
safety. It is recommended that the treating physician disuss the proposed dosing modification 
with the FivePrime medical monitor prior to making the change. Patients may resume 
FPA150 if the event returns to baseline or ≤ Grade 1 in accordance with the guidelines 
outlined in Table 10. Any variations from these guidelines must be discussed with the 
FivePrime Medical Monitor prior to dosing and must take into consideration the overall 
benefit and risks for the patient of continued participation in the study. 
Table 10: 
Dose Modification Guidelines for FPA150 (Non-infusion Toxicity) 
FPA150-related  
Toxicity Grade 
Dose Schedule 
New FPA150 Dose 
Grade 1 or 2 
No delay or missed dose 
required 
100% of dose 
Grade 3  
(first occurrence) 
Delay or miss dose until 
recovery to baseline or 
Grade 1  
If recovery to baseline or Grade 1 within 
28 days, may resume at 100% of starting 
dose or 1 dose lowera  
Grade 3  
(second occurrence) 
Delay or miss dose until 
recovery to baseline or 
Grade 1  
If recovery to baseline or Grade 1 within 
28 days, may resume at 1 level lowera 
than previous dose or discontinue  
Grade 3 (third occurrence) 
Grade 3 which does not recover to 
baseline or Grade 1 within 28 days 
Any Grade 4 
Permanently Discontinue 
N/A 
a   Eg, 1 dose level lower for patients treated at 20 mg/kg is 10 mg/kg; 1 dose level lower for patients treated at 
10 mg/kg is 3 mg/kg; 1 dose level lower for patients treated at 3 mg/kg is 1 mg/kg.  
There is a ± 3-day window for the first 3 scheduled FPA150 dosing visits. The first dose of 
each cycle is considered Day 1 of each cycle. Cycles will repeat every 21 days unless there is 
a treatment delay.  Intrapatient dose escalation will not be permitted above 1mg/kg except as 
detailed in Section 6.4.2. Any patient whose dose of FPA150 is decreased cannot be 
subsequently increased. 

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Dose Modification Criteria (Pembrolizumab) including Immune Related AEs 
Any dose modifications for pembrolizumab-related toxicity in patients enrolled on the 
Phase 1a Safety Lead-in will be considered a DLT and the patient will need to be replaced.  
Dose modifications for pembrolizumab in the Phase 1b dose expansion will be allowed in 
accordance with the Keytruda® USPI. Dose reductions for pembrolizumab are not permitted.  
AEs associated with pembrolizumab exposure may represent an immunologic etiology. These 
irAEs may occur shortly after the first dose or several months after the last dose of 
pembrolizumab treatment and may affect more than one body system simultaneously. irAEs 
may be managed with interruptions of pembrolizumab, administration of corticosteroids 
and/or other supportive care. Dose modification and toxicity management for irAEs 
associated with pembrolizumab should be done in accordance with the guidelines provided in 
the Keytruda® USPI. 
 
Dose Interruptions During Study Treatment Administration 
FPA150:  Infusion must be stopped if any AE ≥ Grade 3 occurs during the infusion. 
If bronchospasm or dyspnea occurs in a patient during the infusion, the infusion must be 
stopped.  
In addition, at the Investigator’s discretion, the infusion rate for FPA150 may be reduced or 
stopped if a less severe AE (Grade 1 or 2) occurs during the infusion. If a Grade 3 or less 
severe AE resolves within 4 hours, the infusion may be restarted at half the previous rate and 
promptly managed according to the discretion of the Investigator. If the same AE appears 
again with the same severity at any time during the restarted infusion, the infusion should be 
discontinued, and no further dosing of FPA150 will occur without consultation with the 
Sponsor or Sponsor’s designee. 
If a patient experiences an infusion reaction prior to completion of the infusion, the infusion 
must be stopped, and the patient should be promptly managed and monitored according to 
signs and symptoms, and local clinical protocol until there is a complete resolution of the 
event. Symptoms of infusion reactions may include: fever, chills, rigors, urticaria, 
hypotension and hypertension with headache, wheeze, breathlessness, hypoxia, and 
pulmonary infiltrates. For patients whose infusion-associated events were either Grade 1 or 2, 
and completely resolved on the day of the infusion, the infusion may be resumed at the 
discretion of the Investigator at a slower rate with premedication. All subsequent infusions for 
that patient should then be administered at the reduced rate of infusion with pre-medications. 
Pre-medications may include medications such as corticosteroids, diphenhydramine, 
acetaminophen and/or bronchodilators as indicated. FPA150 will be permanently discontinued 
for patients who have experienced Grade 3 or above infusion-associated AEs, and for patients 
who have recurrent infusion-associated reactions after restarting the infusion despite 
pre-medications and slower infusion. 

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If a patient experiences an infusion reaction, the patient’s vital signs (temperature, blood 
pressure, pulse, and respiration rate) should be monitored during the infusion, as well as every 
30 minutes after the infusion for a minimum of 2 hours and until resolution of the infusion 
reaction. 
Pembrolizumab:  Pembrolizumab may cause severe or life threatening infusion-reactions 
including severe hypersensitivity or anaphylaxis. Signs and symptoms usually develop during 
or shortly after drug infusion and generally resolve completely within 24 hours of completion 
of infusion. Dose modification and toxicity management for infusion reactions associated with 
pembrolizumab should be in accordance with the guidelines provided in the Keytruda® USPI. 
 
Maximum Duration of Treatment 
There is no pre-specified maximum number of doses of FPA150 monotherapy or in 
combination.  Patients may continue receiving FPA150 monotherapy according to their study 
specified cohort/dose until Investigator-assessed disease progression or the patient meets any 
of the other protocol-specified withdrawal criteria.   
Patients may receive pembrolizumab therapy according to their study specified cohort/dose 
until Investigator-assessed disease progression, the patient meets any of the other protocol-
specified withdrawal criteria or the patient completes approximately 24 months of 
pembrolizumab treatment.     
If one of the two drugs have to be discontinued, patients may continue to receive the other 
drug alone. 
 
Method of Treatment Assignment 
Patients in Phase 1a Dose Escalation will be sequentially assigned to dose levels at the time of 
enrollment, as described in Section 4.1.2 Patients in Phase 1a Dose Exploration will be 
assigned to the dose level and schedule selected based on the results of the Phase 1a Dose 
Escalation, as described in Section 4.1.3. Patients in Phase 1b Dose Expansion will be 
assigned to the dose level and schedule selected based on the results of the Phase 1a Dose 
Escalation and Phase 1a Dose Exploration, as described in Section 4.1.4. 
Procedures for informed consent, screening, and enrollment are outlined in Section 8.1. 
 
Blinding 
Blinding and breaking the blind are not applicable as this study is open label. 
 
Study Drug Accountability 
The Investigator or appropriately qualified staff is responsible for maintaining accurate study 
drug accountability records throughout the study. 

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The Investigator is responsible for returning all unused study drug to the Sponsor (or 
designee), and must verify that no remaining supplies are in the Investigator’s possession. 
The study site is permitted to destroy used or partially used study drug vials according to the 
site policy once Sponsor approval of their documented destruction procedure has been 
obtained. On completion of the study, the number of FPA150 and/or pembrolizumab vials 
shipped, destroyed, and returned must be reconciled. 
Details regarding preparation, storage, handling, and administration are provided in 
Sections 6.2 and 6.3. 
 
Treatment Compliance 
Only qualified study center personnel may administer FPA150 and/or pembrolizumab. 
Pharmacy personnel trained in the study requirements will monitor compliance with the 
treatment assignments. Records of study medication administered (date, time, and dose 
administered relative to time of preparation) will be recorded on the patient’s electronic case 
report form (eCRF). 
 
Concomitant Therapy 
Supportive care (eg, anti-emetics, analgesics for pain control, bisphosphonates and 
denosumab) may be used at the Investigator’s discretion and in accordance with institutional 
procedures. Hematopoietic stimulating agents may be used if indicated. Concomitant 
anti-cancer therapies of any kind are not permitted. 
Rescue and supportive care medications that are allowed with pembrolizumab should be given 
in accordance with the guidelines provided in the Keytruda® USPI. 
 
 
 

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7 
Discontinuation/ Withdrawal Criteria 
 
Discontinuation of Study Treatment 
Treatment with study drug may be discontinued for any of the following reasons: 
• Consent withdrawal at the request of the patient or their legally authorized representative 
• Progressive disease as assessed by the Investigator. Treatment beyond disease progression 
may be allowed in select patients with initial RECIST v1.1 defined progressive disease if 
the benefit/risk assessment favors continued administration of study treatment (eg, patients 
are continuing to experience clinical benefit as assessed by the Investigator, and tolerating 
treatment). 
• Any event that would pose an unacceptable safety risk to the patient 
• A concurrent illness that would affect assessments of the clinical status to a significant 
degree 
• A positive pregnancy test at any time during the study 
• 24 months of treatment with pembrolizumab 
• Specific request of the Sponsor or its authorized representative (eg, if the study is 
terminated for reasons of patient safety) 
• AE 
• Investigator decision 
• Patient decision, non-AE 
• Other 
 
Withdrawal from the Study 
Any patient may be discontinued from the study for any of the following reasons: 
• Consent withdrawal at the request of the patient or their legally authorized representative 
• AE 
• Death 
• Investigator decision 
• Lost to follow-up 
• Significant noncompliance to protocol 
• Study termination by Sponsor 
• Other 

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The Sponsor or its designee must be notified if a patient is withdrawn from study treatment or 
from the study. The reason(s) for withdrawal must be documented in the patient’s medical 
records and case report form (CRF). When a patient withdraws from treatment, all safety data 
normally required at the end of the study (ie, the EOT visit and long-term follow-up) will be 
obtained if possible. 
 
Patient Replacement 
Patients in Phase 1a Dose Escalation or Phase 1a Combination Safety lead-in will be replaced 
if they are unevaluable for DLT (refer to Section 4.1.2.2). Patients in Phase 1a Dose 
Exploration or Phase 1b Dose Expansion will not be replaced. 
 
Premature Termination of the Study 
If the investigator, Sponsor, or Medical Monitor becomes aware of conditions or events that 
suggest a possible hazard to patients if the study continues, the study may be terminated. 
The study may also be terminated early at the Sponsor’s discretion in the absence of such a 
finding. 
Conditions that may warrant termination include, but are not limited to: 
• Discovery of an unexpected, significant, or unacceptable risk to the patients enrolled in the 
study  
• Failure to enroll patients at an acceptable rate  
• Decision on the part of the Sponsor to suspend or discontinue development of the drug 
 
 

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8 
Study Assessments and Procedures 
Descriptions of assessments are provided in Sections 8.1 through 8.14, below. 
Additional guidance for study assessments and procedures is provided in the following 
appendices: 
• Specific timing requirements for study assessments and procedures: Appendix 1 
Schedule of Assessments. 
• Guidance for the specific timing of PK, immunogenicity, and pharmacodynamic sample 
collection: Appendix 2 Schedule of Pharmacokinetic, Immunogenicity, and 
Pharmacodynamic Blood Sample Collection.  
• Specific pharmacodynamic analyses to be conducted: Appendix 3 List of 
Pharmacodynamic Samples for Analyses. 
• Guidance for ECOG assessment: Appendix 4 Eastern Cooperative Oncology Group 
Performance Status. 
• Specific clinical laboratory tests to be conducted: Appendix 5 Clinical Laboratory Tests. 
• NYHA Classification: Appendix 6 New York Heart Association Classification.  
 
Informed Consent, Screening, and Enrollment 
Patients must be able to provide written informed consent and meet all eligibility criteria prior 
to enrollment.  
Only patients who meet all eligibility criteria outlined in Section 5 will be enrolled in this 
study. No waivers of inclusion or exclusion criteria will be granted by the Investigator and 
Sponsor or its designee for any patient enrolled in the study. Patients who qualify for Phase 1a 
of the study will be enrolled into the first available cohort. A patient may be enrolled into 
either Phase 1a or Phase 1b of the study, but not both. 
In both Phase 1a and 1b, the Investigator may repeat qualifying laboratory tests and vital 
signs/ ECGs prior to enrollment if a non-qualifying finding is considered an error, and/or if an 
acute finding is likely to meet eligibility criteria on repeat testing. Local hematology and 
blood chemistry test results must be obtained within 96 hours of dosing to confirm eligibility. 
Refer to Section 8.1.1 below for specific informed consent requirements by study phase. 

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Informed Consent Requirements by Study Phase 
All subjects in all monotherapy and combination therapy cohorts must sign and date the most 
recent IRB/IEC-approved informed consent form before any study procedures are performed.   
Optional procedures may require separate subject consent, either within the main ICF or on a 
separate ICF, per IRB/IEC requirements.  Subjects who screen fail must re-sign the informed 
consent, if any screening procedures will be performed outside of the 28-day screening 
window from the time of the first informed consent. 
 
Medical History and Demographics 
Patient medical and surgical history includes a thorough review of significant past medical 
and surgical history, current conditions, concomitant therapies, alcohol and smoking history, 
and smoking status.  
Demographics including age, gender, race, and ethnicity will be recorded. 
 
Safety Assessments  
Unless otherwise specified, all safety assessments must be completed prior to start of study 
drug infusion on scheduled dosing days in accordance with the Schedule of Assessments 
(Appendix 1). Safety measures will include vital signs, body weight, physical examination, 
ECOG performance status, laboratory tests (hematology, serum chemistries, and urinalysis), 
ECGs, and monitoring of AEs and concomitant medications.  
In Phase 1a, the CRC (refer to Section 4.1.1) will evaluate study safety data (AEs and serious 
adverse events [SAEs]) on a regular basis throughout the entire treatment phase (as described 
in the CRC Charter). 
 
Physical Examinations, Height and Weight 
A complete physical examination including height and weight will be performed at screening. 
A limited physical examination (eg, symptom-directed examination of specific organ systems/body 
area) should be conducted at the specified time points after screening in accordance with the 
Schedule of Assessments (Appendix 1). After Cycle 1, the FPA150 dose will be recalculated 
at each infusion visit only if the patient’s weight has changed > 10% from Cycle 1, Day 1. 
Weight will also be recorded at the final EOT visit. 
 
Vital Signs 
Vital signs (blood pressure, pulse, respiration, and temperature after 5 minutes of rest) will be 
measured in accordance with the Schedule of Assessments (Appendix 1). 

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Electrocardiograms 
Twelve-lead ECGs will be performed in accordance with the Schedule of Assessments 
(Appendix 1). To minimize variability, it is important that patients are in a resting position for 
at least 5 minutes prior to each ECG evaluation. Body position should be consistently 
maintained for each ECG to prevent changes in heart rate. ECGs for each patient should  be 
obtained from the same machine whenever possible. The ECGs should be reviewed promptly 
by a qualified physician and any clinically important finding should be recorded on the 
appropriate CRF. The Investigator is responsible for providing the interpretation of all ECGs. 
The results will include heart rate, PR interval, QRS interval, QT interval, and QTc interval. 
ECGs should be performed before the PK blood draw on days where both are done. 
Additional ECGs should be obtained at any time if serum creatine kinase (CK) or cardiac 
troponin is elevated, or if ECG is abnormal (excluding sinus tachycardia; ECGs should be 
obtained [if clinically indicated] until the abnormality is resolved or clinically stable). 
Additional ECGs may be obtained at any time, if clinically indicated (eg, in case of elevated 
creatinine kinase [CK] or troponin).  
Any clinically significant changes in ECGs that occur during the study should be reported as 
an AE in the eCRF. 
8.3.3.1 
Eastern Cooperative Oncology Group Performance Status 
ECOG performance status will be assessed in all patients in accordance with the Schedule of 
Assessments (Appendix 1). The ECOG performance scale is provided in Appendix 4 Eastern 
Cooperative Oncology Group Performance Status. 
The ECOG performance status is a scale used to assess how a patient's disease is progressing, 
assess how the disease affects the daily living abilities of the patient, and determine 
appropriate treatment and prognosis.  
 
Tumor Tissue 
Tumor tissue should be collected in accordance with the Schedule of Assessments 
(Appendix 1).  Requirements for archival tumor tissue and fresh biopsies by phase of study is 
detailed in Section 4.1. 
 
Archival Tissue 
Mandatory archival tumor tissue from an excisional, incisional or core needle biopsy (or 
patient must undergo a fresh tumor biopsy during screening if archival tissue is not available; 
fine needle aspirates or other cytology specimens are insufficient for downstream biomarker 
analyses) will be collected as follows: 

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• Archival tumor block (preferred) or 10 unstained sections from an archival tumor block 
must be provided during screening by all patients in the study for exploratory biomarker 
analyses 
• Five unstained sections from an archival tumor block must be provided during 
pre-screening from patients in the Phase 1a Monotherapy Dose Exploration, Phase 1a 
Combination Safety Lead-in, Phase 1b Monotherapy Dose Expansion, and Phase 1b 
Combination Dose Expansion for evaluation of B7-H4 expression by IHC. 
 
Procedures for Fresh Biopsy 
All patients in Phase 1a Monotherapy Dose Exploration cohorts,  and at least 15 patients per 
30 patient cohort in Phase 1b Dose Expansion cohorts (monotherapy and in combination with 
pembrolizumab) will be required to undergo a fresh tumor biopsy during screening and just 
prior to drug administration at Cycle 3.  For the patient’s convenience, the biopsy required 
prior to Cycle 3 Day 1 is flexible as long as the biopsy is obtained after Cycle 2 Day 15 and 
prior to study drug administration on Cycle 3 Day 1.  
The following guidelines apply to patients who consent for tumor biopsy: 
• All patients that consent to a pre-treatment biopsy must have at least one tumor site that 
can be biopsied and be willing to have pre-treatment and on-treatment biopsies, from the 
same lesion where feasible.  
• Patients in Phase 1a Monotherapy Dose Escalation who do not have archival tissue require 
a fresh tissue biopsy for enrollment. 
• Biopsies will be performed according to the treating institution’s own guidelines. These 
biopsies must be excisional, incisional or core needle biopsies, as fine needle aspirates or 
other cytology specimens are insufficient for downstream biomarker analyses. 
• If a pre-treatment biopsy has been performed as part of the patient’s standard of care 
within 28 days prior Cycle 1 Day 1 and the sample can be made available to study 
Sponsor, the pre-treatment biopsy does not need to be repeated.  
• Sites for biopsy must be distinct from target lesions used for efficacy assessment 
• Patient must have recovered from any acute adverse effects of the biopsy procedure prior 
to dosing 
 
Clinical Safety Laboratory Assessments 
Laboratory assessments will be performed in accordance with the Schedule of Assessments 
(Appendix 1). Laboratory assessments will be performed locally at each study center’s 
laboratory by means of their established methods. Before starting the study, the Investigator 
will provide the Sponsor (or designee) with a list of the normal ranges and units of 
measurement. Testing HbsAg, HbcAb and HCV RNA will be performed at screening and if 
clinically indicated on study. Blood samples should be taken using standard techniques. 

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Abnormal laboratory results that lead to a change in patient treatment management (eg, dose 
delay, requirement for additional medication or monitoring) are considered clinically 
significant for the purposes of this study and will be recorded on the AE page of the eCRF. 
Laboratory test values that meet SAE criteria must be reported as SAEs. Refer to 
Section 8.12.2 for details regarding the reporting of abnormal laboratory findings as AEs. 
If either AST or ALT is elevated, obtain total serum bilirubin and alkaline phosphatase; repeat 
daily or other interval, as clinically indicated, until resolved or stable. Additional tests to rule 
out drug-induced liver injury (eg, abdominal ultrasound, serum gamma- glutamyl transferase 
(GGT), hepatitis serology) may be obtained at any time, if clinically indicated. 
 
Efficacy Assessments 
 
Tumor Assessment 
The first on-study imaging assessment should be performed within 28 days from C1D1.  
Subsequent tumor assessments will be performed in accordance with the Schedule of 
Assessments (Appendix 1) and should consist of clinical examination and appropriate imaging 
techniques (preferably computed tomography (CT) scans with appropriate slice thickness per 
RECIST v1.1, magnetic resonance imaging (MRI) acceptable). The same methods used to 
detect lesions at baseline are to be used to follow the same lesions throughout the clinical 
study.  
Tumor response assessment will be performed every 6 weeks for 6 months and then every 
12 weeks by the Investigator per the Schedule of Assessments (Appendix 1) using RECIST 
v1.1 guidelines (Appendix 4) (Eisenhauer 2009).  
If patient terminates prior to scheduled CT/MRI scans, patient should have scans done at the 
EOT visits (does not need to be repeated if performed within 8 weeks prior to the EOT visits, 
or if tumor progression was previously determined). After discontinuation of study treatment 
for reasons other than progressive disease, or withdrawal of consent, or initiation of additional 
anti-cancer therapy, tumor assessments will continue approximately every 12 weeks until 
disease progression, withdrawal of consent or start of new anti-cancer therapy. 
 
Pregnancy 
Pregnancy testing (serum or urine) should be conducted in accordance with the Schedule of 
Assessments (Appendix 1).  
 
Pregnancy Testing 
Pregnancy is an exclusion criterion and women of child bearing potential must not be 
considering pregnancy during the study. Pregnancy tests should be performed for any woman 
of childbearing potential. Serum ß-hCG (evaluated by local laboratories) and urine pregnancy 
tests will be performed only on women of child bearing potential. 

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Pregnancy on Study 
In the event of suspected pregnancy, a serum pregnancy test should be repeated. Patients who 
become pregnant during the study must discontinue study treatment immediately. 
The Sponsor must be notified of any patient who becomes pregnant while participating in this 
study. Although pregnancy is not an AE, all pregnancies must be followed to conclusion to 
determine their outcome. It is the responsibility of the Investigator or designee to report any 
pregnancy in a patient that occurs during the study by completing the Pregnancy Reporting 
Form. Please contact the study monitor to receive the Pregnancy Reporting Form on learning 
of a pregnancy. 
Notification of the pregnancy including the anticipated date of birth should be submitted on a 
Pregnancy Reporting Form within 24 hours of awareness and reported using the same 
procedure as described for reporting SAEs (Section 8.12.6). If the pregnancy is to be 
terminated, the anticipated date of termination should be provided. 
The patient will be asked to provide information on the outcome of the pregnancy, including 
premature termination should the case arise. Spontaneous miscarriages, premature termination 
of the pregnancy, and congenital abnormalities will be reported as SAEs. Information on the 
status of the mother and child will be forwarded to the Sponsor. Follow-up will be in 
accordance with regulatory guidance and at least 6 to 8 weeks after the estimated delivery 
date.  
Pregnancies that occur during the first 6 months of the Follow-up period should be reported to 
the Sponsor, and followed as described above. 
Refer to https://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf for 
additional guidelines regarding pregnancy and contraception for pembrolizumab. 
 
Pharmacokinetics 
Samples for PK assessment will be collected and processed according to instructions provided 
in a separate laboratory manual. FPA150 concentration in serum will be determined using an 
enzyme linked immunosorbent assay (ELISA) method. Additional guidance for sampling and 
procedures is provided in Appendix 2. 
The PK parameters (AUC, Cmax, Ctrough, CL, t1/2, Vss ) for FPA150 will be derived from serum 
FPA150 concentration-time data using non-compartmental analysis (NCA) when appropriate 
and applicable. Alternative methods may be considered. Other parameters, such as dose 
proportionality, accumulation ratio, attainment of steady state, will also be calculated if the 
data are available. The impact of immunogenicity on FPA150 exposure will be assessed. 

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Samples for PK analysis for any of the cohorts of FPA150 in combination with 
pembrolizumab will be collected and held at a central laboratory. Individual and mean (±SD) 
serum concentration-time data for FPA150 and pembrolizumab may be tabulated and plotted 
by dose level/cohort.  PK parameters for the combination may be tabulated and summarized 
by dose level/cohort when appropriate and applicable.  
 
Pharmacodynamics 
Samples for pharmacodynamic assessment will be collected and processed according to 
instructions provided in a separate laboratory manual. Additional guidance for sampling and 
procedures is provided in the following appendices: 
• Specific timing requirements for study assessments and procedures: Appendix 1 Schedule 
of Assessments. 
• Guidance for the specific timing of pharmacodynamic sample collection: Appendix 2 
Schedule of Pharmacokinetic, Immunogenicity, and Pharmacodynamic Blood Sample 
Collection.  
• Specific pharmacodynamic analyses to be conducted: Appendix 3 List of 
Pharmacodynamic Samples for Analyses. 
Blood and tumor samples will be collected at baseline and on treatment for exploratory 
pharmacodynamic biomarker analysis, to determine the effect of study drug on target cells 
and target biology, and to confirm mechanism of action in human disease. 
 
Immunogenicity Assessments 
Samples for immunogenicity assessment will be collected and processed according to 
instructions provided in a separate laboratory manual. Additional guidance for sampling and 
procedures is provided in the following appendices: 
• Specific timing requirements for study assessments and procedures: Appendix 1 Schedule 
of Assessments. 
• Guidance for the specific timing of immunogenicity sample collection: Appendix 2 
Schedule of Pharmacokinetic, Immunogenicity, and Pharmacodynamic Blood Sample 
Collection.  
Immunogenicity, defined as an ADA immune response to FPA150, will be assessed by 
measurement of total anti-FPA150 antibodies from all patients. Immunogenicity testing will 
consist of screening, confirmation, and titration of anti-FPA150 antibodies. Additional 
characterization of a confirmed anti-FPA150 antibody response may be considered.  

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Immunogenicity, defined as an ADA immune response to pembrolizumab, will be assessed by 
measurement of total anti-pembrolizumab antibodies from all patients. Immunogenicity 
testing will consist of screening, confirmation, and titration of anti-pembrolizumab antibodies. 
Additional characterization of a confirmed anti-pembrolizumab antibody response may be 
considered. 
 
Predictive and Pharmacodynamic Biomarkers 
Samples for predictive and pharmacodynamic biomarker assessment will be collected and 
processed according to instructions provided in a separate laboratory manual. Additional 
guidance for sampling and procedures is provided in the following appendices: 
• Specific timing requirements for study assessments and procedures: Appendix 1 Schedule 
of Assessments. 
• Guidance for the specific timing of PK, immunogenicity, and pharmacodynamic sample 
collection: Appendix 2 Schedule of Pharmacokinetic, Immunogenicity, and 
Pharmacodynamic Blood Sample Collection.  
• Specific pharmacodynamic analyses to be conducted: Appendix 3 List of 
Pharmacodynamic Samples for Analyses. 
A variety of endpoints that could monitor drug activity and potentially predict clinical 
response to FPA150 may be investigated in peripheral blood and archival and/or fresh tumor 
specimens, collected from patients prior to and during treatment. Data from these analyses 
will be evaluated for association with response and/or safety data.  
Exploratory biomarker analysis will be conducted to investigate the relationship between 
baseline target levels, tumor immune phenotype, pharmacodynamic response within the tumor 
and in the periphery, and efficacy. 
 
Analysis of B7-H4 Expression  
Samples for analysis of B7-H4 expression will be collected and processed according to 
instructions provided in a separate laboratory manual. Additional guidance for sampling and 
procedures is provided in the following appendices: 
• Specific timing requirements for study assessments and procedures: Appendix 1 Schedule 
of Assessments. 
• Specific pharmacodynamic analyses to be conducted: Appendix 3 List of 
Pharmacodynamic Samples for Analyses. 
Five Prime has developed an IHC assay based on a monoclonal anti-B7-H4 antibody, whose 
specificity and sensitivity has been evaluated (refer to Section 2.2.1 for additional information 
regarding FPA150 and B7-H4). Baseline tumor samples (archival or recent biopsy if archival 
is not available) for B7-H4 expression by IHC must be available prior to enrollment for 

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patients in the Phase 1a Monotherapy Dose Exploration, Phase 1a Combination Safety Lead-in, 
Phase 1b Monotherapy Dose Expansion and Phase 1b Combination Dose Expansion cohorts.  
Archival tissue for patients enrolled in Cohort 1b1 (Breast Cancer) must be within 24 months 
prior to pre-screening. 
Because it is predicted that patients whose tumors have high levels of expression of the target 
B7-H4 protein are more likely to respond to FPA150, patients in the Phase 1a Dose 
Exploration,Phase 1a Combination Safety Lead-in, and in Phase 1b Dose Expansion will be 
selected based on B7-H4 expression by an IHC test.  
Prevalence studies conducted at Five Prime with the IHC assay using archival tissue has 
shown a variety of cancers express high levels of B7-H4 including breast, ovarian, 
endometrial and urothelial carcinoma.  
 
Tumor Marker 
 
Samples for tumor markers 
 will be collected and processed according 
to instructions provided in a separate laboratory manual. Additional guidance for sampling 
and procedures is provided in the following appendices: 
• Specific timing requirements for study assessments and procedures: Appendix 1 Schedule 
of Assessments. 
• Guidance for the specific timing of PK, immunogenicity, and pharmacodynamic sample 
collection: Appendix 2 Schedule of Pharmacokinetic, Immunogenicity, and 
Pharmacodynamic Blood Sample Collection.  

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• Specific pharmacodynamic analyses to be conducted: Appendix 3 List of 
Pharmacodynamic Samples for Analyses. 
Blood samples will be processed to collect plasma and stored frozen prior to analysis. In 
addition to the PK and ADA analyses, plasma samples may be analyzed to determine the 
pharmacodynamic effect of study drugs on
 or circulating tumor marker 
concentrations. Samples may be assessed by ELISA, seromics, and/or other relevant 
multiplex-based protein assay methods.  
 
Gene Expression Profiling 
Samples for gene expression profiling will be collected and processed according to 
instructions provided in a separate laboratory manual. Additional guidance for sampling and 
procedures is provided in the following appendices: 
• Specific timing requirements for study assessments and procedures: Appendix 1 Schedule 
of Assessments. 
• Guidance for the specific timing of PK, immunogenicity, and pharmacodynamic sample 
collection: Appendix 2 Schedule of Pharmacokinetic, Immunogenicity, and 
Pharmacodynamic Blood Sample Collection.  
• Specific pharmacodynamic analyses to be conducted: Appendix 3 List of 
Pharmacodynamic Samples for Analyses. 

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Whole blood and tumor tissue for exploratory biomarker analysis will be collected at the time 
points indicated in the Schedule of Assessments (Appendix 1)
 
 
 
 
 
Adverse Events 
Adverse events should be collected/ recorded in accordance with the Schedule of Assessments 
(Appendix 1). 
 
Method of Detecting and Reporting Adverse Events and Serious Adverse Events 
In Phase 1a and Phase 1b, any new symptoms, injury or worsening of symptoms that occur 
during the Screening Period, ie, following signing of the ICF but prior to first infusion 
(Cycle 1 Day 1), will be considered pretreatment events and reported on the Medical History 
page of the eCRF, unless they directly correlate to a study-related procedure in which case 
they will be reported on the AE eCRF page. Otherwise, AE reporting will begin at the time of 
infusion of Cycle 1, Day 1 (day of first infusion) and continue until completion of the End of 
Treatment visit or until 4 weeks (28 days) after the last dose of study treatment.  
Patients in Phase 1b will undergo long-term follow-up for survival by clinic visit or by 
telephone approximately every 3 months ± 28 days after the EOT visit until up to 24 months 
after the last patient is enrolled into the study.  
SAEs occurring after the EOT visit should be reported to the Sponsor by the Investigator only 
if the Investigator considers a causal relationship with FPA150. SAEs should always be 
recorded on the AE eCRF. 
 
Adverse Event Definitions 
An AE is any untoward medical occurrence that occurs in a patient administered a 
pharmaceutical product, and which does not necessarily have to have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and unintended sign (including 
abnormal laboratory finding), symptom, or disease temporally associated with the use of an 
IP, whether or not considered related to the product. Abnormal laboratory findings that are not 
considered clinically significant will be recorded only on the laboratory eCRF pages and not 
on the AE pages. Abnormal laboratory results that are considered clinically significant in the 
Investigator’s opinion are also to be recorded on the AE eCRF. Relationship (reasonable 
causal relationship) to drug therapy and counter measures undertaken will be noted on the 
eCRF. 
All AEs including intercurrent illnesses that occur during the study, from the time of 
administration of study treatment, will be documented on the AE eCRF. Concomitant 
illnesses, which existed prior to the day of the first study infusion, will not be considered AEs 

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unless they worsen by at least one grade during the treatment period. Intensity (severity) grade 
will be defined according to the NCI-CTCAE, version 4.03. Pre-existing conditions will be 
recorded on the Medical History eCRF. 
A treatment-emergent adverse event (TEAE) will be defined as an AE that begins or worsens 
in severity after at least one dose of study treatment (FPA150) has been administered. 
Diagnostic and therapeutic non-invasive and invasive procedures, such as surgery, will not be 
reported as an AE, but the procedure and/or therapeutic treatment should be recorded on the 
appropriate eCRF. The medical condition for which the procedure was performed must be 
reported as an AE (or as part of the patient’s medical history, if the procedure precedes the 
initiation of study-prescribed treatment). Disease progression is an efficacy endpoint and not 
an AE or SAE. Concurrent signs and symptoms clearly associated with disease progression 
itself should not be reported as an AE or SAE.  
 
Assessment of Adverse Events 
Each AE will be assessed by the Investigator with regard to seriousness, intensity (severity), 
causality and the outcome and action taken. All AEs, regardless of the relationship to study 
treatment, will be recorded on the AE eCRF. This includes potential end-organ toxicity, eg, 
renal (proteinuria), hepatic, and cardiovascular (increased blood pressure) effects, and effects 
on wound healing. All AE reports should contain a brief description of the event, date of 
onset, ongoing or date of resolution, intensity, treatment required, relationship to study 
treatment, action taken with the study treatment, outcome, and whether the event is classified 
as serious as described below. 
8.12.3.1 Serious Adverse Events 
An SAE is defined as any untoward medical occurrence that at any dose: 
• Results in death. Death may occur as a result of the underlying disease process. All events 
other than progression of underlying disease that result in death during the reporting 
period up to 28 days following the last dose of study treatment must be treated as an SAE 
and reported as such 
• Is life-threatening (patient is at immediate risk of death from the event as it occurred) 
• Requires inpatient hospitalization (formal admission to a hospital for medical reasons) or 
prolongation of existing hospitalization 
• Results in persistent or significant disability or incapacity 
• Is a congenital anomaly or birth defect 
Medically significant events that may not result in death, are not life-threatening, or do not 
require hospitalization may be considered SAEs when, based on appropriate medical 
judgment, they may jeopardize the patient and may require medical or surgical intervention to 

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prevent one of the outcomes listed in this definition. Examples of such events are intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency or drug 
abuse. 
Medical and scientific judgment should be exercised in deciding whether a case is considered 
medically significant or serious and whether expedited reporting is appropriate. 
Hospitalization for an event solely related to progressive disease is not considered an SAE. 
Hospitalization for an elective or planned procedure to treat a pre-existing condition is not 
considered an SAE unless it results in one of the outcomes listed above. 
8.12.3.2 Intensity (Severity) 
Investigators need to assess the severity of AEs according to the guidelines provided in 
NCI-CTCAE, version 4.03. 
CTCAE v 4.03 Severity Grades are: 
• Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated; mild AE 
• Grade 2: Moderate; minimal, local or non-invasive intervention indicated; limiting age-
appropriate instrumental activities of daily living; moderate AE 
• Grade 3: Severe or medically significant but non-immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
activities of daily living; severe AE 
• Grade 4: Life-threatening consequences; urgent intervention indicated 
• Grade 5: Fatal AE 
If the AE is not specified in the CTCAE or the study protocol, the grading of severity will be 
assessed as mild (Grade 1), moderate (Grade 2), severe (Grade 3), life-threatening (Grade 4), 
or death due to the AE (Grade 5) using the following definitions: 
• Mild: The patient is aware of the event or symptom, but the event or symptom is easily 
tolerated. 
• Moderate: The patient experiences sufficient discomfort to interfere with or reduce his or 
her usual level of activity. 
• Severe: Significant impairment of functioning: the patient is unable to carry out usual 
activities. 
• Very severe (life-threatening): The patient’s life is at risk from the event. 

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8.12.3.3 Causality 
The Investigator will assess the causality/relationship between the study treatment and the AE 
and record that assessment on the eCRF. 
The most likely cause of an SAE (eg, disease under treatment, concomitant disease, 
concomitant medication, other) will be indicated on the eCRF with details of the concomitant 
disease or medication or other cause. 
The causal relationship of the AE to study treatment will be assessed by means of a question: 
‘Is there a reasonable possibility that the AE may have been caused by the study treatment?’ 
Answer Yes or No. 
The description below provides guiding principles for the Investigator to make casualty 
assessments. 
• Yes, there is a reasonable possibility that the AE may have been caused by the study 
treatment: 
• Follows a reasonable temporal sequence from administration of the study treatment 
• Could not be reasonably explained by the patient’s clinical state, environmental or 
toxic factors, or other therapies administered to the patient 
• Disappears or decreases on cessation or reduction in dose of the study treatment 
• Follows a known pattern of response to the study treatment 
• Reappears or worsens on re-challenge 
• No, there is no reasonable possibility that the AE may have been caused by the study 
treatment: 
• Does not follow a reasonable temporal sequence from administration of the study 
treatment 
• Could be reasonably explained by the patient’s clinical state, environmental or toxic 
factors, or other therapies administered to the patient 
• Does not follow a known pattern of response to the study treatment 
• Does not reappear or worsen on re-challenge 
The relatedness for SAEs will also be assessed and documented on the AE eCRF. 

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8.12.3.4 Outcome and Action Taken 
The Investigator will record the action taken and outcome for each AE in the eCRF according 
to the following criteria: 
• Action Taken 
• Dose Not Changed 
• Drug Interrupted 
• Drug Withdrawn 
• Not Applicable 
• Unknown 
• Outcome 
• Fatal 
• Not Recovered/Not Resolved 
• Recovered/Resolved 
• Recovered/Resolved with Sequelae 
• Recovering/Resolving 
 
Follow-up of Adverse Events and Serious Adverse Events 
All treatment-related SAEs experienced by a study patient, will be monitored until the event 
has resolved or stabilized, any abnormal laboratory values have returned to baseline or 
stabilized at a level acceptable to the Investigator and Sponsor, there is a satisfactory 
explanation for the changes observed, or the patient is lost to follow-up. 
All unresolved AEs should be followed by the Investigator until the events are resolved, the 
patient is lost to follow-up, or the AE is otherwise explained. The Investigator should notify 
the study Sponsor of any death or AE occurring at any time after a patient has discontinued or 
terminated study participation that may reasonably be related to this study. The Sponsor 
should also be notified if the Investigator should become aware of the development of cancer 
or of a congenital anomaly in a subsequently conceived offspring of a patient that has 
participated in this study. 
 
Treatment of Overdose 
8.12.5.1 FPA150 
In the event of a medical emergency due to suspected FPA150 overdose the Medical Monitor 
should be contacted as soon as possible. Monitoring and reporting a suspected treatment 
overdose should follow guidelines for AEs and SAEs. No specific antidote is available for 

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treating overdose with FPA150. Management of any AEs due to overdose should be managed 
per Institutional practice. 
8.12.5.2 Pembrolizumab 
No specific information is available on the treatment of overdose of pembrolizumab. In the 
event of overdose, the patient should be observed closely for signs of toxicity. Appropriate 
supportive treatment should be provided if clinically indicated. 
 
Regulatory Reporting Requirements for Serious Adverse Events 
Any SAEs, whether or not considered related to treatment with FPA150, must be reported by 
the Investigator to the Sponsor or Sponsor’s designee within 24 hours of the Investigator 
becoming aware of the event and must be recorded on both the Electronic Serious Adverse 
Event Form (eSAE Form) and AE eCRF. Additional SAE information including medications 
or other therapeutic measures used to treat the event, action taken with the study treatment due 
to the event, and outcome/resolution of the event will be recorded on the eSAE form. Paper 
forms for reporting SAEs will also be provided to the study centers for SAE reporting in case 
the eSAE system is down.  
A digital copy of the eSAE form must be e-mailed within 24 hours to the attention of the 
ICON Pharmacovigilance Safety Specialist Email: icon-mads@iconplc.com: 
If the eSAE form is down or unavailable, the use of a paper SAE form or a digital copy is 
acceptable. The form must be faxed or emailed within 24 hours to the attention of the ICON 
Pharmacovigilance Safety Specialist: 
ICON Medical and Safety Services 
Fax number: +1-866-955-7492 
SAE Hotline: +1-888-723-9952  
icon-mads@iconplc.com 
The Investigator should not wait to receive additional information to fully document the event 
before notification of a SAE, though additional information may be requested. The minimum 
information that is required for an initial SAE report is as follows: 
• Patient number 
• Investigator name and study center number 
• Event term 
• Event onset date 
• Serious criteria 
• Relationship to study treatment(s) 

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As applicable, information from relevant laboratory results, hospital case records, and autopsy 
reports should be obtained. 
Serious AEs occurring after the EOT visit should be reported to the Sponsor by the 
Investigator if the Investigator considers there is a causal relationship with the study 
treatment.  
The Investigator and Sponsor will review each SAE report and evaluate the seriousness and 
causal relationship of the event to study treatment. In the event of a disagreement about 
causality, the most conservative assessment will be used. In addition, the Sponsor will 
evaluate the expectedness according to the FPA150 IB. Based on the Investigator and 
Sponsor’s assessment of the event, a decision will be made concerning the need for further 
action. 
The Sponsor or its designee is responsible for submitting reports of AEs associated with the 
use of the drug that are both serious and unexpected to the Food and Drug Administration 
(FDA), per 21 Code of Federal Regulations (CFR) 312.32, and to other regulatory authorities, 
according to national law and/or local regulations. All Investigators participating in ongoing 
clinical studies with the study medication will receive copies of these reports for prompt 
submission to their IRB or IEC.  
The Sponsor or its designee will submit all safety updates and periodic reports to the 
regulatory authorities as required by applicable regulatory requirements. 
 
Concomitant Medication Recording 
Concomitant medications should be collected/ recorded in accordance with the Schedule of 
Assessments (Appendix 1). 
All medications that were used from 14 days prior to enrollment through the end of study 
participation will be recorded in the eCRF. These are to include prescription and 
nonprescription medications, transfusions, vitamins and nutritional supplements, and other 
remedies. Excluded prior medications are excluded via the eligibility criteria (Section 5.2). 
Additional guidance regarding concomitant medication is provided in Section 6.10. 
 
End of Treatment Follow-Up 
End of treatment follow-up should be done in accordance with the Schedule of Assessments 
(Appendix 1). There is no pre-specified maximum number of doses of FPA150. Patients may 
continue receiving FPA150 as monotherapy according to their study specified cohort/ dose 
until Investigator-assessed disease, progression or the patient meets any of the other protocol-
specified withdrawal criteria (refer to Section 7).  Patients receiving pembrolizumab can 
continue receiving drug according to their study specified cohort/dose until Investigator-
assessed disease progression, the patient meets any of the other protocol-specified withdrawal 
criteria (refer to Section 7) or the patient completes approximately 24 months of treatment. 

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If one of the two drugs have to be discontinued, patients may continue to receive the other 
drug alone.  Treatment beyond disease progression may be allowed in select patients with 
initial RECIST v1.1 defined progressive disease if the benefit/risk assessment favors 
continued administration of study treatment (eg, patients are continuing to experience clinical 
benefit as assessed by the Investigator, and tolerating treatment). 
Each patient is required to complete an EOT follow-up period which will include visits at 
approximately 28 (±7) days and 100 (±7) days after the last dose (refer to Appendix 1). 
 
Long-Term Follow-Up 
Long-term follow-up should be done in accordance with the Schedule of Assessments 
(Appendix 1). Patients enrolled in Phase 1b will be required to enter into long-term follow-up 
after they have permanently discontinued study drug (refer to Section 7) until death, 
withdrawal of consent or study termination. During long-term follow-up, patients should be 
contacted every 12 (±2) weeks for survival status. Patients should have tumor scans every 
12 (±2) weeks, if tumor progression was not previously determined and/or use of alternative 
anti-cancer therapy has not been initiated. Any new anti-cancer therapy should be 
documented. 
 
 

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9 
Statistical Considerations  
Before database lock, a separate statistical analysis plan (SAP) will be finalized, providing 
detailed methods for the analyses outlined below.  
Any deviations from the planned analyses will be described and justified in the final 
integrated study report. 
 
Sample Size Determination  
For Phase 1a, this study is designed as a dose escalation study with objectives that include 
determination of an MTD and/or RD for FPA150 monotherapy and FPA150 combined with 
pembrolizumab.  It will also include assessments of the safety and tolerability of FPA150 
monotherapy and in combination with pembrolizumab. The sample size of this study was not 
determined by strict statistical considerations. The total number of patients planned for this 
study is estimated to be up to 278.  
Phase 1a will enroll up to 68 patients. The 68 patients include 23 to 26 patients in the Phase 1a 
Monotherapy Dose Escalation cohorts, 6 to 22 patients in the Phase 1a Combination Safety 
Lead-in cohort andup to 20 additional patients in the Phase 1a Monotherapy Dose Exploration 
cohorts to further evaluate safety, PK, pharmacodynamics, and clinical activity at 1 or more 
dose levels (to be conditional upon the dose level clearing DLT criteria).  
For the objective of estimating the ORR of FPA150 in the Phase 1b Monotherapy and 
Combination Dose Expansion cohorts, it is estimated that up to 30 patients will be enrolled to 
ensure 25 evaluable patients in each cohort. The following table displays the corresponding 
2-sided 90% confidence interval (CI) and the precision for the various observed response rates 
based on 25 evaluable patients. The sample size of 25 is chosen to ensure that it will allow to 
exclude 10% when the observed ORR is 24% or higher (Agresti 1998). 
Phase 1b will enroll up to 210 patients with specific tumor types. Up to 30 patients are 
planned for each of the 3 FPA150 Monotherapy Dose Expansion cohorts, and one additional 
cohort of FPA150 in combination with pembrolizumab. Additional cohorts of up to 
30 patients each may be enrolled, based on emerging clinical and translational data. 

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Table 11: 
Two-Sided 90% Confidence Intervals of the Observed Response Rates  
Sample Size 
Observed Response Rate 
90% CI 
Precision (longest one-sided 
CI length*) 
25 
5/25 (20%) 
(8%, 38%) 
18% 
6/25 (24%) 
(11%, 42%) 
18% 
7/25 (28%) 
(14%, 46%) 
18% 
8/25 (32%) 
(17%, 50%) 
18% 
9/25 (36%) 
(20%, 54%) 
18% 
10/25 (40%) 
(24%, 58%) 
18% 
Abbreviations: CI = confidence interval. 
*Distance from the observed response rate to the lower or upper CI boundary. 
Considering it is possible to open successive cohorts after data is reviewed, up to 210 patients 
may be enrolled in Phase 1b (not to exceed 30 patients in any individual cohort).  
A 2-stage design will be used to determine the actual enrolled subjects. Sponsor will evaluate 
efficacy in phase 1b on an ongoing basis and may suspend or terminate enrollment in specific 
cohorts if <=1 response (CR or PR per RECIST 1.1) is observed in the first 16 patients 
enrolled in each cohort. In this case, the probability of early termination is 0.81 with 0.05 
responder rate for futility and 0.2 responder rate for efficacy. 
 
Populations for Analyses 
The following analysis populations are defined for the study: 
• Safety Population—all patients who have received any portion of at least one dose of 
FPA150.  
• DLT-Evaluable Population—all patients enrolled into Phase 1 monotherapy and in 
combination with pembrolizumab who received at least two doses of FPA150 and 
completed Cycle 1 of treatment, or who experienced a DLT in Cycle 1.  
• Pharmcokinetic Full Analysis Population:  All patients who received at least one dose of 
FPA150 and had at least one FPA150 serum concentration result. 
• Pharmacokinetic -Evaluable Population—all patients in the PK Full Analysis Population 
who had sufficient PK sample for the calculation of at least one PK parameter on at least 
one Study Day.  
• Efficacy-Evaluable Population—all patients who met eligibility criteria, received at least 
one dose of FPA150, have measurable tumor lesions at baseline, and have at least 
one post-baseline disease assessment unless the death and clinical progressive disease 
occurred prior to the first post baseline disease assessment. 

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General Considerations 
All analyses will be descriptive and will be presented by phase, dose group, cohort and overall 
as appropriate. In addition, all patients dosed at the MTD and/or RD will also be summarized 
as appropriate. Data collected in this study will be presented using summary tables and patient 
data listings. Continuous variables will be summarized using descriptive statistics, specifically 
the number of valid cases, arithmetic mean, median, standard deviation (SD), minimum, and 
maximum. Categorical variables will be summarized by frequencies and percentages. 
A change to the data analysis methods described in the protocol will require a protocol 
amendment only if it alters a principal feature of the protocol. The SAP will be finalized prior 
to database lock. Any changes to the methods described in the final SAP will be described and 
justified in the clinical study report. 
 
Statistical Analyses 
 
Safety Analyses 
Safety analyses will be performed separately within both phases of the study and for all 
patients combined. Data from all patients that receive any portion of at least one dose of 
FPA150 as monotherapy or one dose of FPA150 in combination with pembrolizumab will be 
included in the safety analyses. AEs, clinical laboratory information, vital signs, ECOG 
performance status, weight, ECGs, and concomitant medications/procedures will be tabulated 
and summarized. In addition, the incidence of DLTs in Phase 1a will be summarized. 
Subject incidence of AEs will be summarized overall and with separate summaries for serious 
AEs, AEs leading to discontinuation, AEs leading to death, and NCI CTCAE Grade 3 or 
higher AEs. The patients’ worst grade for each preferred term will be used for the summary of 
AEs by CTCAE grade. Treatment-related AEs and SAEs will also be summarized similarly.  
Weight and vital signs will be summarized descriptively (N, mean, SD, median, minimum, 
and maximum). ECOG performance status will be summarized categorically and 
descriptively.  
Shift tables displaying patient counts and percentages classified by baseline grade and 
maximum grade on treatment will be provided for laboratory data by cohort and overall as 
appropriate.  
 
Efficacy Analyses 
The ORR will be summarized with frequencies and percentages with 90% CI by each 
dose/cohort. The duration of response (DOR) for complete response (CR) and partial response 
(PR) patients and PFS for all treated patients will be summarized with descriptive statistics 
(N, arithmetic mean, SD, median, minimum, and maximum). The ORR, DOR, and PFS will 

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be determined using RECIST v1.1. Kaplan-Meier methodology will be used to estimate 
median DOR and PFS and corresponding 95% CI. 
ORR, DOR, and PFS are defined below. 
ORR: defined as the total number of patients with confirmed responses of either CR or PR per 
RECIST v1.1 divided by the total number of patients who are evaluable for a response. 
DOR: defined as the time from onset of response (CR or PR) that is subsequently confirmed 
to the first observation of progressive disease or death due to any cause. Patients who are alive 
and progression-free at the time of data analysis will be censored at the time of their last 
assessment for tumor response. 
PFS: defined as the time from the patient’s first dose to the first observation of progressive 
disease or death due to any cause. Patients who are alive and progression-free at the time of 
data analysis will be censored at the time of their last assessment for tumor response.  
More details of censoring rule for DOR and PFS will be outlined in SAP. 
 
Pharmacokinetic Analyses 
Individual and mean (±SD) serum FPA150 concentration-time data from monotherapy or in 
combination with pembrolizumab will be tabulated and plotted by dose level. Estimated 
individual and mean (±SD) PK parameters (eg, AUC, Cmax, Cmin, CL, t1/2, Vss) will be 
tabulated and summarized by dose level. Other descriptive statistics might be reported for 
serum FPA150 when appropriate and applicable. 
For cohorts of FPA150 in combination with pembrolizumab samples for PK analysis will be 
collected and held at a central laboratory. Individual and mean (±SD) serum concentration-
time data for FPA150 and pembrolizumab may be tabulated and plotted by dose level/cohort.   
Other parameters, such as dose proportionality, accumulation ratio, and attainment of steady 
state, may be evaluated, tabulated, and summarized by dose level/cohort if the data is 
available. The impact of immunogenicity on FPA150 exposure will be assessed, tabulated, 
and summerized by dose level as data allow.  
 
Immunogenicity Analyses 
A baseline ADA-positive subject is defined as a subject who has an ADA positive sample at 
baseline. An ADA-positive subject is a subject with at least one ADA-positive sample relative 
to baseline after initiation of the treatment. The frequency distribution of baseline 
ADA-positive subjects and ADA-positive subjects after initiation of the treatment will be 
summarized for FPA150 and pembrolizumab, respectively. 

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Pharmacodynamic Analyses 
A list of potential pharmacodynamic analyses is provided in Appendix 3. Selected 
pharmacodynamic biomarkers will be assessed for meaningful changes between pretreatment 
and on-treatment tumor and peripheral blood samples. 
 
Interim Analyses  
Safety data will be reviewed on a routine basis by the Sponsor, contract research organization 
(CRO), and/or the CRC. In Phase 1a, the Sponsor (and/or designee) and Investigator(s) will 
review safety data from each dose cohort prior to dose escalation or de-escalation. AE data 
from the  treatment period following the DLT window will be presented to the Medical 
Monitors when available.  A 2-stage design will be used as described in Section 9.1. 
 
 

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10 Ethical, Legal, and Administrative Aspects 
 
Data Quality Assurance 
The Sponsor (or designee) may conduct a site visit prior to study initiation at a site to verify 
the qualifications of each investigator, inspect the site facilities, and inform the investigator of 
responsibilities and for ensuring study compliance and procedures for adequate and correct 
documentation.  
The investigator is required to prepare and maintain adequate and accurate case histories 
designed to record all observations and other pertinent data for each study patient. All 
information recorded on the eCRFs for this study must be consistent with the patients’ source 
documentation (ie, medical records). 
 
Electronic Case Report Forms and Source Documentation 
All data obtained during this study should be entered in the eCRFs promptly. All source 
documents from which eCRF entries are derived should be placed in the patient’s medical 
records. eCRF fields for which source documents will typically be needed include laboratory 
assessments, physical examination reports, nursing notes, ECG recordings, hospital records, 
CT scans, and/or MRI) reports.  
The eCRFs for each patient will be checked against source documents at the study site by the 
site monitor. Instances of missing or uninterpretable data will be discussed with the 
investigator for resolution.  
 
Access to Source Data 
During the study, a monitor will perform routine site visits to review protocol compliance, 
compare eCRFs and individual patient’s medical records, assess drug accountability, and 
ensure that the study is being conducted according to pertinent regulatory requirements. eCRF 
entries will be verified with source documentation. The review of medical records will be 
performed in a manner to ensure that patient confidentiality is maintained.  
In accordance with ICH Good Clinical Practices (GCP) guidelines, the investigator must 
ensure provision of sufficient time, reasonable space, and adequate qualified personnel for the 
monitoring visits. The visits are for the purpose of verifying adherence to the study protocol 
and the completeness, consistency, and accuracy of data entered on the eCRF and other 
documents. Moreover, regulatory authorities, IRBs, IECs, and/or the Sponsor’s Quality 
Assurance group may wish to carry out such source data checks and/or on-site audit 
inspections. Direct access to source data will be required for these inspections and audits; they 
will be carried out giving due consideration to data protection and medical confidentiality. 
The investigator assures that the Sponsor and/or Sponsor’s designee will receive the necessary 
support to complete these activities. 

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All participating centers should take particular care in ensuring that original imaging source 
data (CT images, MRI images, echo images, etc.) are maintained and accessible for 
monitoring, and that these original source data are then archived on a long-term basis in 
compliance with ICH GCP Section 8. These images must be stored in a secure location until 
the Sponsor or Sponsor’s designee authorizes their destruction, and must be retrievable by 
study patient number in the event of an audit. 
 
Data Processing 
The Data Management Plan, to be developed during the initiation phase of the study, will 
include specifications for consistency and plausibility checks on data and will also include 
data-handling rules for obvious data errors. All processes for data processing and query 
handling will be described in the Data Management Plan. 
 
Archiving Study Records 
Each study site will maintain a study file, which should contain, at minimum, the IB, the 
protocol and any amendments, the protocol for tissue sampling, drug accountability records, 
correspondence with the IEC/IRB and the Sponsor (or designee), and other study-related 
documents. 
The investigator agrees to keep records and those documents that include (but are not limited 
to) the identification of all participating patients, medical records, study-specific source 
documents, source worksheets, all original signed and dated ICFs, copies of all eCRFs, query 
responses, and detailed records of drug disposition to enable evaluations or audits from 
regulatory authorities and the Sponsor or its designees. 
The investigator shall retain records required to be maintained for a period of 5 years 
following the date a marketing application in an ICH region is approved for the drug for the 
indication for which it is being investigated or, if no application is to be filed or if the 
application is not approved for such indication, until at least 5 years after the investigation is 
discontinued. However, these documents should be retained for a longer period if required by 
the applicable regulatory requirement(s) or if needed by the Sponsor. In addition, the 
investigator must make provision for the patients’ medical records to be kept for the same 
period of time.  
No data should be destroyed without the agreement of the Sponsor. Should the investigator 
wish to assign the study records to another party or move them to another location, the 
Sponsor must be notified in writing of the new responsible person and/or the new location. 
Patients’ medical records and other original data will be archived in accordance with the 
archiving regulations or facilities of the investigational site. 

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Good Clinical Practice 
The procedures set out in this study protocol are designed to ensure that the Sponsor and 
investigator abide by GCP guidelines of the ICH and the Declaration of Helsinki (1989). The 
study also will be carried out in compliance with local legal requirements. 
 
Informed Consent 
All information about the clinical study, including the patient information and the ICFs, is 
prepared and used for the protection of the human rights of the patient according to ICH GCP 
guidelines and the Declaration of Helsinki. 
The ICFs, prepared by the investigator with the assistance of the Sponsor, must be approved 
along with the study protocol by the IEC/IRB and be acceptable to the Sponsor before each 
patient is enrolled on the study; written informed consent will be obtained according to the 
regulatory and legal requirements. Copies of the signed ICFs will be retained by the patient 
and the original will be filed in the investigator’s study center file, unless otherwise agreed. 
The investigator will not undertake any investigation specifically required only for the clinical 
study until valid consent has been obtained. The terms of the consent and when it was 
obtained must be documented in the source documents and in the eCRF. 
If a protocol amendment is required, the ICFs may need to be revised to reflect the changes to 
the protocol. If the consent form is revised, it must be reviewed and approved by the 
appropriate IRB/IEC and signed by all patients subsequently enrolled in the study as well as 
those currently enrolled in the study. 
 
Protocol Approval and Amendment 
Before the start of the study, the study protocol and/or other relevant documents will be 
approved by the IRB/IEC, in accordance with local legal requirements. The Sponsor, 
Sponsor’s agents, and investigator must ensure that all ethical and legal requirements have 
been met before the first patient is enrolled in the study.  
This protocol is to be followed exactly. To alter the protocol, amendments must be written, 
receive approval from the appropriate personnel, and receive IRB/IEC approval prior to 
implementation. The protocol amendment will be submitted to the IND application / Clinical 
Trial Application under which the study is being conducted. 
 
Clinical Study Report and Publications  
The data collected during this study are confidential and proprietary to FivePrime. Any 
publications or abstracts arising from this study require approval by FivePrime prior to 
publication or presentation and must adhere to the Sponsor’s publication requirements as set 
forth in the approved clinical trial agreement (CTA). All draft publications, including 
abstracts or detailed summaries of any proposed presentations, must be submitted to the 

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Sponsor at the earliest practicable time for review, but in any event not less than 30 days 
before submission or presentation unless otherwise set forth in the CTA. FivePrime shall have 
the right to delete any confidential or proprietary information contained in any proposed 
presentation or abstract and may delay publication for up to 60 days for purposes of filing a 
patent application. 
 Confidentiality 
All study findings and documents will be regarded as confidential. The investigator and 
members of his/her research team must not disclose such information without prior written 
approval from the Sponsor. 
The anonymity of participating patients must be maintained. Patients will be identified on 
eCRFs and other documents submitted to the Sponsor or Sponsor’s designee by their patient 
number, initials, and/or birth date. Study patients are not to be identified by name, and any 
information sent to the Sponsor or Sponsor’s designee should have patient identifiers 
redacted, and replaced with patient identification. Documents that include the name of the 
patient (eg, the signed informed consent) must be maintained in confidence by the 
investigator. The investigator further agrees to take all reasonable precautions to prevent the 
disclosure by any employee or agent of the study center to any third party or otherwise into 
the public domain.  
 Other Ethical and Regulatory Issues 
If a significant safety issue is identified, either from an individual case report or review of 
aggregate data, then the Sponsor will issue prompt notification to applicable regulatory 
authorities and investigators. Investigators will then notify local IRB/IECs as deemed 
appropriate based on individual IRB/IEC policy. A significant safety issue is one that has a 
significant impact on the course of the clinical trial or program (including the potential for 
suspension of the trial program or amendments to protocols) or warrants immediate update of 
informed consent. 

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11 References 
Adams, S., S. Loi, D. Toppmeyer, et al. 2017. "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." Journal of Clinical Oncology. 
http://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.1088#affiliationsContainer. 
Aghajanian, C., M. Sill, K. Darcy, et al. 2011. "Phase II Trial of Bevacizumab in Recurrent or 
Persistent Endometrial Cancer: A Gynecologic Oncology Group Study."  Journal of 
Clinical Oncology 29 (16):2259-2265. 
Agresti, A. and B. Coull. 1998. "Approximate is Better than "Exact" for Interval Estimation of 
Binomial Proportions."  The American Statistician 52 (2):119-126. 
Cortes, J., J. O'Shaughnessy, D. Leosch, et al. 2011. "Eribulin Monotherapy Versus Treatment 
of Physician's Choice in Patients with Metastatic Breast Cancer (EMBRACE): A 
Phase 3 Open-Label Randomised Study."  Lancet 377:914-923. 
Eisenhauer, E. A., P. Bogaerts, L. H. Schwartz, et al. 2009. "New Response Evaluation 
Criteria in Solid Tumours: Revised RECIST Guideline (version 1.1)."  European 
Journal of Cancer 45:228-247. 
Fan, M., Q. Zhuang, Y. Chen, et al. 2014. "B7-H4 Expression is Correlated with Tumor 
Progression and Clinical Outcome in Urothelial Cell Carcinoma."  Int J Clin Exp 
Pathol 7 (10):6768-6775. 
Fumoleau, P., R. Largillier, C. Clippe, et al. 2004. "Multicentre, Phase II Study Evaluating 
Capecitabine Monotherapy in Patients with Anthracycline- and Taxane-Pretreated 
Metastatic Breast Cancer."  European Journal of Cancer 40:536-542. 
Hamanishi, J., M. Mandai, T. Ikeda, et al. 2015. "Safety and Antitumor Activity of Anti-PD-1 
Antibody, Nivolumab, in Patients with Platinum-Resistant Ovarian Cancer."  Journal 
of Clinical Oncology 33 (34):4015-4022. 
Hanker, L., S. Loibl, N. Buchardi, et al. 2012. "The Impact of Second to Sixth Line Therapy 
on Survival of Relapsed Ovarian Cancer After Primary Taxane/ Platinum-Based 
Therapy."  Annals of Oncology 23:2605-2612. 
He, C., H. Qiao, H. Jiang, et al. 2011. "The Inhibitory Role of B7-H4 in Antitumor Immunity: 
Association with Cancer Progression and Survival."  Clinical and Developmental 
Immunology 2011:1-8. 
Kryczek, I., S. Wei, G. Zhu, et al. 2007. "Relationship Between B7-H4, Regulatory T Cells, 
and Patient Outcome in Human Ovarian Carcinoma."  American Association for 
Cancer Research 67 (18):8900-8905. 
Liu, W., Y. Chen, S. Zhu, et al. 2014. "B7-H4 Expression in Bladder Urothelial Carcinoma 
and Immune Escape Mechanisms."  Oncology Letters 8:2527-2534. 
Martin, M., A. Ruiz, M. Munoz, et al. 2007. "Gemcitabine Plus Vinorelbine Versus 
Vinorelbine Monotherapy in Patients with Metastatic Breast Cancer Previously 
Treated With Anthracyclines and Taxanes: Final Results of the Phase III Spanish 
Breast Cancer Research Group (GEICAM) Trial."  Lancet Oncology 8:219-225. 

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Miyatake, T., B. Tringler, W. Liu, et al. 2007. "B7-H4 (DD-O110) is Overexpressed in High 
Risk Uterine Endometrioid Adenocarcinomas and Inversely Correlated with Tumor T-
Cell Infiltration."  Gynecologic Oncology 106:119-127. 
Pujade-Lauraine, E., F. Hilpert, B. Weber, et al. 2014. "Bevacizumab Combined with 
Chemotherapy for Platinum Resistant Recurrent Ovarian Cancer: The AURELIA 
Open-Label Randomised Phase III Trial."  Journal of Clinical Oncology 32 (13):1302-
1308. 
Saber, H., R. Gudi, M. Manning, et al. 2016. "An FDA Oncology Analysis of Immune 
Activating Products and First-In-Human Dose Selection."  Regulatory Toxicology and 
Pharmacology 81:448-456. 
Schmid, P., S. Adams, H. S. Rugo, et al. 2018. "Atezolizumab and Nab-Paclitaxel in 
Advanced Triple-Negative Breast Cancer."  N Engl J Med 379 (22):2108-2121. 
Simon, I., D. Katsaros, I. Rigault de la Longrais, et al. 2007. "B7-H4 is Over-Expressed in 
Early-Stage Ovarian Cancer and is Independent of CA125 Expression."  Gynecologic 
Oncology 106:334-341. 
 
 

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12 Appendices 
The following appendices are provided for this protocol. 
APPENDIX 1:  
SCHEDULE OF ASSESSMENTS ........................................................... 113 
APPENDIX 2:  
SCHEDULE OF PHARMACOKINETIC, IMMUNOGENICITY, 
AND PHARMACODYNAMIC BLOOD SAMPLE COLLECTION ..... 117 
APPENDIX 3:  
LIST OF POTENTIAL PHARMACODYNAMIC SAMPLES FOR 
ANALYSES .............................................................................................. 119 
APPENDIX 4:  
EASTERN COOPERATIVE ONCOLOGY GROUP 
PERFORMANCE STATUS ..................................................................... 120 
APPENDIX 5:  
CLINICAL LABORATORY TESTS ....................................................... 121 
APPENDIX 6:  
NEW YORK HEART ASSOCIATION CLASSIFICATION .................. 123 
APPENDIX 7:  
PROTOCOL AMENDMENT HISTORY ................................................ 124 
 
 
 

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APPENDIX 1:  
SCHEDULE OF ASSESSMENTS  
Table 12: 
Schedule of Assessments: Phase 1a and Phase 1b (Monotherapy and Combination Cohorts) 
Procedurea,b 
Pre- 
Screening 
Screening 
Cycle 1 
Cycle 2 
Subsequent 
Cycles 
End of Treatment 
Follow-up Period 
LTFU 
Periodp 
Day –28 to 
Day 0 
Day 1q 
± 3 days 
Day 8 
± 3 days 
Day 1 
± 3 days 
Day 1 
± 3 days 
28 (±7) 
days post-
last dose 
100 (±7) 
days post-
last dose 
Informed Consent 
xi 
x 
 
 
 
 
 
 
 
Review / Confirm Eligibility Criteria 
 
x 
x 
 
 
 
 
 
 
Medical History / Demographics 
 
x 
x 
 
 
 
 
 
 
Physical Examinationc 
 
x 
x 
x 
x 
x 
x 
x 
 
Height and Weightc,d 
 
x 
x 
 
x 
x 
x 
x 
 
Vital Signse 
 
x 
x 
x 
x 
x 
x 
x 
 
12-Lead ECGf 
 
x 
 
 
 
 
x 
x 
 
ECOG Performance Statusg 
 
x 
x 
 
x 
x 
x 
x 
 
Fresh Biopsyh 
 
x 
 
 
 
x 
 
 
 
Archival Tissue for IHC Testing for 
B7-H4 and Exploratory Biomarker 
Analysesi 
x 
x 
 
 
 
 
 
 
 
Clinical Safety Laboratory Testsj 
 
x 
x 
x 
x 
x 
x 
x 
 
Hepatitis B (HBsAg and HBcAb), 
and Hepatitis C (HCV RNA) 
 
x 
 
 
 
 
 
 
 
CT/MRI Tumor Assessmentk, 
 
x 
 
 
 
x 
x 
 
x 
Tumor Markers l 
Refer to Appendix 2 for specific days and times 
Pregnancy Testm 
 
x 
x 
 
 
x 
x 
 
 
Sampling for PK, ADA, and 
Pharmacodynamicsn 
Refer to Appendix 2 for specific days and times  

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Procedurea,b 
Pre- 
Screening 
Screening 
Cycle 1 
Cycle 2 
Subsequent 
Cycles 
End of Treatment 
Follow-up Period 
LTFU 
Periodp 
Day –28 to 
Day 0 
Day 1q 
± 3 days 
Day 8 
± 3 days 
Day 1 
± 3 days 
Day 1 
± 3 days 
28 (±7) 
days post-
last dose 
100 (±7) 
days post-
last dose 
Study Drug(s)o  
 
 
x 
 
x 
x 
 
 
 
Adverse Eventss 
 
 
x 
x 
x 
x 
x 
 
 
Prior/Concomitant Medications 
 
 
x 
x 
x 
x 
x 
 
 
Thyroid Function Testingr 
 
 
x 
 
 
x 
 
 
 
Long-Term Follow-up Contactp 
 
 
 
 
 
 
 
 
x 
Abbreviations (for the Schedule of Assessments and Footnotes): ADA = anti-drug antibody; AE = adverse events; ALT = alanine transaminase; AST = aspartate 
transaminase; B7-H4 = transmembrane protein of the B7 family also known as B7S1, B7x, or VTCN1; CK = creatinine kinase; CT = computerized tomography; 
DOR = duration of response; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EOT = End of Treatment; HBsAg = hepatitis B surface 
antigen; HCV = hepatitis C antibody; IV = intravenous; LTFU = long-term follow-up; MRI = magnetic resonance imaging; PK = pharmacokinetics; 
Q3W = once every 3 weeks; Q12W = once every 12 weeks; RECIST v1.1 = Response Evaluation Criteria in Solid Tumors version 1.1. 
Additional guidance for sampling and procedures is provided in the following appendices: 
• 
Guidance for the specific timing of PK, immunogenicity, and pharmacodynamic sample collection: Appendix 2 Schedule of Pharmacokinetic, 
Immunogenicity, and Pharmacodynamic Blood Sample Collection.  
• 
Specific pharmacodynamic analyses to be conducted: Appendix 3 List of Pharmacodynamic. 
• 
Guidance for ECOG assessment: Appendix 4 Eastern Cooperative Oncology Group Performance Status. 
• 
Specific clinical laboratory tests to be conducted: Appendix 5 Clinical Laboratory Tests. 
• 
NYHA Classification: Appendix 6 New York Heart Association Classification. 
Footnotes for Schedule of Assessments (additional assessment and procedure details are provided in Protocol Section 8): 
a. Unless specified, procedure is to be completed within ± 72 hours of scheduled time point and performed prior to administration of study drug. 
b. Any clinical assessment, laboratory test, or additional non-specified test may be obtained at any time, if clinically indicated. 
c. A complete physical examination including height and weight will be performed at screening. A limited physical examination (e.g., symptom-directed 
examination of specific organ systems/body area) should be conducted at the specified time points after screening.  

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d. Height is only required to be recorded at screening. Weight is required to be recorded pre-dose at Day 1 of each cycle. After Cycle 1, the FPA150 dose will 
be recalculated at each infusion visit only if the patient’s weight has changed > 10% from Cycle 1, Day 1. Weight will also be recorded at the final EOT 
visit. 
e. Vital signs include pulse, respiratory rate, blood pressure, and temperature in a resting position. Measure vital signs prior to dosing and after completion of 
each IV infusion at the following time points: 5 minutes (± 3 min), 15 minutes (± 3 min), 30 minutes (± 3 min), and 1 hour post-dose (± 15 min). In addition, 
measure vital signs at 2, 3 and 4 hours post-dose (± 15 min) in patients that are being monitored for up to 4 hours post-dose (ie, after 1st infusion of FPA150 or 
after the end of infusion at each intrapatient dose escalation).  
f. 
The exact time of the ECG should be recorded. The results will include heart rate, PR interval, QRS interval, QT interval, and QTc interval. Additional ECGs 
should be obtained at any time, if serum CK or cardiac troponin is elevated; if abnormal (excluding sinus tachycardia), ECGs should be obtained (if clinically 
indicated), until the abnormality is resolved or clinically stable. Additional ECGs may be obtained at any time, if clinically indicated. ECGs for each patient 
should be obtained from the same machine whenever possible. ECGs should be performed before the PK blood draw on days where both are done. To 
minimize variability, it is important that patients be in a resting position for at least 5 minutes prior to each ECG evaluation. Body position should be 
consistently maintained for each ECG evaluation to prevent changes in heart rate. Environmental distractions (eg, television, radio, conversation) should be 
avoided during the pre-ECG resting period and during ECG recording. Any clinically significant changes in ECGs that occur during the study should be 
reported as an AE in the eCRF. 
g. ECOG status is to be assessed at Screening, within 72 hours prior to dosing on Day 1 of each cycle, and at EOT. 
h. A biopsy will be collected from the primary tumor or metastatic tumor site in patients enrolled in Phase 1a Monotherapy Dose Exploration, and a subset of 
patients (15 patients per 30-patient dose cohort) in Phase 1b Monotherapy Dose Expansion and Phase 1b Combination Dose Expansion cohorts; this will be 
done at screening and prior to the Cycle 3, Day 1 dose, from the same lesion where feasible. Refer to Section 8.4 for details regarding analyses of tumor 
tissue (fresh or archival). 
i. 
B7-H4 expression results must be available prior to enrollment for all patients in Phase 1a Monotherapy Dose Exploration, Phase 1a Combination Safety 
Lead-in, and all patients in Phase 1b Dose Expansion (monotherapy and in combination with pembrolizumab). Archival tissue for patients enrolled in Cohort 
1b1 (Breast cancer) must be within 24 months prior to pre-screening.  Five unstained sections from an archival tumor block must be provided during 
pre-screening of patients in Phase 1a Dose Exploration and in Phase 1b Dose Expansion for evaluation of B7-H4 expression by IHC. Archival tumor block 
(preferred) or 10 unstained sections from an archival tumor block must be provided during screening in all patients for exploratory biomarker analyses.  
j. 
Refer to Appendix 5 for a listing of all Clinical Safety Laboratory Tests to be conducted. Local hematology and blood chemistry test results must be 
obtained within 96 hours of dosing to confirm eligibility. All serum chemistries will be assessed locally.  
k. CT/MRI of the tumor sites should be measured according to RECIST v1.1. Tumor assessment should be performed at screening, then every 6 weeks [±1] 
week for the first 6 months for patients who remain on treatment (and every 12 [±2] weeks, thereafter). If patient terminates prior to scheduled CT/MRI scans, 
patient should have scans done at the EOT visits (does not need to be repeated if performed within 6 weeks prior to the End of Treatment visits, or if tumor 
progression was previously determined). Patients who enter LTFU while showing clinical benefit should have tumor assessments Q12W for DOR. The same 
measuring modality should be used by the site to maintain consistency across the various time points. 
l. 
Tumor markers will be assessed at a central laboratory. Tumor markers will be collected Day 1 of Cycles 1, 2, 3, 4, 5, 7, and 9.  After Cycle 9 tumor markers 
will be collected every 12 weeks (every 4 cycles). Tumor markers will be collected at the times noted in Appendix 2. 

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m. All women of childbearing potential (including those who have had a tubal ligation) will have a serum pregnancy test at screening. A serum or urine 
pregnancy test will be performed at Cycle 1 Day 1 and every 6 weeks during treatment, and at the EOT visits. 
n. 
Samples will be collected for PK, ADA, and pharmacodynamic analyses. All ADA and all PK samples should be collected prior to dosing. Not all visits will 
require collection of all 3 samples (PK, ADA, and Pharmacodynamic); refer to Appendix 2 for the collection schedule; refer to Appendix 3 for a list of the 
pharmacodynamic analyses. FPA150 samples for PK, ADA, and pharmacodynamic analyses will be assessed at a central laboratory. For cohorts of FPA150 
in combination with pembrolizumb samples for PK will be collected and held at a central laboratory.  In addition to the visits noted in Schedule of 
Assessments, PK and PD samples will be drawn on Day 4 and PK samples will be drawn on Day 15 of Cycle 1 for all cohorts. 
o. 
FPA150 will be administered as a 60-minute (± 5 minutes) IV infusion Q3W in 21-day cycles until progressive disease or unacceptable toxicity.  For 
FPA150 in combination with pembrolizumab cohorts, pembrolizumab will be administered after completion of the FPA150 IV infusion. Pembrolizumab will 
be administered at a dose of 200 mg by IV infusion over 30 minutes (± 5 minutes) starting on C1D1 and repeated Q3W on Day 1 of each 21-day cycle after 
all procedures and assessments have been completed. Pembrolizumab should not be co-administered with FPA150 through the same IV line. All patients 
must be monitored for at least 4 hours after the end of the first infusion of FPA150 and/or pembrolizumab. Patients may continue receiving FPA150 
monotherapy or both drugs in combination according to their study specified cohort/dose until Investigator-assessed disease progression or the patient meets 
any of the other protocol-specified withdrawal criteria (refer to Section 7)  
p. 
Only applicable for patients enrolled in Phase 1b cohorts, or the patient completes approximately 2 years of pembrolizumab. If one of the two drugs have to 
be discontinued, patients may continue to receive the other drug alone (based on Investigator discretion). Patients should be contacted every 12 (±2) weeks 
for survival status for up to 2 years. Patients should have tumor scans every 12 (±2) weeks, if tumor progression was not previously determined and/or use of 
alternative anti-cancer therapy has not been initiated. Any new anti-cancer therapy should be documented. 
q. 
To minimize lab draws for patients, any labs obtained during screening that fall within the window of 3 days prior to C1D1 can be used for dosing purposes.   
r. 
Thyroid function testing should be performed every 6 weeks while on treatment. Thyroid panel should include: Triiodothyronine (T3) or Free 
Triiodothyronine (FT3), Free thyroxine (FT4), and Thyroid stimulating hormone (TSH).  Safety labs are done locally. 
s. 
Adverse events should be collected only through the EOT Day 28 visit. 
 

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APPENDIX 2:  
SCHEDULE OF PHARMACOKINETIC, IMMUNOGENICITY, AND 
PHARMACODYNAMIC BLOOD SAMPLE COLLECTION 
Table 13: 
Schedule of Pharmacokinetic, Immunogenicity, and Pharmacodynamic 
Blood Sample Collection 
Study Cycle 
Study Day 
Time Point 
Type of Sample 
Screening 
Screening 
(Day-28) 
Screening 
Tumor Biopsy 
Cycle 1 
Day 1 
Prior to infusion 
FPA150 and/or pembrolizumab PK (serum) (≤ 4 hours 
prior to dosing) 
FPA150 and/or pembrolizumab ADA (serum)  
FPA150 and/or pembrolizumab pharmacodynamics, 
(plasma) 
 
FPA150 and/or pembrolizumab pharmacodynamics, 
 
FPA150 and/or pembrolizumab pharmacodynamics, 
 
 
FPA150 and/or pembrolizumab pharmacodynamics, 
  
FPA150 and/or pembrolizumab Tumor Markers (serum) 
15 minutes after end 
of infusion 
FPA150 and/or pembrolizumab PK (serum) (± 10 min) 
4 hours after end of 
infusion 
FPA150 PK (serum) (± 30 min) 
Day 2 
24 hours after end of 
infusion ± 3 hours 
FPA150 PK (serum) 
Day 4 
72 hours after end of 
infusion ± 3 hours 
FPA150 PK (serum) 
FPA150 pharmacodynamics,
 
 
Day 8 
168 hours after end of 
infusion ± 3 hours 
FPA150 PK (serum) 
FPA150 and/or pembrolizumab pharmacodynamics, 
 
FPA150 and/or pembrolizumab pharmacodynamics, 
 
FPA150 and/or pembrolizumab pharmacodynamics 
 
Day 15 
 
FPA150 PK (serum) (within ± 1 day) 

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Study Cycle 
Study Day 
Time Point 
Type of Sample 
Cycles 2, 3, 
4, 5, 7, 9 
Day 1 
Prior to infusion 
Tumor Biopsy  
(Cycle 3 only) 
FPA150 PK (serum) (≤ 4 hours prior to dosing)   
For pembrolizumab PK at Cycles 2, 3, and 7 only) 
FPA150 ADA (serum)  
(Cycles 2, 3,5, 9 only 
For pembrolizumab ADA at Cycles 2, 3, and 7 only) 
FPA150 and/or pembrolizumab pharmacodynamics, 
 
FPA150 and/or pembrolizumab pharmacodynamics, 
 
 
FPA150 and/or pembrolizumab pharmacodynamics, 
 
 
FPA150 and/or pembrolizumab pharmacodynamics 
 
 
FPA150 and/or pembrolizumab Tumor Markers (serum) 
15 minutes after end 
of infusion 
FPA150 PK (serum) (± 10 min) 
Every 4th 
dose 
(12 weeks) 
after Cycle 9  
Day 1 
Prior to infusion 
FPA150 PK (serum) (≤ 4 hours prior to dosing) 
FPA150 ADA (serum)  
(prior to dose for Cycles 13, 17 and every 8th dose 
[24 weeks] after Cycle 17) 
FPA150 and/or pembrolizumab Tumor Markers (serum) 
(cycles 13, 17, 21, and 25 only) 
End of 
Treatment 
Follow-up 
Period  
(28 [±7] days 
and 100 [±7] 
days post-last 
dose) 
Study 
discontinuation/ 
Progressive 
disease 
Post treatment 
FPA150 and/or pembrolizumab PK (serum) 
FPA150 and/or pembrolizumab ADA (serum) 
FPA150 pharmacodynamics, 
 
 
FPA150 and/or pembrolizumab pharmacodynamics, 
 
 
FPA150 and/or pembrolizumab pharmacodynamics, 
 
 
 
Abbreviations: ADA = anti-drug antibody; 
 
 PK = pharmacokinetics 
 
 
 
 

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APPENDIX 3:  
LIST OF POTENTIAL PHARMACODYNAMIC SAMPLES FOR 
ANALYSES 
Pharmacodynamic samples for analyses may include, but are not limited to, the following: 
• Tumor biopsy samples 
− Immunohistochemistry (IHC) analysis of selected biomarkers  
− 
 
• Blood samples 
− 
− 
− 
 
 

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APPENDIX 4:  
EASTERN COOPERATIVE ONCOLOGY GROUP PERFORMANCE 
STATUS 
Table 14: 
Eastern Cooperative Oncology Group Performance Status 
Grade 
 
Performance Status Criteria 
0 
 
Fully active, able to carry on all pre-disease activities without restriction. 
1 
 
Restricted in physically strenuous activity but ambulatory and able to carry out work 
of a light sedentary nature (light housework, office work). 
2 
 
Ambulatory and capable of all self-care but unable to carry out any work activities. 
Up and about more than 50% of waking hours. 
3 
 
Capable of only limited self-care, confined to bed or chair more than 50% of waking 
hours. 
4 
 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 
 
 
 

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APPENDIX 5:  
CLINICAL LABORATORY TESTS 
The laboratory parameters outlined in Table 15 will be determined in accordance with the 
Schedule of Assessments and will be performed locally. 
Table 15: 
Clinical Laboratory Tests 
Hematology: 
 
Complete blood cell (CBC) with differential: 
 
 
white blood cells (WBC) 
platelets  
 
ANC 
hemoglobin 
 
neutrophils (%) 
hematocrit 
 
eosinophils (%) 
red blood cells (RBC) 
 
basophils (%) 
 
lymphocytes (%) 
 
monocytes (%) 
Urinalysis: 
 
Dipstick (appearance, color, pH, specific gravity, ketones, protein, glucose, bilirubin, nitrite, urobilinogen, and 
occult blood) 
 
If dipstick is positive (2+ or greater) for blood or protein, perform a microscopic examination. 
Clinical chemistry: 
 
Albumin                                                                 
 
alkaline phosphatase 
glucose 
ALT (SGPT) 
lactate dehydrogenase (LDH) 
AST (SGOT) 
phosphate 
blood urea nitrogen (BUN) 
potassium 
calcium 
sodium 
chloride 
total bilirubin 
carbon dioxide (CO2 [bicarbonate]) 
total cholesterol 
creatinine 
total protein 
direct bilirubin  
uric acid  
magnesium 
Screening laboratory tests include: Serology for Hepatitis B (HBsAg and HBcAb), and Hepatitis C (HCV RNA) 
Serum pregnancy test: In women of childbearing potential only. 
Urine pregnancy test: In women of childbearing potential only. 
Coagulation: INR and APTT 
Abbreviations for Table 11 and for notes: ADA = anti-drug antibodies; ALT = alanine transaminase; ANC = 
absolute neutrophil count; APTT = activated partial thromboplastin time; AST = aspartate transaminase; 
BUN = blood urea nitrogen; CBC = complete blood count; GGT = gamma-glutamyltransferase; HBcAb = 
hepatitis B core antibody; HBsAg = hepatitis B virus surface antigen; HCV = hepatitis C virus; INR = international 
normalized ratio; LDH = lactate dehydrogenase; PK = pharmacokinetics; RBC = red blood cell; RNA = ribonucleic 
acid; WBC = white blood cells.  
Notes:  
 Local hematology and blood chemistry test results must be obtained within 96 hours of dosing to confirm 
eligibility.  
 If either AST or ALT is elevated, obtain total serum bilirubin and alkaline phosphatase; repeat daily or other 
interval, as clinically indicated, until resolved or stable.  
 Additional tests to rule out drug-induced liver injury (eg, abdominal ultrasound, serum GGT, hepatitis serology) 
may be obtained at any time, if clinically indicated.  

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 Samples for PK, ADA, and pharmacodynamic analyses will be assessed at a central laboratory. Tumor markers  
will be assessed at a central laboratory. All other (safety) laboratory tests will be assessed locally.  

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APPENDIX 6:  
NEW YORK HEART ASSOCIATION CLASSIFICATION 
Table 16: 
New York Heart Association Classification 
Class I 
Subjects with no limitation of activities; they suffer no symptoms from ordinary activities. 
Class II 
Subjects with slight, mild limitation of activity; they are comfortable with rest or with 
mild exertion. 
Class III 
Subjects with marked limitation of activity; they are comfortable only at rest. 
Class IV 
Subjects who should be at complete rest, confined to bed or chair; any physical activity 
brings on discomfort and symptoms occur at rest. 
 
 
 

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APPENDIX 7:  
PROTOCOL AMENDMENT HISTORY 
Document 
Date 
Amendment 2 
04 February 2019 
Amendment 1 
23 January 2018 
Original Protocol 
31 October 2017 
 
 
 

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AMENDMENT 2 (05 FEBRUARY 2019) 
Overall Rationale for the Amendment: 
The protocol was updated to include language for FPA150 in combination with pembrolizumab 
cohorts and to incorporate additional updates and clarifications to study procedures that have 
been identified.  These changes are summarized below. Additional changes were made to correct 
formatting and typographical errors.  
Table 17: 
Document History 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1 Protocol 
Synopsis, Objectives and 
Endpoints and Section; 
Table 2 
• Included language to incorporate for 
FPA150 in combination with 
pembrolizumab and to clarify 
existing objectives or endpoints for 
FPA150 monotherapy. 
• Objectives and Endpoints for Safety, 
Pharmacokinetic, Immunogenicity, 
Efficacy, Exploratory 
Pharmacokinetics, Exploratory 
Immunogenicity, and Exploratory 
Pharmacodynamic Biomarkers for 
Phase 1a and Phase 1b have been 
changed to further clarify for 
monotherapy cohorts and to include 
for combination cohorts 
 
• Abbreviations from below the table 
have been removed to avoid 
duplication of definitions  
• Removed abbreviations 
Section 1 Protocol 
Synopsis, Investigational 
Product; Section 6.1 
Treatments Administered 
• To provide details of 
pembrolizumab formulation and 
dosing for combination cohorts 
• To provide details of any updates to 
FPA150 investigational product 
• Addition of pembrolizumab 
investigational product description 
and dosing 
• Addition of larger FPA150 
investigational product vial size 
Section 1 Protocol 
Synopsis, Study Design; 
Section 4 Study Design 
• Added clarified language and tables 
for the FPA150 in combination with 
pembrolizumab cohorts. 
• Addition of combination cohorts  
 
• Clarified language around what the 
requirements are for archival tumor 
tissue and/or fresh biopsies for the 
FPA150 monotherapy cohorts and 
for the FPA150 in combination with 
pembrolizumab cohorts 
• Clarification of requirements for 
archival tumor tissue and fresh 
biopsies for all cohorts 
 
• Clarified the naming conventions for 
each of the monotherapy and 
combination cohorts and removed 
the Phase 1b monotherapy urothelial 
cohort 
• Addition of monotherapy dose 
exploration cohort 

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Section # and Name 
Description of Change 
Brief Rationale 
 
• Added cohort specific details for 
additional FPA150 monotherapy 
dose exploration cohort and FPA150 
in combination with pembrolizumab 
cohorts 
• Clarification of monotherapy 
treatment cohorts  
 
• Updated the number of patients and 
the sample size based on the 
addition of the combination cohorts 
• Update the number of patients and 
sample size 
Section 1 Protocol 
Synopsis, Eligibility 
Criteria; Section 5.1 
Inclusion Criteria; 5.2 
Eligibility Criteria 
• Specified that inclusion criteria will 
be applicable for both monotherapy 
and combination therapy for 
phase 1a and phase 1b 
• Inclusion criteria have been clarified 
 
• Added language to further clarify 
the inclusion criteria for phase 1b 
monotherapy breast cancer to 
include specifics for triple negative 
breast and HR+  
• Inclusion criteria for disease specific 
cohorts have been added 
 
• Added inclusion criteria for the 
phase 1b FPA150 in combination 
with pembrolizumab ovarian cohort 
• Additional Inclusion criteria have 
been added.  
 
• Added exclusion criteria 
• Additional Exclusion Criteria have 
been added 
Section 1 Protocol 
Synopsis, Statistical 
Methods; Section 9.1 
Sample Size 
Determination 
• Patient numbers were revised to 
align with the additional number of 
patients enrolling in the 4 lower 
dose cohorts 
• Sample size determination has been 
changed. 
Section 1 Protocol 
Synopsis, Safety Analysis 
• Added clarified language that this 
study includes both monotherapy 
and combination therapy 
• Clarification of cohorts has been 
added 
Section 1 Protocol 
Synopsis, Efficacy 
Analysis 
• Added language for Simon’s 2-stage 
design 
• Clarification of criteria for closing 
cohorts with limited activity 
Section 1 Protocol 
Synopsis, Pharmacokinetic 
Analysis; Section 8.8 
Pharmacokinetics; Section 
9.4.3 Pharmacokinetic 
Analyses 
• Added language about what will 
happen to the pembrolizumab PK 
samples for patients enrolled into 
the FPA150 in combination cohorts.   
• Addition of analysis for combination 
samples 
List of Abbreviations 
• New terms were added as a result of 
the combination cohorts  
• Rearranged terms so that all are in 
alphabetical order 
• Clarification of list of abbreviations 
• Addition of new terms from new 
text 
• Moved terms so that they are 
alphabetical 
• Removed terms that are not in the 
protocol 

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Section # and Name 
Description of Change 
Brief Rationale 
Section 2.1 Study 
Rationale 
• Added language to support the 
combination cohorts 
• Removed urothelial as one of the 
Phase 1b monotherapy cohorts  
• Addition of Combination 
 
• Removed one of the Phase 1b 
monotherapy cohorts 
Section 2.2.5 Clinical 
Experience with FPA150 
• Added limited safety data from our 
completed cohorts in Phase 1a 
FPA150 monotherapy to support the 
MTD/RD of FPA150 
• Addition of safety data from 
Phase 1a 
Section 2.2.6 
Pembrolizumab 
Background 
• Added background information on 
Pembrolizumab for the combination 
cohorts 
• Added Pembrolizumab language 
Section 2.2.7 Rationale for 
Combination with 
Pembrolizumab 
• Added language from research to 
support the addition of the 
pembrolizumab combination with 
FPA150 cohorts 
• Added Pembrolizumab combination 
rationale  
Section 2.3 Benefit/Risk 
Assessment 
• Added supporting language 
regarding safety from Phase 1a 
Monotherapy Dose Escalation 
• Additional monitoring of patients 
after first infusion of FPA150 
• Clarified that additional guidance on 
FPA150 dosing is located in other 
study documents 
• Clarified duration of post first 
infusion monitoring window of 
patients. 
Section 4 Study Design; 
Figure 4 
• Added updated study schema for 
monotherapy cohorts  
• Added updated study schema for 
combination cohorts 
• Updated schema based on completed 
cohorts 
• Added new schema 
Section 1 Protocol 
Synopsis; Section 4.1.2.2 
Definition of a Dose-
Limiting Toxicity 
• Added language and tables to 
specifically define Dose Limiting 
Toxicities for monotherapy and 
combination cohorts.   
• Added to include pembrolizumab  
Section 4.5 Scientific 
Rationale for Study Design 
• Added language that defines when 
to initiate the combination cohorts 
based on emerging data from the 
ongoing phase 1a monotherapy 
cohorts and from preclinical studies 
• Clarified timing to initiate the 
FPA150 in combination with 
pembrolizumab cohorts 
Section 4.6 Justification 
for Dose and Dosing 
Regimen 
• Clarified language for the starting 
dose and dosing regimen of FPA150 
Phase 1a Dose Escalation cohorts 
• Added language for the proposed 
dose of pembrolizumab 
• Added rationale to how the starting 
dose was defined 
 
• To provide guidance for 
pembrolizumab 
Section 4.7 Patient 
Selection 
• Added language to include the 
combination cohorts and edited 
existing language to clarify the 
patient selection 
• Added to include pembrolizumab 

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Section # and Name 
Description of Change 
Brief Rationale 
Section 6.3.2 Table 10 
Study Treatment Regimen 
of Combined Treatment of 
FPA150 and 
Pembrolizumab 
• Addition of a table to show the 
treatment regimen for combination 
therapy 
• Added to clarify the treatment for 
pembrolizumab combination cohorts 
Section 6.4 Dose 
Modifications 
• Added dose modification language 
and criteria for the combination 
cohorts.  
• Added language regarding Dose 
Escalations if there is radiographic 
response  
• Added to include for pembrolizumab 
combination cohorts 
• Added clarification for escalation 
within a cohort 
Section 6.5 Maximum 
Duration of Treatment 
• Added language to define the 
maximum number of doses and/or 
duration of treatment for FPA150 
and pembrolizumab 
• Added language to specify actions to 
take in combination cohorts if one of 
the two drugs has been discontinued; 
the patient may continue to receive 
the other drug as monotherapy 
• Clarified how long a patient on 
FPA150 monotherapy or 
pembrolizumab can be on treatment 
 
• Clarified that monotherapy 
treatment can continue if one of the 
drugs in the combination therapy is 
stopped.  
Section 6.8 Study Drug 
Accountability 
• Added language to specify that 
accountability will be performed for 
FPA150 and/or pembrolizumab 
• Clarified that drug accountability 
applies to both FPA150 and 
pembrolizumab 
Section 6.9 Treatment 
Compliance 
• Added language to include 
pembrolizumab to treatment 
compliance 
• Clarified that treatment compliance 
applies to both FPA150 and 
pembrolizumab 
Section 6.10 Concomitant 
Therapy 
• Added language for pembrolizumab 
stating that the guidance from the 
package insert should be followed 
• Clarified that the package insert for 
pembrolizumab should be followed 
Section 7.1 
Discontinuation of Study 
Treatment 
• Added language that pembrolizumab 
treatment can continue up to 
24 months 
• Patients can only be on 
pembrolizumab for 24 months 
Section 8.1.1 Informed 
Consent Requirements by 
Study Phase 
• Clarified and simplified ICF 
requirement language for all 
monotherapy and combination 
therapy cohorts  
• Clarified that sites should be having 
subjects sign the most recent 
approved ICFs 
Section 8.4 Tumor Tissue 
• Added clarification of what the 
requirements are regarding archival 
tissue or tumor tissue for all 
monotherapy and combination 
therapy cohorts 
• Added updated the number of 
patients who will require a fresh 
biopsy at screening and prior to 
Cycle 3 Day 1. 
• Added clarified language of when 
the biopsy may be done for the 
• Clarified what and when archival 
and fresh biopsies are required for 
each cohort 
 
 
• Clarified the subset of patients that 
will require a fresh biopsy at 
screening 
 

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Section # and Name 
Description of Change 
Brief Rationale 
sample required prior to Cycle 3 
Day 1 
• Clarified when the biopsy for 
Cycle 3 Day 1 should be collected 
Section 8.6 Efficacy 
Assessments 
• Added language stating the first on 
study imaging assessment should be 
performed within 28 Days of 
Cycle 1 Day 1  
• Changed the frequency of tumor 
scans to every 6 weeks for the first 
6 months and then every 12 weeks 
• Clarified when tumor assessment 
scan needs to occur  
 
 
• Clarified the scan frequency for 
tumor assessments to shorten the 
duration to determine patient tumor 
status earlier 
Section 8.7.2 Pregnancy 
on Study 
• Added language to reference the 
pembrolizumab USPI 
• Clarifying to ensure sites remember 
to refer to the pembrolizumab 
package insert 
Section 8.10 
Immunogenicity 
Assessments 
• Added immunogenicity language for 
pembrolizumab  
• Clarifying that immunogenicity for 
pembrolizumab is also included 
Section 8.12.5 Treatment 
of Overdose 
• Added language regarding overdose 
while on treatment with 
pembrolizumab 
• Clarifying overdose for 
pembrolizumab 
Section 8.14 End of 
Treatment Follow-Up 
• Added language to clarify that this is 
for both monotherapy and 
combination therapy 
• Added language for overdose of 
pembrolizumab 
• Clarification of cohorts 
 
 
• Clarified addition of pembrolizumab 
for overdoses 
Appendix 1: Schedule of 
Assessments 
• Clarified that Schedule of 
Assessments is applicable to both 
monotherapy and combination 
therapy 
• Added clarification of applicable 
cohorts 
 
• Removed superscript from 
“subsequent cycles” 
• Corrected transcription error 
 
• Clarified EOT 28 Days and EOT 
100 Days by adding an additional 
column and having each visit have 
their own column. 
• Clarified study procedures 
 
• Added HBcAb to Hepatitis B testing 
• Clarified study procedures 
 
• Clarified that for tumor markers 
sites should refer to Appendix 2 for 
additional information and specific 
sampling times 
• Clarified study procedures 
 
• Clarified that adverse events and 
concomitant medication should only 
be followed up until EOT 28 Days 
• Clarified study procedures 
 
• Added a row for thyroid function 
testing 
• Clarified study procedures 
 
• Added time windows for footnote e 
• Clarified study procedures 

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Section # and Name 
Description of Change 
Brief Rationale 
 
• Clarified that ECGs should be down 
before PK draws in footnote f 
• Clarified study procedures 
 
• Added language to clarify cohort 
names for monotherapy and 
combination therapy in footnote h 
• Clarified study procedure 
 
• Clarified which monotherapy and 
combination therapy cohorts will 
require B7-H4 expression results in 
footnote i 
• Clarified study procedures 
 
• Updated CT/MRI collection 
frequency from 9 weeks to 6 weeks 
in footnote k 
• Clarified study procedures 
 
• Updated the schedule of tumor 
marker collection in footnote l 
• Clarified study procedures 
 
• Added clarified language for PK 
collection requirements for 
monotherapy and combination 
therapy in footnote n 
• Clarified study procedures 
 
• Added dosing guidance for 
pembrolizumab in footnote o 
• Clarified study procedures 
 
• Clarified requirements for footnote p 
• Clarified study procedures 
 
• Added footnote q regarding when to 
complete screening assessments 
• Clarified study procedures 
 
• Added footnote r for thyroid testing 
• Clarified study procedures 
 
• Added footnote s to clarify that 
adverse events and concomitant 
medication should be followed 
through EOT 28 Days 
• Clarified study procedures 
Appendix 2: Schedule of 
pharmacokinetic, 
immunogenicity, and 
pharmacodynamic blood 
sample collection; Table 9 
• Added language to include 
pembrolizumab to all impacted 
samples 
•  
• Addition of pembrolizumab 
 
• Added pembrolizumab PK and ADA 
samples to be collected only at 
Cycles 1, 2, 3, and 7 prior to 
infusion and 15 min post infusion.  
• Clarified study procedures 
 
• Added pembrolizumab ADA 
samples to be collected only at 
• Clarified study procedures 
 
• Cycles 1, 2, and 3 prior to infusion 
and 15 min post infusion.  
• Clarified study procedures 
 
• Clarified requirements for 
pharmacodynamics samples on 
Cycle 1 Day 4 
• Clarified study procedures 
 
• Clarified requirement for 
 
 on Cycle 1 Day 8 
• Clarified study procedures 

FPA150-001 Clinical Protocol 
Amendment 2 
04 February 2019 
Five Prime Therapeutics, Inc. 
Page 131 of 131  
Confidential 
Section # and Name 
Description of Change 
Brief Rationale 
 
• Clarified Tumor biopsy is required 
only at Cycle 3 
• Clarified study procedures 
 
• Clarified requirement 
 
at Cycle 2, 3, 4, 5, 7, and 9 
• Clarified study procedures 
 
• Added language 
 at 
Cycle 3 
• Clarified study procedures 
 
• Clarified that tumor markers are 
required at Cycles 2, 3, 4, 5, 7, and 9 
• Clarified study procedures 
 
• Added windows for PK collection 
• Clarified study procedures 
 
• Clarified tumor markers 
requirements after cycle 9 
• Clarified study procedures 
 
• Clarified tumor biopsy requirement 
at EOT 28 Days 
• Clarified study procedures 
 
• Added language 
 at 
EOT 28 Days 
• Clarified study procedures 
Appendix 3: List of 
Potential 
Pharmacodynamic samples 
for analyses 
• Added clarification that the list 
provided is only a sample of what 
analyses may be included but it is 
not limited to only those 
• Clarified study procedures 
 
• 
 
• Clarified study procedures 
Appendix 5: Clinical 
laboratory tests 
• Clarified what the required clinical 
chemistries are 
• Clarified study procedures 
 
• Added additional abbreviations 
• Clarified study procedures 
 
• Clarified what sample analysis will 
be completed at central laboratory 
• Clarified study procedures 
 

FPA150-001 Clinical Protocol 
Amendment 1 
23 January 2018 
Five Prime Therapeutics, Inc. 
Page 104 of 108  
Confidential 
AMENDMENT 1 (23 JANUARY 2018) 
Overall Rationale for the Amendment: 
The protocol was updated to clarify the patient population and study procedures. These changes 
are summarized below. Additional changes were made to correct formatting and typographical 
errors.  
Table 13: 
Document History 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1 Protocol 
Synopsis, 
Section 5.1.1 Phase 1a 
Inclusion Criteria, and 
Section 5.1.3 
Additional Cohort-
Specific Inclusion 
Criteria for Phase 1b 
• Inclusion Criteria #4 has been 
changed to patients should be 
refractory to or intolerant of 
existing therapy(ies) known to 
provide clinical benefit for 
their condition. 
• Inclusion #15 has been 
changed to clarify Hepatic 
safety labs must meet the 
following criteria: AST and 
ALT ≤ 3× ULN (AST and 
ALT < 5× ULN in patients 
with liver metastases is 
permitted) 
• Additional Inclusion Criteria 
for Cohort 1b1 Breast 
Carcinoma patients to include 
HER2 negative disease. 
• Clarification of Cohort 1b2 
Ovarian Carcinoma Inclusion 
Criteria to include diagnosis 
that is refractory to existing 
therapy(ies) known to provide 
clinical benefit. 
• All criteria have been 
sequentially numbered. 
• Eligibility criteria changed to 
clarify prior treatment 
requirements 
 
 
 
• Allow a higher cut-off for 
liver enzyme elevations in 
patients with liver metastases 
which are likely to be 
common in the solid tumor 
population being evaluated in 
this study 
 
• Eligibility criteria changed to 
include only patients with 
HER2 negative breast cancer 
 
• Eligibility criteria changed to 
clarify prior treatment 
requirements 
 
 
 
• For data management 
purposes  

FPA150-001 Clinical Protocol 
Amendment 1 
23 January 2018 
Five Prime Therapeutics, Inc. 
Page 105 of 108  
Confidential 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1 Protocol 
Synopsis and Section 
5.2 Exclusion Criteria 
Phase 1a and Phase 1b 
• Clarified that inhaled, 
intranasal, intraocular, and 
joint injections of steroids are 
exceptions to exclusion 
criteria #1 
• Specfied the components of 
the investigational drug 
product formulation in 
exclusion criteria #6 
• Specification of the types of 
steroid formulations allowable 
on study 
• To provide formulation details 
within exclusion criterion for 
criterion 
Section 1 Protocol 
Synopsis, Section 4.1 
Overall Design, and 
Section 4.1.2 Study 
Design: Phase 1a 
Dose Escalation 
• Addition of lower dose initial 
accelerated titration design 
• Phase 1a Dose Escalation 
design was revised to include 
4 additional lower dose 
cohorts (0.01, 0.03, 0.1, and 
0.3 mg/kg) to collect 
additional safety data 
Section 1 Protocol 
Synopsis and Section 
4.1.2.2 Dose-Limiting 
Toxicity Evaluation 
and Dose Escalation 
•  Language explaining the 
accelerated dose escalation 
titration design for additional 
4 lower dose cohorts  
• 4 additional lower dose 
cohorts (0.01, 0.03, 0.1, and 
0.3 mg/kg) have been added at 
an accelerated titration design 
has been added to collect 
additional safety data at lower 
doses 
Section 1 Protocol 
Synopsis, Section 4.3 
Number of Patients, 
and Section 9.1 
Sample Size 
Determination 
• Updated number of patients  
• Patient numbers were revised 
to align with the additional 
number of patients enrolling 
in the 4 lower dose cohorts 
Section 4.1.2.1 
Definition of a Dose-
Limiting Toxicity 
• Revised DLT definition to 
include adverse events 
regardless of attribution 
(except for those events 
clearly due to the underlying 
disease or extraneous causes) 
and included Grade 4 
neutropenia that lasts more 
than 7 days. 
• DLT criteria were revised to 
clarify the adverse events that 
should be considered for DLT 
determinations 
Section 4.2.2 Phase 1a 
Dose Exploration 
• Clarified that fresh biopsies 
are acceptable in the instance 
that archival tumor tissue is 
not available. 
• Clarified that fresh or archival 
tumor tissue is acceptable  

FPA150-001 Clinical Protocol 
Amendment 1 
23 January 2018 
Five Prime Therapeutics, Inc. 
Page 106 of 108  
Confidential 
Section # and Name 
Description of Change 
Brief Rationale 
Section 4.2.3 Phase 1b 
Dose Expansion 
• Clarified that fresh biopsies 
are acceptable in the instance 
that archival tumor tissue is 
not available. 
• Clarified that fresh or archival 
tumor tissue is acceptable 
Section 4.7 
Justification for Dose 
and Dosing Regimen 
• Correction of the safe starting 
dose in humans and the upper 
value of Cmax 
• Added “cells” after CT26  
• Corrected transcription error 
 
 
• To clarifiy details of 
experimental model used 
Section 6.1.3 FPA150 
Administration 
• Additional guidance for 
available dosing instructions 
 
 
• Additional monitoring of 
patients after first infusion of 
FPA150 
• Clarified that additional 
guidance on FPA150 dosing is 
located in other study 
documents 
• Clarified duration of post first 
infusion monitoring window 
of patients. 
Section 6.2.2 Dose 
Escalation within a 
Cohort 
• Addition of intrapatient dose 
escalation  
• Clarified that intrapatient dose 
escalation will be permitted 
for patients in dose cohorts up 
to 1mg/kg 
Section 6.2.3 Toxicity 
at Lowest Dose Level 
• Clarified first dose level  
 
 
• Clarified dose reduction  
• Clarification of the lowest 
dose level to align with the 
new lowest dose level. 
• Clarification that the dose can 
be reduced from 0.1 mg/kg 
down to 0.005 mg/kg  
Section 6.7 
Concomitant Therapy 
• Addition of bisphosphonates 
and denosumab as permitted 
concomitant medications 
• Clarified that bisphosphonates 
and denosumab are permitted 
supportive care medications 
on study 
Section 7.4 Premature 
Termination of the 
Study 
• Added section for early 
stopping rules in cases of 
excessive toxicity or deaths.  
• Clarified reasons for which 
the Sponsor could terminate 
the study early 

FPA150-001 Clinical Protocol 
Amendment 1 
23 January 2018 
Five Prime Therapeutics, Inc. 
Page 107 of 108  
Confidential 
Section # and Name 
Description of Change 
Brief Rationale 
Section 8.12.2 
Adverse Event 
Definitions 
• Clarified language that 
Disease Progression is not an 
AE or SAE and that 
concurrent signs and 
symptoms clearly associated 
with disease progression itself 
should not be reported as an 
AE or SAE 
• Clarification of reporting 
requirements for signs and 
symptoms of Disease 
Progression 
Section 10 Ethical, 
Legal, and 
Administrative 
Aspects 
• Added section with standard 
legal and regulatory content 
• Section was added to adhere 
to ICH E6 requirements 
Appendix 1 Schedule 
of Assessments 
• Added visit windows to 
Cycle 1, Cycle 2 and 
Subsequent Cycles 
• Clarified language in 
footnote h that the biopsy 
should be taken at the EOT 
day 28 visit 
• Removed screening from 
footnote l to clarify that tumor 
markers should only be done 
at Day 1 of each every cycle 
• Clarified that serum 
pregnancy test can also be 
performed in footnote m  
• Added B7-H4 to Screening 
visit 
• Clarified visit for Tumor 
Markers 
 
• Clarified language in 
footnote e that patients should 
be monitored post dose 
• Standard visit windows were 
previously missing for some 
visits 
• Clarification of study 
procedures 
 
• Clarification of study 
procedures 
 
 
• Clarification of study 
procedures 
 
• Clarification of study 
procedures 
• Clarification of study 
procedures 
• Clarification of study 
procedures 

FPA150-001 Clinical Protocol 
Amendment 1 
23 January 2018 
Five Prime Therapeutics, Inc. 
Page 108 of 108  
Confidential 
Section # and Name 
Description of Change 
Brief Rationale 
Appendix 2 Schedule 
of pharmacokinetic, 
immunogenicity, and 
pharmacodynamic 
blood sample 
collection 
• Clarified language regarding 
sample collection to mimic 
what is listed in the body of 
the protocol. 
• Added sample collection 
window  
• Clarification of study 
procedures 
 
 
• Standard sample collection 
windows were previously 
missing for some timepoints