A Phase 1a/1b Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers
Phase: PHASE1
Conditions: Advanced Solid Tumors, Head and Neck Cancer, Pancreatic Cancer, Ovarian Cancer, Renal Cell Carcinoma, Malignant Glioma, Non-small Cell Lung Cancer
Sponsor: Five Prime Therapeutics, Inc.

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A Phase 1a/1b Study of Cabiralizumab in Combination with 
Nivolumab in Patients with Selected Advanced Cancers 
Protocol Number: 
FPA008-003 
Investigational Products: 
Cabiralizumab (FPA008) and Nivolumab 
IND Number: 
126401 
Development Phase: 
Phase 1a/1b 
Indications Studied: 
Advanced Cancers 
Protocol Version: 
5 – Amendment 4 
Date of Protocol: 
7 June 2017 
Supersedes:  
Version 4, Protocol Amendment 3  
dated 15 April 2016 
Sponsor: 
Five Prime Therapeutics, Inc. 
 
  
Responsible Medical Officer: 
Sandeep Inamdar, MBBS 
 
  
Confidential 
This document contains proprietary and confidential information of Five Prime Therapeutics, Inc. (FivePrime) and may not be reproduced or 
disclosed in whole or in part without written authorization from Five Prime Therapeutics, Inc. 

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Protocol Synopsis 
Title: 
A Phase 1a/1b Study of Cabiralizumab in Combination with Nivolumab 
in Patients with Selected Advanced Cancers 
Protocol Number: 
FPA008-003 
Clinical Phase: 
1a/1b 
Sponsor: 
Five Prime Therapeutics, Inc. 
Study Centers: 
There will be approximately 50 study centers participating in this study. 
Objectives: 
 
Phase 1a Objectives 
 
Primary 
• To assess the safety and tolerability of cabiralizumab as monotherapy 
• To assess the safety and tolerability of cabiralizumab in combination with 
nivolumab  
• To determine the recommended dose (RD) of cabiralizumab in combination 
with a fixed dose of nivolumab  
Secondary 
• To characterize the PK profile of cabiralizumab  
• To characterize the PK profile of nivolumab when administered in 
combination with cabiralizumab 
• To characterize the immunogenicity of cabiralizumab and nivolumab  
• To characterize the PD profile of cabiralizumab and nivolumab by analyses 
of biopsies (including IHC analyses of CD8, CD68, and other selected 
biomarkers)  
 
 
 
 
Phase 1b Objectives 
 
Primary 
• To evaluate the clinical benefit of cabiralizumab in combination with 
nivolumab in patients with selected advanced cancers through the analysis 
of objective response rate (ORR) 
• To evaluate the safety and tolerability of cabiralizumab in combination with 
nivolumab in patients with selected advanced cancers treated at the RD  

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Phase 1b Objectives 
(Cont.) 
  
Secondary 
• To evaluate the clinical benefit of cabiralizumab in combination with 
nivolumab in patients with selected advanced cancers through the analysis 
of overall survival (OS), duration of response (DOR), and progression free 
survival (PFS) 
• To characterize the PK profile of cabiralizumab when administered in 
combination with nivolumab 
• To characterize the PK profile of nivolumab when administered in 
combination with cabiralizumab 
 
• To characterize the immunogenicity of cabiralizumab and nivolumab  
• To characterize the PD profile of cabiralizumab and nivolumab by analyses 
of biopsies (including IHC analyses of CD8, CD68, and other selected 
biomarkers)  
• To assess the association of selected biomarker measures and clinical 
efficacy measures using pre-treatment and on-treatment tumor biopsies 
 
 
 
Investigational 
Products 
Cabiralizumab Solution for Intravenous Infusion 
Nivolumab Solution for Intravenous Infusion 
Study Design 
This study is a Phase 1a and 1b, open-label, multicenter, dose escalation and 
dose expansion study to evaluate the efficacy, safety, tolerability, PK, and PD 
of cabiralizumab as monotherapy and in combination with nivolumab in 
patients with selected advanced cancers. Cabiralizumab is a humanized 
monoclonal antibody directed against CSF1R and nivolumab is a fully human 
monoclonal antibody directed against PD-1. For the combination arms of the 
study (except for the 3-week dosing regimen cohort -Cohort 1aD), 
cabiralizumab and nivolumab will be given on Day 1 of each 14-day treatment 
cycle. For cohort 1aD, cabiralizumab and nivolumab will be administered on 
Day 1 of each 21-day treatment cycle. Nivolumab will be administered as an 
IV infusion over 30 minutes followed by a 30- to 60-minute rest, and then 
cabiralizumab will be administered as an IV infusion over 30 minutes. 
The study includes Phase 1a and Phase 1b. Patients will be enrolled into either 
Phase 1a or Phase 1b of the study. 
Phase 1a consists of 7 dose escalation cohorts, one 3-week dosing regimen 
cohort. Phase 1a may also include up to 40 additional patients that will be 
enrolled for further exploration of safety and PK. 
Phase 1b consists of 7 tumor-specific expansion cohorts across 6 cancer types.  

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Study Design 
(Cont.) 
  
Phase 1a: Dose 
Escalation 
In Phase 1a, a modified 3 + 3 + 3 design will be used to assess the safety of 
cabiralizumab in monotherapy and  in combination with nivolumab.  
Dose escalation will be based on the number of DLTs experienced during the 
DLT evaluation interval as determined by the Investigators and Medical 
Monitor (see Section 3.1.2.1.1 for DLT criteria). The DLT evaluation interval 
begins on the first day of treatment and continues for 28 days. Patients who 
receive at least 2 doses of study drug during the 28-day evaluation interval or 
patients who discontinue study treatment for drug-related AEs before receiving 
2 doses of study drug will be considered evaluable for DLT determination. In 
consultation with Investigators, the Sponsor has the option to investigate dose 
levels different than those defined in the protocol. 
 
Dose escalation in Phase 1a proceeds as follows: 
• 
If none of the first 3 evaluable patients in a dose cohort experiences a DLT 
within the DLT evaluation interval, then the next 3 patients will be treated 
at the next higher dose cohort.  
• 
If 1 of the first 3 evaluable patients in a cohort experiences a DLT within 
the DLT evaluation interval, then 3 additional patients will be treated in 
that dose cohort.  
− 
If no more than 1 of the first 6 evaluable patients experiences a DLT 
during the DLT evaluation interval, then the next 3 patients will be 
enrolled at the next higher dose cohort.  
− 
If 2 of the first 6 evaluable patients in a cohort experience a DLT, that 
cohort will be expanded to 9 evaluable patients.  
• 
If 2 of the first 3 evaluable patients experience a DLT within the DLT 
evaluation interval, then 6 additional patients may be treated in that dose 
cohort, upon approval of Investigators and the Medical Monitor.  
• 
If the incidence of DLT is > 33% in the overall population up to 9 patients, 
that dose level has exceeded the MTD and dose escalation will be 
terminated.  

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Study Design  
(cont.) 
 
Phase 1a: 3-Week 
Dosing Regimen 
An alternative dosing regimen cohort (1aD) with 10 patients has been added to 
characterize the PK and safety of cabiralizumab in combination with 
nivolumab when administered at a 3-week dosing schedule. In this cohort, 4 
mg/kg cabiralizumab in combination with 3 mg/kg nivolumab will be 
administered intravenously every three weeks until disease progression, 
unacceptable toxicity, or other reason for treatment discontinuation. Patients 
who enter this cohort will follow eligibility criteria for Phase 1a. Patients will 
not be evaluated for DLT as the dose frequency is less than Cohort 1aC3 
which has cleared the DLT window at the time of this amendment. 
Phase 1a: 
Exploration Cohort 
Based on emerging clinical and translational data, up to 40 patients will be 
included in Phase 1aE to further explore safety, PK, and PD at alternative dose 
levels or dosing schedules which have already successfully cleared their 
respective DLT periods. In each cohort, cabiralizumab either as monotherapy 
or in combination with nivolumab will be administered until disease 
progression, unacceptable toxicity, or other reason for treatment 
discontinuation. Patients who enter Phase 1aE will follow eligibility criteria for 
Phase 1a. 
Phase 1b: Dose 
Expansion 
 
Seven cohorts consisting of approximately 30 patients each in specific tumor 
types will characterize the safety and evaluate the efficacy at the RD of 
cabiralizumab in combination with nivolumab. In each cohort, 4 mg/kg 
cabiralizumab in combination with 3 mg/kg nivolumab will be administered 
intravenously every 2 weeks until disease progression, unacceptable toxicity, 
or other reason for treatment discontinuation. 
 
Notable Aspects of Study Conduct: 
Study History 
• Cohort 1aM1 (2 mg/kg cabiralizumab monotherapy) was enrolled first, 
followed by enrollment of a cohort of 3 new patients in the 1 mg/kg 
cabiralizumab and nivolumab combination cohort (1aC1).  
• Cohort 1aM2 (6 mg/kg cabiralizumab monotherapy) was opened after the 
DLT period cleared in the 2 mg/kg cabiralizumab monotherapy cohort 
(1aM1). 
• Cohort 1aM3 (4 mg/kg cabiralizumab monotherapy) was opened after DLTs 
were observed in Cohort 1aM2. 
• Cohort 1aM2 (6 mg/kg cabiralizumab monotherapy) was re-opened after the 
DLT period cleared in the 1aM3 (4 mg/kg cabiralizumab monotherapy) 
cohort (See Section 1.4 for the rationale for re-opening Cohort 1aM2) 
 

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Study Design  
(cont.) 
 
Phase 1b: Dose 
Expansion (cont.) 
• Cohort 1aC2 (2 mg/kg cabiralizumab and nivolumab combination) was 
opened after the DLT period cleared in the 1 mg/kg cabiralizumab and 
nivolumab combination cohort and 2 mg/kg cabiralizumab monotherapy 
cohorts (1aC1 and 1aM1, respectively).  
• Cohort 1aC3 (4 mg/kg cabiralizumab and nivolumab combination) was 
opened after the DLT period cleared in the 1 mg/kg and 2 mg/kg 
cabiralizumab and nivolumab combination cohorts (1aC1 and 1aC2 
respectively) and in the respective monotherapy cohorts. 
 
Study Plan 
• At least 3 patients will be enrolled into each dose escalation cohort.  
• Upon completion of the DLT period, approximately 40 additional patients 
may be enrolled in Phase 1aE to further characterize safety, PK, and PD. 
• Alternative dose levels of cabiralizumab may be tested based on safety, PK 
and biomarker data. 
• Patients in the combination cohorts can be treated beyond disease 
progression in accordance with protocol specific guidelines  
(see Section 4.3.8). 
• Tumor biopsies will be performed in at least 10 patients in each Phase 1b 
dose expansion cohort (optional for cohort 1b7 GBM) before treatment, at 1 
month post-treatment 
• Skin biopsies will be performed in all Phase 1a patients before treatment, at 
1 month post-treatment.  
• Post-disease response and/or progression tumor biopsy and skin biopsy will 
be optional for all patients. 
 
Dosing and Cohorts 
For patients in the monotherapy cohorts, cabiralizumab infusion will be 
administered as a 30-minute IV infusion on Day 1 of each 14-day treatment 
cycle. Patients in combination therapy cohorts will receive nivolumab infusion 
first at a dose of 3 mg/kg as a 30-minute IV infusion, with a 30 to 60-minute 
rest, followed by 30-minute IV infusion of cabiralizumab, on Day 1 of each 
treatment 14-day cycle. Patients in 3-week dosing regimen cohort (1aD) will 
receive the nivolumab and cabiralizumab infusion on Day 1 of each 21-day 
treatment cycle.  
If any Grade 3 or higher infusion reaction is observed during the proposed 
infusion rate of nivolumab 3 mg/kg over 30 minutes, the infusion rate will be 
extended to 60 minutes for all current and subsequent patients for the duration 
of this study.  

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Dosing and Cohorts 
(cont.) 
Phase 1aM: Monotherapy Dose Escalation Cohorts 
Cabiralizumab monotherapy in patients with advanced solid tumors 
• Cohort 1aM1: cabiralizumab 2 mg/kg every 2 weeks 
• Cohort 1aM2: cabiralizumab 6 mg/kg every 2 weeks 
• Cohort 1aM3: cabiralizumab 4 mg/kg every 2 weeks 
 
Phase 1aC: Combination Dose Escalation Cohorts 
Cabiralizumab and nivolumab combination therapy in patients with advanced 
solid tumors  
• Cohort 1aC1: cabiralizumab 1 mg/kg + nivolumab 3 mg/kg every 2 weeks 
• Cohort 1aC2: cabiralizumab 2 mg/kg + nivolumab 3 mg/kg every 2 weeks  
• Cohort 1aC3: cabiralizumab 4 mg/kg + nivolumab 3 mg/kg every 2 weeks 
• Cohort 1aC4: cabiralizumab 6 mg/kg + nivolumab 3 mg/kg every 2 weeks  
Alternative dose levels of cabiralizumab may be tested based on safety, PK 
and biomarker data. See Section 1.4 for cohort design and rationale. 
Phase 1aD: Combination 3-week Dosing Regimen Cohort 
Cabiralizumab and nivolumab combination therapy in patients with advanced 
solid tumors  
Cohort 1aD1: cabiralizumab 4 mg/kg + nivolumab 3 mg/kg every 3 weeks  
Phase 1aE: Monotherapy or Combination Exploration Cohorts 
Cabiralizumab monotherapy or combination therapy in patients with selected 
advanced cancers  
Up to 40 patients may be enrolled to further characterize safety, PK, and PD at 
alternative dose levels or dosing schedules (not to exceed the MTD) 
Phase 1b: Combination Dose Expansion Cohorts 
Cabiralizumab and nivolumab combination therapy in patients with selected 
advanced cancers 
• Cohort 1b1: NSCLC (PD-1 naive) 
• Cohort 1b2: NSCLC  
(De novo or acquired resistance to anti-PD-1 targeting drug)  
 
• Cohort 1b3: Squamous Cell Carcinoma of the Head and Neck (SCCHN) 
• Cohort 1b4: Pancreatic Cancer 
• Cohort 1b5: Advanced Ovarian Cancer  
• Cohort 1b6: Renal Cell Carcinoma 
• Cohort 1b7: Malignant Glioma (GBM) 

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Number of Patients 
The total number of patients planned for this study is estimated to be 295 in 
North America.  
 
Study Population 
Inclusion Criteria for All Cohorts 
For entry into the study, all of the following criteria must be met. 
1. 
Patients must have at least one measurable lesion at baseline by 
computed tomography (CT) or magnetic resonance imaging (MRI) as per 
RECIST v1.1 criteria. 
a. 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. 
b. Sites for biopsy must be distinct from target lesions used for efficacy 
assessment. 
 
2. 
Patients must have had progressive disease on, after, or refused, 
appropriate approved therapy for their tumor type unless otherwise 
specified in the cohort specific criteria; for example, all non small-cell 
lung cancer (NSCLC) patients should have progressed on or after (or 
deemed to be unsuitable for) platinum doublet chemotherapy, and 
appropriate approved therapy for patients with EGFR or ALK mutations. 
3. 
All patients in Phase 1a and patients who consent to be biopsied in 
Phase 1b must have at least 1 tumor site that can be biopsied and be 
willing to have pre-treatment and on-treatment tumor and skin biopsies 
(optional for patients in the GBM cohort). Biopsies will be performed 
according to the treating institution’s own guidelines from a minimum of 
10 patients in each Phase 1b cohort. If biopsy has been performed and 
adequate sample collected as part of the patient’s standard of care within 
28 days prior Cycle 1 Day 1, it does not need to be repeated if the sample 
is available. 
4. 
Understand and sign an IRB/IEC-approved ICF prior to any study-
specific evaluation 
5. 
Age ≥18 years 
6. 
ECOG performance status of 0 or 1 
7. 
Willing and able to comply with all study procedures 
8. 
Prior focal radiotherapy must be completed at least 2 weeks before first 
dose of study drug administration. No radiopharmaceuticals (strontium, 
samarium) within 8 weeks before first dose of study drug administration. 
9. 
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 and patients should have recovered. 

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Study Population 
(cont.) 
10. Screening laboratory values must meet the following criteria: 
 
Hematologic 
a. Neutrophils ≥1500 cells/ µL 
b. Platelets ≥100 x 103/ µL 
c. Hemoglobin ≥9.0 g/dL 
 
 
Serum creatinine ≤1.5x ULN or creatinine clearance 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) 
d. PT/INR ≤ 1.5x ULN and PTT (aPTT) ≤ 1.5x ULN 
 
Hepatic 
a. AST or ALT ≤3x ULN  
b. Bilirubin ≤1.5x ULN (except patients with Gilbert's syndrome, who 
must have total bilirubin <3 mg/dL) 
c. Albumin >3.0 g/dL (pancreatic cancer patients only) 
 
11. Women of childbearing potential (WOCBP) must have a negative serum 
β-human chorionic gonadotropin (β-hCG) at screening and agree to use a 
reliable form of contraception (e.g., oral contraceptives, intrauterine 
device, or double barrier method of condom and spermicide) for at least 
28 days prior to the dosing of any study drug and for at least 23 weeks 
after the last dose of any study drug.  
12. Men who are sexually active with WOCBP must agree to follow 
instructions for method(s) of contraception for the duration of treatment 
with study drugs plus 31 weeks post-treatment completion. 
For additional cohort-specific inclusion criteria, refer to Section 3.2.4. 
 
Exclusion Criteria for All Cohorts  
Patients who meet ANY of the following criteria will be excluded from study 
entry.  
1. 
Current or history of clinically significant muscle disorders (e.g., 
myositis), recent unresolved muscle injury, or any condition known to 
elevate serum CK levels  

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Study Population 
(cont.) 
2. 
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 study drug 
administration except in the case of tumor-related AE treatment. Patients 
with a condition requiring chronic systemic treatment with either 
corticosteroids (inhaled or topical steroids and adrenal replacement 
steroid doses >10 mg/day prednisone equivalent) or other 
immunosuppressive medications within 2 weeks of treatment are 
permitted in the absence of active autoimmune disease (except for 
patients with glioma). 
 
3. 
Decreased cardiac function with NYHA > Class 2  
4. 
Uncontrolled or significant heart disorder such as unstable angina 
5. 
Significant abnormalities on ECG at screening. QTcF >450 msec for 
males or >470 msec for females at screening 
6. 
History of anti-drug antibodies, severe allergic, anaphylactic, or other 
infusion-related reaction to a previous biologic agent 
7. 
Known history of sensitivity to infusions containing Tween 20 
(polysorbate 20) and Tween 80 (polysorbate 80)  
8. 
Consumption of non-pasteurized milk while on study drug and for 30 
days after discontinuing study drug 
 
9. 
Non-oncology vaccine therapies for prevention of infectious diseases 
(e.g., HPV vaccine) within 4 weeks of study drug administration. 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 (i.e., 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 
vaccine. 
10. 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 pose a risk to patient safety 
11. Positive test for latent tuberculosis (TB) at screening (e.g. T-SPOT or 
Quantiferon test) or evidence of active TB 
12.  Patients with abnormal serum chemistry values, which in the opinion of 
the Investigator is considered to be clinically significant, will be 
excluded from the study. This will include 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 (e.g. hypokalemia or hyponatremia). 

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Study Population 
(cont.) 
13. Lack of peripheral venous or central venous access or any condition that 
would interfere with drug administration or collection of study samples 
14. 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 
15. Concomitant use of statins while on study. However, a patient using 
statins for over 3 months prior to study drug administration and in stable 
status without CK rise may be permitted to enroll. 
 
16. Pregnant or breastfeeding 
17. 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. 
18. Treatment with any anti-cancer therapy or participation in another 
investigational drug or biologics trial within 28 days or ≤ 5 half-lives 
(whichever is shorter) prior to first dose of study drug administration or 
while on this study  
19. Known history of testing positive for human immunodeficiency virus 
(HIV) 1 or 2 or known acquired immunodeficiency syndrome (AIDS) 
20. Positive test for hepatitis B virus surface antigen (HBsAg) or detectable 
hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or 
chronic infection 
21. Symptomatic interstitial lung disease or inflammatory pneumonitis 
 
22. Untreated or active central nervous system (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 prior to first dose of study drug administration. In 
addition, patients must be either off corticosteroids, or on a stable dose or 
decreasing dose of ≤ 10 mg daily prednisone or prednisone equivalent 
(except for patients with glioma). 
23. Evidence of coagulopathy or bleeding diathesis 
24. Any uncontrolled inflammatory GI disease including Crohn’s Disease 
and ulcerative colitis 
25. Prior exposure to any CSF1R pathway inhibitors 
26. Transfusion completed within 72 hours prior to first dose of study drug 
administration 
For additional cohort-specific exclusion criteria, refer to Section 3.2.4. 

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Dose-Modification 
Criteria 
 
Dose reductions for cabiralizumab and nivolumab are not permitted.  
 
 
 
 
 
  
 
 
 
 
 
 
Withdrawal 
Criteria 
Patients must discontinue study drugs for any of the following reasons: 
• Withdrawal of informed consent (patient’s decision to withdraw for any 
reason) 
• Any clinically significant AE, abnormal laboratory test results, or 
intercurrent illness which, in the opinion of the Investigator, indicates that 
continued participation in the study is not in the best interest of the patient 
• Patients who are required to have prohibited concomitant medications 
• Pregnancy 
• Termination of the study by the Sponsor 
• Loss of ability to freely provide consent through imprisonment or 
involuntary incarceration for treatment of a psychiatric or physical (e.g., 
infectious disease) illness 
 
• Documented disease progression or clinical deterioration while receiving 
active study therapy 
‒ 
Patients who receive cabiralizumab in combination with nivolumab 
may continue beyond disease progression at the discretion of the 
Investigator and in consultation with the Sponsor 
• Non-compliance by the patient 

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Study Endpoints 
 
Phase 1a Endpoints 
 
Primary 
Safety  
• 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 
Secondary 
Pharmacokinetic: The following PK parameters will be derived from 
concentration-time data for cabiralizumab when appropriate and applicable. 
Other parameters, such as dose dependency and accumulation ratio, may also 
be calculated. Accumulation ratio of Cmax and Cmin for nivolumab may be 
calculated if the data are available.  
• Area under serum concentration-time curve (AUC) 
• Maximum serum concentration (Cmax) 
• Minimum serum concentration (Cmin) 
• Clearance (CL) 
• Volume of distribution at steady state (Vss) 
Immunogenicity: Defined as an immune response to either cabiralizumab or 
nivolumab, will be assessed by measurement of total anti-FPA008 antibodies 
and total anti-nivolumab antibodies from all patients. Immunogenicity testing 
will consist of screening, confirmation, and titration for both cabiralizumab 
and nivolumab. 
Pharmacodynamic Biomarkers  
• Changes in whole blood monocyte subsets by flow cytometry 
• Changes in cytokine levels by multiplex analysis 
Change in macrophage and T-cell levels in tumor biopsy samples 
 
  
 
 
 
 
 
 
 
 
 
 
 

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Phase 1b Endpoints 
 
Primary 
Efficacy  
• ORR will be defined as the total number of patients with confirmed 
responses of either CR or divided by the total number of patients who are 
evaluable for a response per RECIST 1.1 by investigator assessment 
 
Safety 
• The incidence of AEs, SAEs, clinical laboratory abnormalities, and ECG 
abnormalities 
• The incidence of treatment discontinuations, modifications, and 
interruptions due to adverse events  
• Grade 3 and Grade 4 AEs and clinical laboratory abnormalities 
Secondary 
Pharmacokinetic: The following PK parameters will be derived from 
concentration-time data for cabiralizumab when appropriate and applicable. 
Other parameters, such as dose dependency and accumulation ratio, may also 
be calculated. Accumulation ratio of Cmax and Cmin for nivolumab may be 
calculated if the data are available.  
• Area under serum concentration-time curve (AUC) 
• Maximum serum concentration (Cmax) 
• Minimum serum concentration (Cmin)  
• Clearance (CL)  
• Volume of distribution at steady state (Vss) 
Immunogenicity: Defined as an immune response to either cabiralizumab or 
nivolumab, will be assessed by measurement of total anti-FPA008 antibodies 
and total anti-nivolumab antibodies from all patients. Immunogenicity testing 
will consist of screening, confirmation, and titration for both cabiralizumab 
and nivolumab. 
 
Pharmacodynamic Biomarkers  
• Changes in whole blood monocyte subsets by flow cytometry 
• Changes in cytokine levels by multiplex analysis 
• Change in macrophage and T-cell levels in tumor biopsy samples 
Efficacy  
• OS will be defined as the time between the first dose of study drug and 
death. 
– 
One-year OS 
– 
Median OS 

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Phase 1b 
Endpoints (cont.) 
 
Secondary (cont.) 
• DOR will be defined as the time from response (CR or PR) until the onset of 
PD.  
• PFS will be defined for each patient as the time from the first dose to the 
first observation of disease progression or death due to any cause. 
 
 
• 
ORR by Independent Radiology Review 
  
 
 
 
 
 
 
 
 
 
Schedule of 
Assessments 
See the following appendices for the Schedule of Assessments. 
Appendix A: Schedule of Assessments – Phase 1a Cabiralizumab 
Monotherapy and Combination 
Appendix B: Schedule of Assessments – Phase 1b Cabiralizumab + 
Nivolumab 
 

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3.1.2.1 
Phase 1a Monotherapy Cohorts and Combination 
Dose Escalation Cohorts ....................................................................... 66 
3.1.2.1.1 
Dose Limiting Toxicity ................................................................. 69 
3.1.2.2 
Phase 1a Extended Treatment Period .................................................... 70 
3.1.2.3 
Phase 1a 3-week Dosing Regimen Cohort ............................................ 70 
3.1.2.4 
Phase 1a Exploration Cohorts ............................................................... 70 
3.1.2.5 
Phase 1b Expansion Cohorts ................................................................. 70 
3.1.3 
End-of-Treatment Follow-up Period .............................................................70 
3.1.4 
Long-Term Follow-up ..................................................................................71 
3.1.5 
Study Duration ..............................................................................................71 
3.1.6 
Stopping Rules ..............................................................................................71 
3.1.6.1 
Stopping Rules for All Cohorts ............................................................. 71 
3.1.6.2 
Stopping Rules for Clinical Deterioration ............................................. 71 
3.2 
Study Population ......................................................................................................72 
3.2.1 
Planned Number of Patients and Study Centers ...........................................72 
3.2.2 
Inclusion Criteria for All Cohorts .................................................................72 
3.2.3 
Exclusion Criteria for All Cohorts ................................................................74 
3.2.4 
Additional Inclusion and Exclusion Criteria for Selected Cohorts ...............76 
3.2.4.1 
Phase 1a  Includes Phase 1a Dose Escalation, Phase 1a Exploration 
and Phase 1a 3-week Dosing Regimen cohorts .................................... 76 
3.2.4.1.1 
Cabiralizumab Monotherapy Cohorts ........................................... 76 
3.2.4.1.2 
Cabiralizumab + Nivolumab Combination Cohorts ...................... 76 
3.2.4.2 
Phase 1b ................................................................................................ 77 
3.2.4.2.1 
Cohort 1b1: Non-Small Cell Lung Cancer (PD-1 Naïve) ............. 77 
3.2.4.2.2 
Cohort 1b2: Non-Small Cell Lung Cancer  (De novo or Acquired 
Resistance to Anti-PD-1 Targeting Drugs) ................................... 78 
3.2.4.2.3 
Cohort 1b3: Squamous Cell Carcinoma of the Head and Neck .... 78 
3.2.4.2.4 
Cohort 1b4: Pancreatic Cancer ...................................................... 79 
3.2.4.2.5 
Cohort 1b5: Advanced Ovarian Cancer ........................................ 79 
3.2.4.2.6 
Cohort 1b6: Renal Cell Carcinoma ............................................... 80 
3.2.4.2.7 
Cohort 1b7: Malignant Glioma ..................................................... 80 
3.2.5 
Women of Childbearing Potential ................................................................81 
 
 
 
 

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3.4 
Discontinuation of Patients following any Treatment with Study Drug .............82 
3.5 
Long-Term Follow-up ..............................................................................................83 
4. 
Study Drugs ............................................................................................................. 84 
4.1 
Investigational Products ..........................................................................................84 
4.2 
Handling and Dispensing .........................................................................................84 
4.2.1 
Cabiralizumab ...............................................................................................84 
4.2.2 
Nivolumab.....................................................................................................85 
4.3 
Study Drug Dosing and Dose Modification ............................................................85 
4.3.1 
Dosing ...........................................................................................................85 
4.3.1.1 
Nivolumab Dosing ................................................................................ 85 
4.3.1.2 
Cabiralizumab Dosing ........................................................................... 86 
4.3.2 
Dose Delay for Cabiralizumab and Nivolumab ............................................86 
4.3.3 
Criteria to Resume Treatment with Cabiralizumab and Nivolumab ............87 
4.3.4 
Dose Reduction with Cabiralizumab and Nivolumab ..................................87 
4.3.5 
Dose Discontinuation Criteria for Cabiralizumab and Nivolumab ...............87 
4.3.6 
Infusion Delays and Missed Doses with Cabiralizumab and Nivolumab .....89 
4.3.7 
Intra-Patient Dose Escalation with Cabiralizumab and Nivolumab .............90 
4.3.8 
Treatment beyond Disease Progression with Cabiralizumab and Nivolumab
.......................................................................................................................90 
4.3.9 
Dose Modification Algorithms for Immuno-Oncology Agents....................91 
4.3.10 Treatment of Cabiralizumab and Nivolumab-Related Infusion Reactions ...91 
4.4 
Method of Assigning Patient Identification ...........................................................93 
4.5 
Blinding/Unblinding .................................................................................................94 
4.6 
Treatment Compliance ............................................................................................94 
4.7 
Destruction of Study Drug .......................................................................................95 
4.8 
Return of Study Drug ...............................................................................................95 
5. 
Study Assessments and Procedures ...................................................................... 96 
5.1 
Schedule of Assessments ..........................................................................................96 

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5.2 
Study Procedures by Visit .......................................................................................96 
5.2.1 
Phase 1a Monotherapy ..................................................................................96 
5.2.1.1 
Screening Period (Day –28 to Day 0) ................................................... 96 
5.2.1.2 
Cycle 1, Day 1 ....................................................................................... 97 
5.2.1.3 
Cycle 1, Day 2 ....................................................................................... 98 
5.2.1.4 
Cycle 1, Day 4 ....................................................................................... 98 
5.2.1.5 
Cycle 1, Day 8 ....................................................................................... 98 
5.2.1.6 
Cycle 2, Day 1 ....................................................................................... 99 
5.2.1.7 
End of the DLT Period (Phase 1a Dose Escalation cohorts only) ......... 99 
5.2.1.8 
Extended Treatment – Subsequent Cycles, Day 1 .............................. 100 
5.2.1.9 
End-of-Treatment Follow-up Period ................................................... 101 
5.2.2 
Phase 1a Combination (including 1aC, 1aE, and 1aD cohorts) ..................102 
5.2.2.1 
Screening Period (Day –28 to Day 0) ................................................. 102 
5.2.2.2 
Cycle 1, Day 1 ..................................................................................... 103 
5.2.2.3 
Cycle 1, Day 2 ..................................................................................... 104 
5.2.2.4 
Cycle 1, Day 4 ..................................................................................... 104 
5.2.2.5 
Cycle 1, Day 8 ..................................................................................... 105 
5.2.2.6 
Cycle 1, Day 15 (Cohort 1aD only) .................................................... 105 
5.2.2.7 
Cycle 2, Day 1 ..................................................................................... 106 
5.2.2.8 
End of DLT Period (Phase 1a Dose Escalation cohorts only) ............ 107 
5.2.2.9 
Extended Treatment – Subsequent Cycles, Day 1 .............................. 107 
5.2.2.10 
Cycle 8, Day 15 (Cohort 1aD only) .................................................... 109 
5.2.2.11 
End-of-Treatment Follow-up Period ................................................... 110 
5.2.3 
Phase 1b Combination Dose Expansion .....................................................110 
5.2.3.1 
Screening Period (Day –28 to Day 0) ................................................. 110 
5.2.3.2 
Cycle 1, Day 1 ..................................................................................... 111 
5.2.3.3 
Cycle 1, Day 2 ..................................................................................... 113 
5.2.3.4 
Cycle 1, Day 4 ..................................................................................... 113 
5.2.3.5 
Cycle 1, Day 8 ..................................................................................... 113 
5.2.3.6 
Cycle 2, Day 1 ..................................................................................... 114 
5.2.3.7 
Cycle 3 and Subsequent Cycles, Day 1 ............................................... 115 
5.2.3.8 
End-of-Treatment Follow-up Period ................................................... 117 
5.2.4 
Long-Term Follow-up for All Patients .......................................................118 
5.3 
Study Assessments ..................................................................................................118 

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5.3.1 
Safety Assessments .....................................................................................118 
5.3.2 
Efficacy Assessments ..................................................................................119 
5.3.2.1 
Primary Efficacy Parameters ............................................................... 119 
5.3.2.1.1 
Tumor Assessment ...................................................................... 119 
5.3.2.2 
Additional Efficacy Parameters .......................................................... 120 
5.3.2.3 
Tumor Biopsy or Fresh Tumor Tissue Collection .............................. 120 
5.3.2.4 
Skin Biopsy Tissue Collection ............................................................ 120 
5.3.3 
Pharmacokinetic Assessments ....................................................................121 
5.3.3.1 
Pharmacokinetic Collection and processing ....................................... 121 
5.3.3.2 
Pharmacokinetic Sample Analysis ...................................................... 121 
5.3.4 
Immunogenicity Assessments .....................................................................121 
5.3.5 
Biomarker Assessments ..............................................................................121 
5.3.5.1 
Skin Tissue and Tumor Tissue Specimens .......................................... 122 
5.3.5.2 
Serum .................................................................................................. 122 
 
 
5.3.5.4 
Flow Cytometry .................................................................................. 123 
 
 
6. 
Adverse Events ...................................................................................................... 124 
6.1 
Collection of Adverse Events .................................................................................124 
6.2 
Serious Adverse Events ..........................................................................................124 
6.2.1 
Serious Adverse Event Reporting ...............................................................126 
6.3 
Non-Serious Adverse Events .................................................................................126 
6.3.1 
Non-serious Adverse Event Reporting .......................................................126 
6.4 
Laboratory Test Result Abnormalities .................................................................127 
6.5 
Pregnancy ................................................................................................................127 
6.6 
Overdose ..................................................................................................................127 
6.7 
Potential Drug Induced Liver Injury ...................................................................128 
7. 
Statistical Considerations ..................................................................................... 129 
7.1 
Sample Size Determination ....................................................................................129 
7.2 
Populations for Analyses ........................................................................................129 

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7.3 
Endpoints ................................................................................................................129 
7.3.1 
Phase 1a Endpoints .....................................................................................129 
7.3.1.1 
Primary ................................................................................................ 129 
7.3.1.2 
Secondary ............................................................................................ 130 
 
 
7.3.2 
Phase 1b Endpoints .....................................................................................130 
7.3.2.1 
Primary ................................................................................................ 130 
7.3.2.2 
Secondary ............................................................................................ 131 
 
 
7.4 
Analyses ...................................................................................................................132 
7.4.1 
Demographics and Baseline Characteristics ...............................................132 
7.4.2 
Efficacy Analyses .......................................................................................132 
7.4.3 
Safety Analyses ...........................................................................................132 
7.4.4 
Pharmacokinetic Analyses ..........................................................................133 
7.4.5 
Immunogenicity ..........................................................................................133 
 
 
7.5 
Interim Analysis .....................................................................................................135 
8. 
Cohort Review Committee ................................................................................... 136 
9. 
Ethical Considerations ......................................................................................... 137 
9.1 
Good Clinical Practice ...........................................................................................137 
9.2 
Institutional Review Board/Independent Ethics Committee ..............................137 
9.3 
Informed Consent ...................................................................................................137 
10. Study Management ............................................................................................... 139 
10.1 Compliance ..............................................................................................................139 
10.1.1 Compliance with the Protocol and Protocol Revisions ...............................139 
10.1.2 Monitoring ..................................................................................................139 
10.1.2.1 
Source Documentation ........................................................................ 140 
10.1.3 Investigational Site Training .......................................................................140 
10.2 Records ....................................................................................................................140 
10.2.1 Records Retention .......................................................................................140 

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10.2.2 Study Drug Records ....................................................................................141 
10.2.2.1 
Case Report Forms .............................................................................. 141 
 
 
12. Appendices ............................................................................................................. 147 

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List of Abbreviations and Definitions 
ACTH 
Adrenocorticotropic hormone 
ADA 
Anti-drug antibody 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANA 
Antinuclear antibody 
ANC 
Absolute neutrophil count 
AST 
Aspartate aminotransferase 
AT 
Aminotransferase 
AUC 
Area under the concentration-time curve 
β-HCG 
Beta-human chorionic gonadotropin 
BID 
Bis in die; twice daily 
BMI 
Body mass index 
BMS 
Bristol-Myers Squibb 
BOR 
Best overall response 
BP 
Blood pressure 
BTLA 
B- and T-lymphocyte attenuator 
BUN 
Blood urea nitrogen 
ºC 
Degrees Celsius 
CBC 
Complete blood count 
CD 
Cluster of differentiation 
CEA 
Carcinoembryonic antigen 
CFR 
Code of Federal Regulations  
CHO 
Chinese hamster ovary 
CI 
Confidence interval 
CK 
Creatine kinase 
CL 
Clearance 
Cmax 
Maximum observed concentration 
Cmin 
Minimum observed concentration 
CMV 
Cytomegalovirus 
CNS 
Central nervous system 
CR 
Complete response 

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CRC 
Colorectal cancer 
CRF 
Case report form, may be paper or electronic 
CRO 
Contract research organization 
CRP 
C-reactive protein 
CSF1 
Colony stimulating factor 1 
CSF1R 
Colony stimulating factor 1 receptor 
CSR 
Clinical study report 
CT 
Computed tomography 
CTA 
Clinical trials agreement 
CTCAE v 4.03 
Common Terminology Criteria for Adverse Events, version 4.03 
CTLA-4 
Cytotoxic T lymphocyte antigen 4 
CTX 
C-terminal collagen crosslink peptides 
CV 
Coefficient of variation 
DC 
Dendritic cell 
DILI 
Drug-induced liver injury 
dL 
Deciliter 
DLT 
Dose-limiting toxicity 
DMARD 
Disease-modifying anti-rheumatic drug 
DNA 
Deoxyribonucleic acid 
DOR 
Duration of response 
dt-TGCT 
Diffuse-type tenosynovial giant-cell tumor 
EC50 
Half-maximal effective concentration 
ECG 
Electrocardiogram 
ECLA 
Electrochemiluminescence assay 
ECM 
Extracellular matrix 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EDTA 
Ethylene diamine tetraacetic acid 
e.g. 
exempli gratia (for example) 
ELISA 
Enzyme-linked immunosorbent assay 
ePPND 
Enhanced pre- and post-natal development 

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ESR 
Erythrocyte sedimentation rate 
ºF 
Degrees Fahrenheit 
FACS 
Fluorescent-activated cell sorter 
Fc 
Fragment crystallizable 
FDA 
Food and Drug Administration 
FFPE 
Formalin-fixed, paraffin-embedded 
FISH 
Fluorescent in situ hybridization 
FivePrime 
Five Prime Therapeutics, Inc. 
FOXP3+ 
Forkhead box p3  
FSH 
Follicle stimulating hormone 
g 
Gram 
GBM 
Malignant glioma 
GCP 
Good Clinical Practice 
GI 
Gastrointestinal 
h 
Hour 
HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B virus 
HCV 
Hepatitis C virus 
HIV 
Human Immunodeficiency Virus 
HR 
Heart rate 
HRT 
Hormone replacement therapy 
IB 
Investigator’s Brochure 
IC50 
Half-maximal inhibitory concentration 
ICD 
Implantable cardioverter defibrillator 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization  
ICOS 
Inducible co-stimulator 
i.e. 
id est (that is) 
IEC 
Independent ethics committee 
IFN 
Interferon 
IgG 
Immunoglobulin G 
IHC 
Immunohistochemistry 

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IL 
Interleukin 
IM 
Intramuscular 
IMP 
Investigational medicinal product 
IND 
Investigational new drug 
INR 
International normalized ratio 
I-O 
Immuno-oncology 
irAE 
Immune-related adverse event 
IRB 
Institutional review board 
ITIM 
Immunoreceptor tyrosine inhibitory motif 
ITSM 
Immunoreceptor tyrosine-based switch motif 
IU 
International unit 
IV 
Intravenous 
IXRS 
Integrated voice and web response system 
kg 
Kilogram 
KM 
Kaplan-Meier 
LAG-3 
Lymphocyte-activate gene 3 
LDH 
Lactate dehydrogenase 
LFT 
Liver function test 
LOQ 
Limit of quantitation 
MABEL 
Minimum anticipated biological effect level 
mCRPC 
Metastatic castration-resistant prostate cancer 
MDSC 
Myeloid-derived suppressor cell 
mg 
Milligram 
min 
Minute 
µL 
Microliter 
mL 
Milliliter 
MLR 
Mixed lymphocyte reaction 
µM 
Micrometer 
mM 
Millimolar 
mm3 
Cubic millimeters 
mmHg 
Millimeters of mercury 
MRI 
Magnetic resonance imaging 

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MSD 
Meso Scale Discovery 
MTD 
Maximum tolerated dose 
N 
Number of patients or observations 
NCI 
National Cancer Institute 
ng 
Nanogram 
NOAEL 
No-observable-adverse-effect level 
NSCLC 
Non-small cell lung cancer 
NYHA 
New York Heart Association 
NSAID 
Non-steroidal, anti-inflammatory drug 
ORR 
Objective response rate 
OS 
Overall survival 
PBMC 
Peripheral blood mononuclear cell 
PD 
Pharmacodynamics 
PD-1 
Programmed cell death 1 
PDAC 
Pancreatic ductal adenocarcinoma 
PD-L1 
Programmed death ligand 1 
PD-L2 
Programmed death ligand 2 
PFS 
Progression-free survival 
PK 
Pharmacokinetics 
PO 
Per os; by mouth 
PPK 
Population pharmacokinetics 
PR 
Partial response 
PT 
Prothrombin time 
PTT (aPTT) 
Partial thromboplastin time 
PVC 
Polyvinyl chloride 
q2w 
Every two weeks 
PVNS 
Pigmented villonodular synovitis 
qPCR 
Quantitative real-time polymerase chain reaction 
qRT-PCR 
Quantitative reverse-transcription polymerase chain reaction 
QTcF 
Fridericia’s correction formula for QT interval 
RA 
Rheumatoid arthritis 
RBC 
Red blood cell 

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RCC 
Renal cell carcinoma 
RD 
Recommended Dose 
RECIST v1.1 
Response Evaluation Criteria in Solid Tumors, version 1.1 
RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SCCHN 
Squamous-cell carcinoma of the head and neck 
SD 
Stable disease 
SkTnI 
Skeletal troponin 
SOP 
Standard operating procedure 
Src 
Sarcoma homology protein 
T3 
Triiodothyronine 
T4 
Thyroxine 
TAM 
Tumor-associated macrophage 
TB 
Tuberculosis 
TCR 
T-cell receptor 
TIL 
Tumor-infiltrating lymphocyte 
Tmax 
Time of maximum observed concentration 
TNF 
Tumor necrosis factor 
Trap5b 
Tartrate resistant acid phosphatases 5b 
ULN 
Upper limit of normal 
USP 
United States Pharmacopeia 
Vss 
Volume of distribution at steady state 
Vz 
Volume of distribution of terminal phase (if IV and if multi-exponential decline) 
WBC 
White blood cell 
WHO 
World Health Organization 
WOCBP 
Women of childbearing potential 
 

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2. 
Objectives 
2.1 
Phase 1a Objectives 
2.1.1 Primary 
• To assess the safety and tolerability of cabiralizumab as monotherapy 
• To assess the safety and tolerability of cabiralizumab in combination with nivolumab  
• To determine the recommended dose (RD) of cabiralizumab in combination with a fixed 
dose of nivolumab 
2.1.2 Secondary  
• To characterize the PK profile of cabiralizumab  
• To characterize the PK profile of nivolumab when administered in combination with 
cabiralizumab  
• To characterize the immunogenicity of cabiralizumab and nivolumab  
• To characterize the PD profile of cabiralizumab and nivolumab by analyses of biopsies 
(including IHC analyses of CD8, CD68, and other selected biomarkers)  
  
 
 
  
2.2 
Phase 1b Objectives 
2.2.1 Primary  
• To evaluate the clinical benefit of cabiralizumab in combination with nivolumab in 
patients with selected advanced cancers through the analysis of objective response rate 
(ORR) 
• To evaluate the safety and tolerability of cabiralizumab in combination with nivolumab in 
patients with selected advanced cancers treated at the RD  
2.2.2 Secondary  
• To evaluate the clinical benefit of cabiralizumab in combination with nivolumab in 
patients with selected advanced cancers through the analysis of overall survival (OS), 
duration of response (DOR), and progression free survival (PFS) 
• To characterize the PK profile of cabiralizumab when administered in combination with 
nivolumab 
• To characterize the PK profile of nivolumab when administered in combination with 
cabiralizumab  
• To characterize the immunogenicity of cabiralizumab and nivolumab  

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• To characterize the PD profile of cabiralizumab and nivolumab by analyses of biopsies 
(including IHC analyses of CD8, CD68, and other selected biomarkers)  
• To assess the association of selected biomarker measures and clinical efficacy measures 
using pre-treatment and on-treatment tumor biopsies  
  
 
 
 

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3. 
Investigational Plan 
3.1 
Study Design and Duration 
This study is a Phase 1a and 1b, open-label, multicenter, dose escalation and dose expansion 
study to evaluate the efficacy, safety, tolerability, PK, and PD of cabiralizumab as monotherapy 
and in combination with nivolumab in patients with selected advanced cancers. Cabiralizumab is 
a humanized monoclonal antibody directed against CSF1R, and nivolumab is a fully human 
monoclonal antibody directed against PD-1. For monotherapy arms of the study, cabiralizumab 
will be given on Day 1 of each 14-day treatment cycle. For the combination arms of the study, 
cabiralizumab and nivolumab will be given on Day 1 of each 14-day treatment cycle (except for 
the 3-week dosing regimen cohort). Nivolumab will be administered as an IV infusion over 
30 minutes followed by a 30 to 60-minute rest, and then cabiralizumab will be administered as 
an IV infusion over 30 minutes. If any Grade 3 or higher infusion reaction is observed during the 
proposed infusion rate of nivolumab 3 mg/kg over 30 minutes, the infusion rate will be extended 
to 60 minutes for all current and subsequent patients for the duration of this study.  
The study will include a Phase 1a dose escalation, Phase 1a 3-week dosing regimen, Phase 1a  
exploration and a Phase 1b dose expansion. Phase 1a dose escalation consists of 3 cabiralizumab 
monotherapy cohorts (1aM1,1aM2 and 1aM3) and 4 cohorts of cabiralizumab in combination 
with nivolumab (1aC1, 1aC2, 1aC3 and 1aC4). Phase 1a 3-week dosing regimen (1aD) consists 
of 1 cohort which will administer cabiralizumab in combination with nivolumab every three 
weeks instead of every two weeks. The Phase 1a exploration is designed to further evaluate the 
safety, PK, and PD of cabiralizumab as monotherapy and in combination with nivolumab. Phase 
1b consists of 7 cohorts (1b1 through 1b7) across 6 cancer types. Patients will be enrolled into 
either Phase 1a or Phase 1b of the study. The study design is shown in Figure 2. 
The study will consist of 3 periods including screening (up to 28 days), treatment, and follow-up.  
 

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Figure 2: FPA008-003 Study Design 
 
  
 
 

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3.1.1 Screening Period 
All screening evaluations must be completed and reviewed by the Investigator following the 
procedure noted in the Study Reference Manual for the enrollment process to confirm that 
patients meet all eligibility criteria before the first infusion of study drug. Written informed 
consent for participation in the study must be obtained before performing any study specific 
screening tests or procedures. Screening assessments will be performed within 28 days prior to 
the first dose of study drug unless otherwise specified. 
Study procedure-related AEs that occur after signing of the ICF and before administration of the 
first study drug dose will be collected during this period. 
3.1.2 Treatment Period  
3.1.2.1 
Phase 1a Monotherapy Cohorts and Combination Dose Escalation Cohorts  
Phase 1a consists of three cabiralizumab monotherapy cohorts and four dose-escalation cohorts 
of cabiralizumab in combination with nivolumab with a minimum of 3 patients enrolled in each 
cohort. The planned dose levels and schedules for the Phase 1a cohorts are as follows:  
• Cohort 1aM1: 2 mg/kg cabiralizumab, q2w 
• Cohort 1aM2: 6 mg/kg cabiralizumab, q2w 
• Cohort 1aM3: 4 mg/kg cabiralizumab, q2w 
– (Dose was de-escalated to 4 mg/kg after DLT observed in 1aM2 (See Section 1.9) 
• Cohort 1aC1: 1 mg/kg cabiralizumab + 3 mg/kg nivolumab, q2w 
• Cohort 1aC2: 2 mg/kg cabiralizumab + 3 mg/kg nivolumab, q2w 
• Cohort 1aC3: 4 mg/kg cabiralizumab + 3 mg/kg nivolumab, q2w 
• Cohort 1aC4: 6 mg/kg cabiralizumab + 3 mg/kg nivolumab, q2w 
The 2 mg/kg cabiralizumab monotherapy cohort (1aM1) was enrolled first, followed by 
enrollment in the 1 mg/kg cabiralizumab and nivolumab combination cohort (1aC1). Both 
cohorts cleared without any DLTs. The 2 mg/kg cabiralizumab and nivolumab combination 
cohort (1aC2) started after the DLT period cleared in the 1 mg/kg cabiralizumab and nivolumab 
combination cohort and 2 mg/kg cabiralizumab monotherapy cohort. 
The 6 mg/kg cabiralizumab monotherapy cohort (1aM2) opened after the DLT period cleared in 
the 2 mg/kg cabiralizumab monotherapy cohort (1aM1). There were two DLTs in patients treated 
in the 1aM2 cohort, both due to laboratory abnormalities. Subsequently, the dose was de-
escalated and Cohort 1aM3 (4 mg/kg cabiralizumab monotherapy) was opened. There were two 
DLTs in the 1aM3 monotherapy cohort and the protocol was subsequently amended to allow 
higher cutoffs for these laboratory values (see Section 1.8.1). Additional patients were added to 
the 1aM3 cohort to evaluate the DLT period under the new criteria.  

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The 4 mg/kg cabiralizumab and nivolumab combination cohort (1aC3) was opened after the 
DLT period cleared in the 1 mg/kg and 2 mg/kg cabiralizumab and nivolumab combination 
cohorts and in the respective cabiralizumab monotherapy cohorts.  
The 1aM2 cohort was also re-opened with the new DLT criteria. Upon successful completion of 
the DLT period the 6 mg/kg cabiralizumab and nivolumab combination cohort (1aC4) may be 
opened. 
Depending on the outcome of the cohorts described above, alternative dose cohorts may be 
opened. All dose escalation decisions will be based on assessment of DLTs, overall safety, and 
tolerability. Dose escalation decisions will be agreed upon between the Investigators and 
Sponsor. Prior to initiating each new dose level or expanding an existing dose level, a safety 
teleconference will be held wherein the Investigators and Sponsor will review patient data, 
including but not limited to demographics, dosing, concomitant medications, hematology, serum 
chemistry, and AEs; and confer and document agreement that dose escalation or expanding an 
existing dose level is considered appropriate. If the Investigators and Sponsor collectively agree, 
following review of safety, PK, and PD data (if available), that a different dose escalation 
scheme (e.g., an alternative dose of cabiralizumab monotherapy or in combination with 
nivolumab) should be used than the one outlined, this will be permitted. Review of safety, PK, 
and PD profiles may inform decisions to add cohorts with alternative dose levels or dose 
regimens (e.g., less frequent dosing) in order to reach an optimal target exposure. 
Dose escalation will be based on the number of DLTs experienced during the DLT evaluation 
interval as determined by the Medical Monitor and Investigators (see Section 3.1.2.1.1 for DLT 
criteria). The DLT evaluation interval begins on the first day of treatment and continues for 28 
days. Patients that receive at least 2 doses of study drug during the 28-day evaluation interval or 
patients who discontinue study treatment for drug-related AEs before receiving 2 doses of study 
drug will be considered evaluable for DLT determination. In consultation with Investigators, the 
Sponsor has the option to investigate alternative dose levels to those defined in the protocol.  
Dose escalation in Phase 1a will proceed as follows: 
• If none of the first 3 evaluable patients in a dose cohort experiences a DLT within the 
DLT evaluation interval, then the next 3 patients will be treated at the next higher dose 
cohort.  
• If 1 of the first 3 evaluable patients in a cohort experiences a DLT within the DLT 
evaluation interval, then 3 additional patients will be treated in that dose cohort.  
– If no more than 1 of the first 6 evaluable patients experiences a DLT during the DLT 
evaluation interval, then the next 3 patients will be enrolled at the next higher dose 
cohort.  
− If 2 of the first 6 evaluable patients in a cohort experience a DLT, that cohort will be 
expanded to 9 evaluable patients.  

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If the MTD is not reached during the Phase 1a combination dose escalation, or subsequent cycles 
of treatment in cleared Phase 1a combination cohorts provide additional insight on the safety 
profile, an RD may be selected based on overall tolerability, safety, PK, and PD (if available). 
Sponsor has the option to expand any cohort previously established to be safe in order to obtain 
additional data or to investigate alternative dose levels to those defined in the protocol. Upon 
completion of the DLT period, up to 40 additional patients may be enrolled in Phase 1aE to fully 
characterize safety, PK, and PD. 
If a patient in Phase 1a monotherapy does not receive 2 doses of study drug and does not 
complete safety assessments and if a patient in one of the Phase 1a combination cohorts does not 
receive 2 doses of each study drug and does not complete the safety assessment (e.g., safety lab 
and/or AE reporting) in the DLT period for reasons other than drug-related AEs (e.g., disease 
progression or withdrawal of consent), then an additional patient will be enrolled into the cohort 
so that the cohort has at least 3 patients evaluable for the DLT period. All such discussions and 
decisions will be documented as part of the dose escalation decision-making process.  
Upon completion of the DLT period, Phase 1a patients may participate in an Extended Treatment 
Period following the guidelines in Section 3.1.2.2.  
3.1.2.1.1 Dose Limiting Toxicity 
A DLT is defined as a study drug-related ≥ Grade 3 AE (using National Cancer Institute [NCI] 
Common Terminology Criteria for Adverse Events [CTCAE] v 4.03) occuring during the first 
28-days, excluding: 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, or a transient (resolving within 6 hours of onset) 
Grade 3 infusion-related AE. Any recurrence of Grade 3 rash, Grade 3 immune-related AE, or 
Grade 3 infusion-related AE will be considered a DLT. 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.  
In the absence of clinical symptoms and other accompanying changes in bilirubin or ALT (as 
noted in appendices F, G, and H), serum elevations of AST/ALT > 12 xULN and ≤ 20 xULN 
that last for < 7 days will not be considered a DLT and serum elevations of CK and/or 
LDH > 15 xULN and ≤ 20 xULN that last for < 7 days will not be considered a DLT.  
Upon the first occurrence of a delayed DLT in any patient enrolled in Phase 1a (defined as any 
DLT that occurs between 4 to 6 weeks after administration of study drug), all ongoing and 
subsequent DLT periods will be expanded to 42 days for all remaining and subsequent patients 
enrolled in Phase 1a dose escalation. If no patient experiences a delayed DLT, the DLT window 
will remain at 28 days for all patients. 

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3.1.2.2 
Phase 1a Extended Treatment Period 
Upon completion of the DLT period, patients from the Phase 1a monotherapy and combination 
cohorts may participate in an Extended Treatment Period.  
Patients from the Phase 1a monotherapy cohorts are allowed to continue to receive 
cabiralizumab monotherapy at the same cabiralizumab dose level and patients from the Phase 1a 
combination cohorts are allowed to continue to receive cabiralizumab in combination with 
nivolumab at the same dose levels until disease progression, unacceptable toxicity, or other 
reason for treatment discontinuation. 
3.1.2.3 
Phase 1a 3-week Dosing Regimen Cohort 
In protocol amendment 4, a 3-week dose regimen cohort (1aD) is added to characterize the PK 
profile and safety of cabiralizumab in combination with nivolumab when administered as an 
alternative dosing schedule. This Phase 1a 3-week Dosing Regimen consists of one cohort 
evaluating 4 mg/kg cabiralizumab in combination with 3 mg/kg nivolumab, administered 
intravenously every three weeks until disease progression, unacceptable toxicity, or other reason 
for treatment discontinuation. 
3.1.2.4 
Phase 1a Exploration Cohorts 
The Phase 1a exploration consists of up to 40 additional patients to further evaluate the safety, 
PK, and PD of cabiralizumab as monotherapy and in combination with nivolumab.  
3.1.2.5 
Phase 1b Expansion Cohorts  
To further characterize safety and efficacy of cabiralizumab in combination with nivolumab, 
Phase 1b will enroll up to 7 expansion cohorts in 6 advanced cancer types (1b1 through 1b7). 
Enrollment in Phase 1b will begin when an RD has been identified based on overall safety, 
tolerability, PK, and PD (if available) data.  
During enrollment of any expansion cohort, if the observed number of responses makes it 
unlikely to achieve a target response rate for that indication, then further recruitment to that 
cohort may be suspended or terminated. 
After initiation of Phase 1b, the dose may be changed based on data from continued dose 
exploration in Phase 1a. There will be no intra-patient dose modification and any alteration in 
dose for Phase 1b will only apply to newly enrolled patients in Phase 1b. 
3.1.3 End-of-Treatment Follow-up Period 
All patients should return to the clinic 28 (±7) days and 100 (±7) days from their last dose of 
study drug to complete the End-of-Treatment Follow-up Period, irrespective of whether a patient 
is discontinued from the study drug at a planned visit or mid-cycle. AEs will be assessed until 
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event reporting will continue until 100 (±7) days after the last dose of study drug or until 
initiation of subsequent anti-cancer therapy. 
3.1.4 Long-Term Follow-up 
Patients should continue onto Long-Term Follow-up after completing the End-of-Treatment 
Follow-up Period. 
Patients will be followed every 12 weeks for survival, or more frequently as needed. Patients 
who discontinue treatment while showing clinical benefit (complete response [CR], partial 
response [PR], or stable disease [SD]) should have tumor assessments during these visits for 
duration of response.  
Long-term Follow-up for survival may be conducted by telephone, rather than by an in-person 
visit, once tumor progression is determined or use of subsequent anti-cancer therapy has been 
initiated. During the Long-Term Follow-up Period, if the patient undergoes local therapy (e.g., 
resection, radiation) or new systemic therapy is initiated, this should be documented. 
3.1.5 Study Duration 
Patients who receive study drug(s) may continue as long as they experience clinical benefit in the 
opinion of the Investigator or until unacceptable toxicity or symptomatic deterioration attributed 
to disease progression as determined by the Investigator after an integrated assessment of 
radiographic data, biopsy results (if available), and clinical status, or withdrawal of consent. 
3.1.6 Stopping Rules 
3.1.6.1 
Stopping Rules for All Cohorts 
Management of drug-related toxicities will follow the adverse event management tables 
(Appendix F and Appendix G). Management of drug-related laboratory abnormalities will follow 
the management tables in Appendix H. 
The Sponsor will discuss such cases with the study Investigators as appropriate to determine 
further enrollment. IRBs may be notified by the Investigators of all cases and decisions regarding 
continued enrollment, according to applicable regulatory requirements or institution procedures.  
3.1.6.2 
Stopping Rules for Clinical Deterioration 
Accumulating clinical evidence indicates that the emergence of objective responses to agents that 
activate anti-tumor immune responses may follow delayed kinetics of weeks or months, and can 
be preceded by initial apparent progression of disease with the appearance of new lesions or 
some enlarging of lesions while certain index lesions are regressing (“mixed response”). 
Therefore, it is reasonable to allow patients who experience apparent progression to continue to 
receive treatment until progression is confirmed at the next imaging assessment. These 

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considerations should be balanced by clinical judgment as to whether the patient is clinically 
deteriorating and unlikely to receive any benefit from continued treatment. 
Such deterioration will be assessed to have occurred after a clinical event that, in the 
Investigator’s opinion, is attributable to disease progression and is unlikely to reverse with 
continued study treatment and therefore indicates that the patient is not benefiting from study 
treatment and cannot be managed by the addition of supportive care. The decision to continue 
treatment should be discussed with the Sponsor’s Medical Monitor or designee. Examples of 
events that may, in the Investigator’s opinion, indicate a lack of clinical benefit include but are 
not limited to the following: 
• Eastern Cooperative Oncology Group (ECOG) score increase of at least 2 points from 
baseline (e.g. from 0 to 2). 
• Habitual changes such as changes in activities and symptoms including reduction in 
appetite and/or sleep, altered awareness, and increased pain-related symptoms due to 
cancer. 
• Progression of disease confirmed by the treating Investigator. 
• Any setting where the initiation of new anti-neoplastic therapy has been deemed 
beneficial to the patient even in the absence of any such documented clinical events. 
3.2 
Study Population 
3.2.1 Planned Number of Patients and Study Centers 
The total number of patients planned for this study is estimated to be 295 in North America. By 
the end of the study, approximately 85 patients in Part 1a (approximately 20 in monotherapy 
dose escalation, 15 in combination dose escalation, 10 in an 3-week dose regimen, and up to 40 
in exploration cohorts) and 210 patients in Part 1b (approximately 30 patients for each of the 7 
Phase 1b cohorts) will be enrolled. There will be approximately 50 study centers participating in 
this study. 
3.2.2 Inclusion Criteria for All Cohorts 
For entry into the study, all of the following criteria must be met. 
1. 
Patients must have at least one measurable lesion at baseline by computed tomography 
(CT) or magnetic resonance imaging (MRI) as per RECIST v1.1 criteria. 
a. 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.b. Sites for biopsy must be distinct from target lesions used 
for efficacy assessment. 
2. 
Patients must have had progressive disease on, or refused, appropriate approved therapy for 
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NSCLC patients should have progressed on platinum doublet chemotherapy, and 
appropriate approved therapy for patients with EGFR or ALK mutations. 
3. 
All patients in Phase 1a and patients who consent to be biopsied in Phase 1b must have at 
least 1 tumor site that can be biopsied and be willing to have pre-treatment and on-
treatment tumor and skin biopsies (optional for patients in the GBM cohort). Biopsies will 
be performed according to the treating institution’s own guidelines from a minimum of 
10 patients in each Phase 1b cohort. If biopsy has been performed and adequate sample 
collected as part of the patient’s standard of care within 28 days prior Cycle 1 Day 1, it does 
not need to be repeated if the sample is available. 
4. 
Understand and sign an IRB/IEC-approved ICF prior to any study-specific evaluation 
5. 
Age ≥18 years 
6. 
ECOG performance status of 0 or 1 
7. 
Willing and able to comply with all study procedures 
8. 
Prior focal radiotherapy must be completed at least 2 weeks before first dose of study drug 
administration. No radiopharmaceuticals (strontium, samarium) within 8 weeks before first 
dose of study drug administration. 
9. 
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 and patients 
should have recovered. 
10. Screening laboratory values must meet the following criteria: 
 
Hematologic 
a. Neutrophils ≥1500 cells/ µL 
b. Platelets ≥100 x 103/ µL 
c. Hemoglobin ≥9.0 g/dL 
 
Serum creatinine ≤1.5x ULN or creatinine clearance 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) 
d. PT/INR ≤ 1.5 x ULN and PTT (aPTT) ≤ 1.5 x ULN 

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Hepatic 
a. AST or ALT ≤3 x ULN  
b. Bilirubin ≤1.5 x ULN (except patients with Gilbert's syndrome, who must have total 
bilirubin <3 mg/dL) 
c. Albumin >3.0 g/dL (pancreatic cancer patients only) 
11. Women of childbearing potential (WOCBP) must have a negative serum β-human 
chorionic gonadotropin (β-hCG) at screening and agree to use a reliable form of 
contraception (e.g., oral contraceptives, intrauterine device, or double barrier method of 
condom and spermicide) for at least 28 days prior to the dosing of any study drug and for at 
least 23 weeks after the last dose of any study drug.  
12. Men who are sexually active with WOCBP must agree to follow instructions for method(s) 
of contraception for the duration of treatment with study drugs plus 31 weeks post-
treatment completion. 
3.2.3 Exclusion Criteria for All Cohorts  
Patients who meet ANY of the following criteria will be excluded from study entry.  
1. 
Current or history of clinically significant muscle disorders (e.g., myositis), recent 
unresolved muscle injury, or any condition known to elevate serum CK levels  
2. 
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 study drug administration except in the case of tumor-related AE treatment. 
Patients with a condition requiring chronic systemic treatment with either corticosteroids 
(inhaled or topical steroids and adrenal replacement steroid doses >10 mg/day prednisone 
equivalent) or other immunosuppressive medications within 2 weeks of treatment are 
permitted in the absence of active autoimmune disease (except for patients with glioma).  
3. 
Decreased cardiac function with NYHA > Class 2  
4. 
Uncontrolled or significant heart disorder such as unstable angina 
5. 
Significant abnormalities on ECG at screening. QTcF >450 msec for males or >470 msec 
for females at screening 
6. 
History of anti-drug antibodies, severe allergic, anaphylactic, or other infusion-related 
reaction to a previous biologic agent 
7. 
Known history of sensitivity to infusions containing Tween 20 (polysorbate 20) and Tween 
80 (polysorbate 80)  
8. 
Consumption of non-pasteurized milk while on study drug and for 30 days after 
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9. 
Non-oncology vaccine therapies for prevention of infectious diseases (e.g., HPV vaccine) 
within 4 weeks of study drug administration. 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 (i.e., 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 vaccine. 
10. 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 pose a risk to patient safety 
11. Positive test for latent tuberculosis (TB) at screening (e.g. T-SPOT or Quantiferon test) or 
evidence of active TB 
12. Patients with abnormal serum chemistry values, which in the opinion of the Investigator is 
considered to be clinically significant, will be excluded from the study. This will include 
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 (e.g. hypokalemia or hyponatremia).  
13. Lack of peripheral venous or central venous access or any condition that would interfere 
with drug administration or collection of study samples 
14. 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 
15. Concomitant use of statins while on study. However, a patient using statins for over 
3 months prior to study drug administration and in stable status without CK rise may be 
permitted to enroll 
16. Pregnant or breastfeeding 
17. 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. 
18. Treatment with any anti-cancer therapy or participation in another investigational drug or 
biologics trial within 28 days or ≤ 5 half-lives (whichever is shorter) prior to first dose of 
study drug administration or while on this study 
19. Known history of testing positive for human immunodeficiency virus (HIV) 1 or 2 or 
known acquired immunodeficiency syndrome (AIDS) 

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20. Positive test for hepatitis B virus surface antigen (HBsAg) or detectable hepatitis C virus 
ribonucleic acid (HCV RNA) indicating acute or chronic infection  
21. Symptomatic interstitial lung disease or inflammatory pneumonitis 
22. Untreated or active central nervous system (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 prior to first dose of study drug administration. In addition, 
patients must be either off corticosteroids, or on a stable dose or decreasing dose of ≤10 mg 
daily prednisone or prednisone equivalent (except for patients with glioma). 
23. Evidence of coagulopathy or bleeding diathesis 
24. Any uncontrolled inflammatory GI disease including Crohn’s Disease and ulcerative colitis 
25. Prior exposure to any CSF1R pathway inhibitors 
26. Transfusion completed within 72 hours prior to first dose of study drug administration 
3.2.4 Additional Inclusion and Exclusion Criteria for Selected Cohorts 
3.2.4.1 
Phase 1a  
Includes Phase 1a Dose Escalation, Phase 1a Exploration and Phase 1a 3-week 
Dosing Regimen cohorts 
3.2.4.1.1 Cabiralizumab Monotherapy Cohorts  
Inclusion 
1. 
Histologically or cytologically confirmed solid tumor that is locally recurrent or metastatic 
and has progressed following standard treatment or is not appropriate for standard 
treatment 
2. 
Patients with squamous NSCLC must have documented progression on nivolumab in order 
to enroll in the monotherapy cohorts of the study. 
3.2.4.1.2 Cabiralizumab + Nivolumab Combination Cohorts  
Exclusion 
1. 
Prior exposure to any PD-1 pathway targeting drug 
a. 
This will not apply to additional patients enrolled in Phase 1a after completion of the 
DLT period to fully characterize safety, PK, and PD. 
2. 
Subjects with history of life-threatening toxicity related to prior immune therapy (e.g., anti-
CTLA-4 or anti-PD-1/PD-L1 treatment or any other antibody or drug specifically targeting 
T-cell co-stimulation or immune checkpoint pathways) except those that are unlikely to re-
occur with standard countermeasures (e.g., Hormone replacement after adrenal crisis) 

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3.2.4.2 
Phase 1b 
Exclusion 
1. 
Subjects with a history of life-threatening toxicity related to prior immune therapy 
(e.g., anti-CTLA-4 or anti-PD-1/PD-L1 treatment or any other antibody or drug specifically 
targeting T-cell co-stimulation or immune checkpoint pathways) except those that are 
unlikely to recur with standard countermeasures (e.g., Hormone replacement after adrenal 
crisis) 
3.2.4.2.1 Cohort 1b1: Non-Small Cell Lung Cancer (PD-1 Naïve) 
Inclusion 
1. 
Patients with histologically or cytologically documented non-small cell lung cancer 
(NSCLC) who present with Stage IIIB locally advanced or Stage IV metastatic disease 
(according to version 7 of the International Association for the Study of Lung Cancer 
Staging Manual in Thoracic Oncology) or with recurrent or progressive disease following 
multi-modal therapy (radiation therapy, surgical resection, or definitive chemoradiation)  
2. 
Objective evidence of disease progression during or after at least one ALK-targeting agent 
(if ALK mutation positive) or after at least one EGFR-targeting agent (if EGFR mutation 
positive) unless patient has refused these diagnostic tests or specific therapies. 
3. 
Disease progression or recurrence during/after a platinum doublet-based chemotherapy 
regimen for advanced or metastatic disease 
a. 
Maintenance therapy following platinum doublet-based chemotherapy is not 
considered a separate therapy regimen. 
b. 
Patients who received platinum-containing adjuvant, neoadjuvant or definitive 
chemoradiation therapy given for locally advanced disease, and developed recurrent 
(local or metastatic) disease within 6 months of completing therapy are eligible. 
c. 
Patients with recurrent disease > 6 months after platinum-containing adjuvant, 
neoadjuvant or definitive chemo-radiation therapy given for locally advanced disease, 
who also subsequently progressed during or after a platinum doublet-based regimen 
given to treat the recurrence, are eligible. 
Exclusion 
1. 
Has received prior therapy immune cell-modulating antibody regimens, such as, but not 
limited to anti-PD-1, anti-PD-L1, anti PD-L2, anti-CTLA-4, anti-CD137, anti-KIR, and/or 
anti-OX40 antibodies. 

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3.2.4.2.2 Cohort 1b2: Non-Small Cell Lung Cancer  
(De novo or Acquired Resistance to Anti-PD-1 Targeting Drugs) 
Inclusion 
1. 
Patients with histologically or cytologically documented NSCLC who present with 
Stage IIIB locally advanced or Stage IV metastatic disease. 
2. 
Patient has radiological evidence of disease progression after receiving at least 2 doses of 
an anti-PD-1 targeting drug (e.g. nivolumab,pembrolizumab) in either of the following 
settings: progressive disease as the initial best objective response (de novo resistance), or 
progressive disease after an initial response of either CR, PR or SD (acquired resistance). 
3. 
Objective evidence of disease progression during or after at least one ALK-targeting agent 
(if ALK mutation positive) or after at least one EGFR-targeting agent (if EGFR mutation 
positive) unless patient has refused these diagnostic tests or specific therapies. 
4. 
Disease progression or recurrence during/after a platinum doublet-based chemotherapy 
regimen for advanced or metastatic disease. 
a. 
Maintenance therapy following platinum doublet-based chemotherapy is not 
considered a separate therapy regimen. 
b. 
Patients who received platinum-containing adjuvant, neoadjuvant or definitive 
chemoradiation therapy given for locally advanced disease, and developed recurrent 
(local or metastatic) disease within 6 months of completing therapy are eligible. 
c. 
Patients with recurrent disease > 6 months after platinum-containing adjuvant, 
neoadjuvant or definitive chemo-radiation therapy given for locally advanced disease, 
who also subsequently progressed during or after a platinum doublet-based regimen 
given to treat the recurrence, are eligible. 
Exclusion 
1. 
Intolerance to any PD-1 targeting drug. 
 
Intolerance is defined as any treatment-related Grade 4 AE, or any treatment-related 
Grade 2 or Grade 3 AE that is unacceptable to the patient and persists despite standard 
countermeasures.  
2. 
Prior treatment with an mTOR inhibitor (including, but not limited to, everolimus, 
temsirolimus, sirolimus, and ridaforolimus). 
3.2.4.2.3 Cohort 1b3: Squamous Cell Carcinoma of the Head and Neck  
Inclusion 
1. 
Patients with histologically or cytologically documented recurrent or metastatic squamous 
cell carcinoma of the head and neck (SCCHN) (oral cavity, pharynx, larynx), stage III or IV 
and not amenable to local therapy with curative intent (surgery or radiation therapy with or 
without chemotherapy). 

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2. 
Tumor progression or recurrence within 6 months of the last dose of platinum therapy in the 
adjuvant (i.e. with radiation after surgery), primary (i.e., with radiation), recurrent, or 
metastatic setting or patients that are intolerant to platinum chemotherapy.  
Exclusion 
1. 
Histologically confirmed recurrent or metastatic carcinoma of the nasopharynx and any 
salivary gland or non-squamous histology. 
2. 
Has received prior therapy immune cell-modulating antibody regimens, such as, but not 
limited to anti-PD-1, anti-PD-L1, anti PD-L2, anti-CTLA-4, anti-CD137, anti-KIR, and/or 
anti-OX40 antibodies. 
3.2.4.2.4 Cohort 1b4: Pancreatic Cancer 
Inclusion 
1. 
Histologically or cytologically documented unresectable localized, borderline resectable, 
locally advanced or metastatic adenocarcinoma of the pancreas, which has failed, or is not 
indicated for standard therapy, or for which the patient has refused standard therapy 
2. 
Patients who may have received prior surgery, radiation therapy for the management of 
locally advanced or metastatic adenocarcinoma of the pancreas providing that disease 
progression has been documented. All toxicities should be resolved, and the last fraction of 
radiation treatment was completed at least 4 weeks prior to first study drug administration  
Exclusion 
1. 
Patients with islet cell neoplasms, neuroendocrine or other primary tumors in the pancreas 
2. 
Patients with active pancreatitis 
3. 
Has received prior therapy immune cell-modulating antibody regimens, such as, but not 
limited to anti-PD-1, anti-PD-L1, anti PD-L2, anti-CTLA-4, anti-CD137, anti-KIR, and/or 
anti-OX40 antibodies  
4. 
Ascites of Grade 2 or higher 
5. 
Albumin <3.0 g/dL 
3.2.4.2.5 Cohort 1b5: Advanced Ovarian Cancer 
Inclusion 
1. 
Patients with histologically or cytologically confirmed epithelial ovarian cancer, fallopian 
tube, or primary peritoneal cancer. 
2. 
Patients who have received at least three prior regimens of treatment. 

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Exclusion 
1. 
Has received prior therapy immune cell-modulating antibody regimens, such as, but not 
limited to anti-PD-1, anti-PD-L1, anti PD-L2, anti-CTLA-4, anti-CD137, anti-KIR, and/or 
anti-OX40 antibodies. 
3.2.4.2.6 Cohort 1b6: Renal Cell Carcinoma 
Inclusion 
1. 
Patients with histologically or cytologically confirmed advanced or metastatic renal cell 
carcinoma with a clear-cell component. 
2. 
Must have received at least one prior anti-angiogenic therapy regimens (including, but not 
limited to, sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and bevacizumab) in the 
advanced or metastatic setting. Prior cytokine therapy (eg, IL-2, IFN-α), vaccine therapy, or 
treatment with cytotoxics is also allowed.  
Exclusion 
1. 
Has received prior therapy immune cell-modulating antibody regimens, such as, but not 
limited to anti-PD-1, anti-PD-L1, anti PD-L2, anti-CTLA-4, anti-CD137, anti-KIR, and/or 
anti-OX40 antibodies. 
3.2.4.2.7 Cohort 1b7: Malignant Glioma 
Inclusion 
1. 
Histologically or cytologically documented advanced World Health Organization (WHO) 
Grade IV malignant glioma (glioblastoma or gliosarcoma). 
2. 
Previous treatment with radiotherapy and temozolomide. 
3. 
Documented first recurrence of GBM by diagnostic biopsy or contrast-enhanced MRI 
performed within 28 days of first study drug administration per Response Assessment in 
Neuro-oncology (RANO) criteria. 
4. 
If on steroids, dose must be stable or decreased for a minimum of 5 days prior to baseline 
MRI. 
Exclusion 
1. 
Prior treatment with bevacizumab or another VEGF- or VEGFR-targeting agent. 
2. 
Recent evidence of more than Grade 1 CNS hemorrhage on baseline MRI scan. 
3. 
History or evidence upon physiological/neurological exam of CNS disease (e.g., seizures) 
unrelated to cancer unless adequately controlled by medication or potentially interfering 
with the study treatment. 
4. 
Patients unable to have a head contrast-enhanced MRI due to a pre-existing medical 
condition including a pacemaker or implantable cardioverter defibrillator (ICD) device. 

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5. 
Has received prior therapy immune cell-modulating antibody regimens, such as, but not 
limited to anti-PD-1, anti-PD-L1, anti PD-L2, anti-CTLA-4, anti-CD137, anti-KIR, and/or 
anti-OX40 antibodies. 
3.2.5 Women of Childbearing Potential 
Women of childbearing potential (WOCBP) include any females who have experienced 
menarche and who have not undergone surgical sterilization (hysterectomy, bilateral tubal 
ligation, or bilateral oophorectomy), and who are not post-menopausal. Post-menopause is 
defined as: 
• Amenorrhea ≥12 consecutive months without another cause, and a documented serum 
follicle stimulating hormone (FSH) level >35 mIU/mL, or 
• Women with irregular menstrual periods and a documented serum FSH level 
>35 mIU/mL (Note: FSH level testing is not required for women ≥62 years old with 
amenorrhea of ≥1 year), or 
• Women on hormone replacement therapy (HRT). 
Women who are using oral or other hormonal contraceptives, such as vaginal products, skin 
patches, or implanted or injectable products, or mechanical products, such as an intrauterine 
device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or who are 
practicing abstinence or who have a sterile (e.g., vasectomy) partner should be considered to be 
of childbearing potential (Gabbay 2008, Kestelman 1991). 
 
 
 
 
 
  
 
 
 
 
 
 
 
 

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3.4 
Discontinuation of Patients following any Treatment with Study Drug  
Patients must discontinue study drugs for any of the following reasons: 
• Withdrawal of informed consent (patient’s decision to withdraw for any reason) 
• Any clinically significant AE, abnormal laboratory test results, or intercurrent illness 
which, in the opinion of the Investigator, indicates that continued participation in the 
study is not in the best interest of the patient 
• Patients who are required to have prohibited concomitant medications 

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• Pregnancy 
• Termination of the study by the Sponsor 
• Loss of ability to freely provide consent through imprisonment or involuntary 
incarceration for treatment of a psychiatric or physical (e.g., infectious disease) illness 
• Documented disease progression or clinical deterioration while receiving active study 
therapy 
• Non-compliance by the patient 
All patients who discontinue study treatment should comply with protocol specified follow-up 
procedures as outlined in Section 5.2.4. The only exception to this requirement is when a patient 
withdraws consent for all study procedures or loses the ability to consent freely (i.e., is 
imprisoned or involuntarily incarcerated for the treatment of a psychiatric or physical illness). 
If a patient was discontinued, the reason for discontinuation must be entered on the appropriate 
CRF. The date and reason for cessation of cabiralizumab and/or nivolumab will be documented, 
and the Investigator must make every effort to perform the End-of-Treatment Visits. Adverse 
event reporting will continue until 100 (±7) days after the last dose of study drug or until 
initiation of subsequent anti-cancer therapy. Patients with ongoing SAEs will be followed until 
resolution or stabilization.  
3.5 
Long-Term Follow-up  
Patients who discontinue treatment while still receiving clinical benefit (i.e., CR, PR or SD) 
should get follow-up tumor scans every 12 (±2) weeks until disease progression or use of 
subsequent anti-cancer therapy to determine the duration of response, unless consent is 
withdrawn.  
Long-Term Follow-up for survival may be conducted by telephone, rather than by an in-person 
visit, once tumor progression is determined or use of subsequent anti-cancer therapy has been 
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4. 
Study Drugs 
In this study, both study drugs, cabiralizumab and nivolumab, are considered Investigational 
Medicinal Products (IMP).  
4.1 
Investigational Products 
An investigational product, also known as investigational medicinal product in some regions, is 
defined as a pharmaceutical form of an active substance or placebo being tested or used as a 
reference in a clinical study, including products already having a marketing authorization but 
used or assembled (formulated or packaged) differently than the authorized form, or used for an 
unauthorized indication, or when used to gain further information about the authorized form. In 
this protocol, the investigational products are cabiralizumab and nivolumab. 
4.2 
Handling and Dispensing 
The investigational product should be stored in a secure area according to local regulations. It is 
the responsibility of the Investigator to ensure that investigational product is only dispensed to 
Patients. The investigational product must be dispensed only from official study sites by 
authorized personnel according to local regulations. 
The applicable site personnel should ensure that the study drugs are stored in accordance with 
the environmental conditions (temperature, light, and humidity) determined by the Sponsor. If 
concerns regarding the quality or appearance of the study drugs arise, do not dispense the study 
drugs and contact the Sponsor or designee immediately. 
Study drug documentation including all processes required to ensure drug is accurately 
administered must be maintained. This includes documentation of drug storage and 
administration and, as applicable, storage temperatures, reconstitution, and use of required 
processes (e.g. required diluents, administration sets). 
4.2.1 Cabiralizumab  
The investigational supply of cabiralizumab will be provided to the study centers by the Sponsor 
(or designee) and will be administered to patients in the clinical study by a trained healthcare 
professional.  
Cabiralizumab drug product is supplied for IV administration as a sterile, aqueous, colorless to 
pale yellow liquid, clear to slightly opalescent pyrogen-free solution in 5 mL glass vials 
stoppered with coated stoppers, and equipped with aluminum seals. Light (few) particulates 
(consistent in appearance to proteinaceous particles) may be present. Each vial contains a 
minimum of 5 mL of a 20 mg/mL solution of cabiralizumab (approximately 100 mg per vial). 
Storage Conditions: 2–8°C (36–46°F). The vials will be provided in a carton. Both vials and 
cartons will be labeled per local regulations. Refer to the pharmacy manual for more specific 
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treatment cohort. If any Grade 3 or higher infusion reaction is observed during the proposed 
infusion rate of nivolumab 3 mg/kg over 30 minutes, the infusion rate will be extended to 60 
minutes for all current and subsequent patients for the duration of this study.  
There will be no dose escalations or reductions of nivolumab allowed. Patients may be dosed no 
less than 12 days from the previous dose. There are no premedications recommended for 
nivolumab on the first cycle. Refer to the Pharmacy Manual for nivolumab preparation 
instructions.  
4.3.1.2 
Cabiralizumab Dosing 
For patients in the combination therapy cohorts, the cabiralizumab infusion will be administered 
30 minutes IV infusion, after the end of the nivolumab infusion and a 30- to 60-minute rest, on 
Day 1 of each 14 or 21day treatment cycle depending on treatment cohort. For patients in the 
monotherapy cohorts, the cabiralizumab infusion can be initiated at any time as a 30-minute IV 
infusion on Day 1 of each 14-day treatment cycle. 
Cabiralizumab dosing may be modified based on toxicities noted during the treatment period. If 
necessary, the dose will be adjusted 
 
) and Sections 4.3.2, 4.3.4, 4.3.5, and 4.3.10. 
A research pharmacist (or other responsible personnel) will prepare the solution for 
administration. After calculating the number of vials, based on the patient’s weight, the study 
drug product will be diluted with 0.9% Sodium Chloride Injection, USP. Prepared cabiralizumab 
should be administered within 6 hours after preparation (ambient temperature). The IV 
administration setup for cabiralizumab infusion must contain a 0.2 or 0.22 µm in-line filter or a 
0.2 or 0.22 µm syringe filter. Cabiralizumab will be administered under medical supervision as a 
30 minute (± 5 minutes) IV infusion via a peripheral vein or central venous catheter. No 
incompatibilities between cabiralizumab infusion and polyvinyl chloride (PVC), 
ethylene/propylene IV components, or glass bottles have been observed. 
4.3.2 Dose Delay for Cabiralizumab and Nivolumab  
Administration of cabiralizumab and/or nivolumab in combination therapy should be delayed for 
the following: 
• Any Grade 3 fatigue which does not resolve to Grade 1 or baseline before the next 
treatment visit 
• Any drug-related laboratory abnormalities would not require a dose delay unless 
clinically indicated or specified in the protocol or abnormal laboratory management table 
(Appendix H). Please discuss with the Sponsor’s Medical Monitor or designee as needed. 
 
 
 

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Patients who require a dose delay of cabiralizumab or cabiralizumab /nivolumab should be re-
evaluated weekly or more frequently if clinically indicated and resume study drug dosing when 
re-treatment criteria are met. 
If a patient experiences an infusion reaction to cabiralizumab, or nivolumab, or both study drugs, 
the infusion reaction should be treated following the infusion reaction treatment guidelines  
 
If the causality of the AE requiring a dose delay is confirmed to be due to one of the study drugs 
of the combination therapy, the non-offending drug may be continued per protocol taking into 
account the safety and clinical benefit to the patient.  
4.3.3 Criteria to Resume Treatment with Cabiralizumab and Nivolumab 
Patients may resume treatment with cabiralizumab and/or nivolumab when the drug-related AE 
resolves 
 
The Sponsor’s Medical Monitor or designee can be 
contacted at any time if further clarification is needed. 
4.3.4 Dose Reduction with Cabiralizumab and Nivolumab 
Dose reduction for cabiralizumab and nivolumab are not permitted.  
4.3.5 Dose Discontinuation Criteria for Cabiralizumab and Nivolumab 
Discontinuation rules may be different for monotherapy and combination therapy and not all 
rules will apply to both arms of the study. 
 
 
Treatment of cabiralizumab in monotherapy or cabiralizumab in combination with nivolumab 
should be discontinued in the following cases unless otherwise specified: 
• Any Grade 3 or higher uveitis or any Grade 2 drug-related uveitis, eye pain, or blurred 
vision that does not respond to topical therapy and does not improve to Grade 1 within 
the second re-treatment period or that requires systemic treatment  
• Any Grade 3 or higher infusion-related reactions and hypersensitivity requiring 
discontinuation. Any re-initiation of therapy in this circumstance would require 
consultation with the Sponsor’s Medical Monitor or designee. 
• Any Grade 3 non-skin, drug-related AE lasting >7 days, including drug-related uveitis, 
pneumonitis, hypoxia, bronchospasm, and endocrinopathies with the following 
exceptions: 
– Grade 3 drug-related endocrinopathies adequately controlled with only physiologic 
hormone replacement do not require discontinuation 
– Grade 3 drug-related laboratory abnormalities do not require treatment 

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discontinuation except: 
 Grade 3 drug-related thrombocytopenia >7 days or associated with Grade ≥2 
bleeding requires discontinuation 
• Any drug-related liver function test (LFT) abnormality that meets any one of the 
following criteria requires discontinuation: 
– ALT or AST >3x ULN and total bilirubin >2x ULN or INR > 1.5 xULN (in the 
absence of anticoagulation). 
 
 
– ALT or AST > 20x ULN (with or without concurrent liver metastases) 
– Total bilirubin >3x ULN (>5x ULN with concurrent liver metastases) 
• Any Grade 4 drug-related AE or laboratory abnormality, except for the following events 
which do not require discontinuation: 
– Grade 4 neutropenia <7 days 
– Grade 4 lymphopenia or leukopenia <7 days 
– Isolated Grade 4 amylase or lipase abnormalities that are not associated with 
symptoms or clinical manifestations of pancreatitis. The Sponsor’s Medical Monitor 
or designee should be consulted for Grade 4 amylase or lipase abnormalities. 
– Isolated Grade 4 electrolyte imbalances/abnormalities that are not associated with 
clinical sequelae and are corrected with supplementation/appropriate management 
within 72 hours of their onset 
– Grade 4 drug-related endocrinopathy AEs, such as adrenal insufficiency, 
adrenocorticotropic hormone (ACTH) deficiency, hyper- or hypothyroidism, or 
glucose intolerance, which resolve or are adequately controlled with physiologic 
hormone replacement (corticosteroids, thyroid hormones) or glucose-controlling 
agents, respectively, may not require discontinuation after discussion with and 
approval from the Sponsor’s Medical Monitor or designee.  
– Grade 4 CK up to 20 xULN (in the absence of clinical sequelae) 
• Any event that leads to delay in dosing lasting > 6 weeks from the previous dose requires 
discontinuation, with the following exceptions: 
– Dosing delays to manage drug-related adverse events are allowed. Prior to re-
initiating treatment in a patient with a dosing delay lasting > 6 weeks from the 
previous dose, the Sponsor’s Medical Monitor or designee must be consulted. Tumor 
assessments should continue as per-protocol even if dosing is delayed. Periodic study 
visits to assess safety and laboratory studies should also continue per protocol, or 
more frequently if clinically indicated during such dosing delays or per the 
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– Dosing delays lasting > 6 weeks from the previous dose that occur for non-drug-
related reasons may be allowed if approved by the Sponsor’s Medical Monitor or 
designee. Prior to re-initiating treatment in a patient with a dosing delay lasting > 6 
weeks, the Sponsor’s Medical Monitor must be consulted. Tumor assessments should 
continue per protocol every 8 weeks (±7 days) even if dosing is delayed. Periodic 
study visits to assess safety and laboratory studies should also continue per-protocol 
or more frequently if clinically indicated during such dosing delays or per the 
Investigator’s discretion. 
• Any AE, laboratory abnormality, or intercurrent illness which, in the opinion of the 
Investigator, presents a substantial clinical risk to the patient with continued 
cabiralizumab and/or nivolumab dosing 
• Any drug-related Grade 3 or higher neurological toxicity  
• Any Grade 3 or higher periorbital edema and persistent Grade 2 periorbital edema 
requiring 2 missed doses unless approved by Sponsor’s Medical Monitor 
• Any Grade 3 or higher drug-related diarrhea or colitis, which does not resolve to Grade 1 
or baseline within 28 days. 
• Any Grade 4 skin toxicity 
• Any Grade 4 renal toxicity 
• Any drug-related Grade 3 or higher pulmonary toxicity 
If the causality of the adverse event requiring discontinuation is confirmed to be due to one 
of the study drugs in the combination therapy, the other drug may be continued per protocol 
schedule under the following scenarios: 
• Timely resolution of the adverse event based on the treatment modification table 
• Clinical benefit is shown by the patient based on Investigator assessment 
4.3.6 Infusion Delays and Missed Doses with Cabiralizumab and Nivolumab 
In case an infusion cannot be administered at a scheduled visit, it must be administered as soon 
as possible. If the delay is between 1 and 7 days, the procedures at the original scheduled visit 
should be performed. If the delay is more than 7 days, the infusion at the original scheduled visit 
will be considered a missed dose and the procedures at the next visit should be performed. If the 
delay is longer than 7 days, subsequent visits will follow a 2-week (or 3-week in Phase 1a 3-
week dosing regimen cohort) dosing interval. If the delay is less than 7 days, the original dosing 
schedule should be followed. The time between two treatment cycles should be no less than 12 
days. 
Patients may miss up to up to 6 weeks between doses and may resume the study drug if the event 
returns to baseline or ≤ Grade 1 within 6 weeks of treatment interruption. Omission of additional 
dosing longer than 6 weeks for AEs will necessitate the patient’s discontinuation from the study 
unless allowed by the Sponsor’s Medical Monitor or designee. Patients may miss doses in the 

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course of participation in the study, including missed doses for scheduled vacations or other 
personal reasons as needed, but not more than 6 weeks unless approved by the Sponsor’s 
Medical Monitor or designee. 
4.3.7 Intra-Patient Dose Escalation with Cabiralizumab and Nivolumab 
Intra-patient dose escalation is not allowed for nivolumab or cabiralizumab. 
4.3.8 Treatment beyond Disease Progression with Cabiralizumab and Nivolumab 
Accumulating evidence indicates a minority of patients treated with immunotherapy may derive 
clinical benefit despite initial evidence of progressive disease 
 
Patients treated with cabiralizumab and nivolumab combination therapy will be permitted to 
continue cabiralizumab and nivolumab treatment beyond initial RECIST v1.1 defined 
progressive disease, assessed by the Investigator, as long as the following criteria are met: 
• Patients who will be treated beyond disease progression must review and sign an ICF 
before continuing on study drug 
• The patient demonstrates investigator-assessed clinical benefit, and do not have rapid 
disease progression 
• Tolerance of study drugs 
• Stable performance status 
• Treatment beyond progression will not delay an imminent intervention to prevent serious 
complications of disease progression (e.g., CNS metastases) 
A radiographic assessment/scan should be performed approximately 8 weeks (±7 days) after 
initial Investigator-assessed progression to determine whether there has been a decrease in the 
tumor size or continued progressive disease. The assessment of clinical benefit should be 
balanced by clinical judgment as to whether the patient is clinically deteriorating and unlikely to 
receive any benefit from continued treatment with cabiralizumab and nivolumab. 
If the Investigator feels that any patient receiving cabiralizumab and nivolumab will obtain 
clinical benefit by continuing treatment, the patient may remain on the trial and continue to 
receive monitoring according to the time and event schedules per protocol. 
For the patients who continue cabiralizumab and nivolumab study therapy beyond progression, 
further progression is defined as an additional 10% increase in tumor burden from time of initial 
progression. This includes an increase in the sum of diameters of all target lesions and/or the 
diameters of new measurable lesions compared to the time of initial progression. cabiralizumab 
and nivolumab treatment should be discontinued permanently upon documentation of further 
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4.3.9 Dose Modification Algorithms for Immuno-Oncology Agents 
Immuno-oncology agents are associated with AEs that can differ in severity and duration 
compared to AEs caused by other therapeutic classes. Cabiralizumab and nivolumab are 
considered immuno-oncology agents in this protocol. Early recognition and management of AEs 
associated with immuno-oncology agents may mitigate severe toxicity. Management algorithms 
have been developed to assist Investigators in assessing and managing the following classes of 
AEs: 
• Gastrointestinal 
• Renal 
• Pulmonary 
• Hepatic 
• Endocrinopathy 
• Skin 
• Neurological 
• Infusion reaction 
• Periorbital edema 
• Uveitis 
• Laboratory abnormalities 
 
  
4.3.10 Treatment of Cabiralizumab and Nivolumab-Related Infusion Reactions 
Cabiralizumab and nivolumab may induce infusion or hypersensitivity reactions. If such a 
reaction were to occur, it may manifest with fever, chills, rigors, headache, rash, pruritus, 
arthralgia, hypo- or hypertension, bronchospasm, or other symptoms. 
Infusion reactions should be graded according to CTCAE v4.03 guidelines. Any Grade 3 or 
Grade 4 infusion reaction should be reported within 24 hours to the Sponsor’s Medical Monitor 
or designee, and reported as an SAE if it meets the criteria.  
The nivolumab 30-minute infusion will be administered first, with a 30- to 60-minute rest, 
followed by the cabiralizumab 30-minute infusion. It may be unclear if an infusion reaction is 
due to cabiralizumab, nivolumab, or to both study drugs. Therefore, one set of treatment 
recommendations (based on the most conservative treatments for infusion reactions due to either 
study drug) is provided below and may be modified based on clinical judgment, local treatment 
standards and guidelines, and/or specific symptoms, as appropriate: 

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For Grade 1 symptoms: Mild reaction (e.g., localized cutaneous reactions including mild 
pruritus, flushing, rash), requires infusion rate to be decreased; intervention may be indicated. 
• Decrease the rate of the study drug infusion until recovery from symptoms. 
• Remain at bedside and monitor the patient’s vital signs until resolution of symptoms. 
Diphenhydramine 50 mg may be administered at the discretion of the treating physician. 
• When symptoms resolve, restart the infusion at the original infusion rate. 
• If a patient has an infusion reaction with nivolumab, cabiralizumab can be given (without 
prophylactic medications) if the infusion reaction resolves within 3 hours. For scheduling 
purposes, cabiralizumab infusion may be given the next day. Prophylactic pre-infusion 
medications should be given prior to all subsequent nivolumab infusions. 
• If a patient has an infusion reaction with cabiralizumab, prophylactic pre-infusion 
medications should be given prior to all subsequent cabiralizumab and nivolumab 
infusions. 
• The following prophylactic pre-infusion medications are recommended prior to future 
infusions of cabiralizumab and nivolumab: diphenhydramine 50 mg (or equivalent) 
and/or paracetamol (acetaminophen) 325 to 1000 mg at least 30 minutes before additional 
study drug administrations. 
For Grade 2 symptoms: Moderate reaction (i.e., any symptom not listed above [mild 
symptoms] or below [severe symptoms] such as generalized pruritus, flushing, rash, dyspnea, 
hypotension with systolic blood pressure >80 mmHg), requires infusion interruption but 
responds promptly to symptomatic treatment (e.g., antihistamines, nonsteroidal anti-
inflammatory drugs, narcotics, corticosteroids, IV fluids); prophylactic pre-infusion medications 
indicated for ≤24 hours. 
• Interrupt the study drug infusion. 
• Begin an IV infusion of normal saline, and treat the patient with diphenhydramine 50 mg 
IV (or equivalent) and/or paracetamol (acetaminophen) 325 to 1000 mg. 
• Remain at bedside and monitor the patient’s vital signs until resolution of symptoms. 
Corticosteroid therapy may be administered at the discretion of the treating physician. 
• When symptoms resolve, restart the infusion at 50% of the original infusion rate; if no 
further complications ensue after 30 minutes, the rate may be increased to 100% of the 
original infusion rate. 
• Monitor the patient closely. If symptoms recur, immediately discontinue the infusion; no 
further study drug will be administered at that visit. Administer diphenhydramine 50 mg 
IV, and remain at bedside and monitor the patient until resolution of symptoms. 
• If a patient has an infusion reaction with nivolumab infusion, cabiralizumab infusion can 
be given (without prophylactic medications) if the infusion reaction resolves within 3 
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Prophylactic pre-infusion medications should be given prior to all subsequent nivolumab 
infusions. 
• If a patient has an infusion reaction with cabiralizumab, prophylactic pre-infusion 
medications should be given prior to all subsequent cabiralizumab and nivolumab 
infusions. 
• The following prophylactic pre-infusion medications are recommended prior to future 
infusions of cabiralizumab and nivolumab: diphenhydramine 50 mg (or equivalent) 
and/or paracetamol (acetaminophen) 325 to 1000 mg should be administered at least 30 
minutes before additional study drug administrations. If necessary, corticosteroids (up to 
25 mg of SoluCortef or equivalent) may be used. 
• The amount of study drug infused must be recorded.  
For Grade 3 or Grade 4 symptoms: Severe reaction such as bronchospasm, generalized 
urticaria, systolic blood pressure <80 mmHg, or angioedema; Grade 3 symptoms including 
prolonged symptoms, which require 6 or more hours to respond to symptomatic medication 
and/or discontinuation of infusion; recurrence of symptoms following initial improvement; 
hospitalization indicated for other clinical sequelae, such as renal impairment, pulmonary 
infiltrates; Grade 4: life-threatening; pressor or ventilation support indicated. 
• Immediately discontinue the study drug infusion. No further study drug will be 
administered. The amount of study drug infused must be recorded on the CRF. 
• Begin an IV infusion of normal saline, and treat the patient as follows: Recommend 
bronchodilators, epinephrine 0.2 to 1.0 mg of a 1:1,000 solution for subcutaneous 
administration or 0.1 to 0.25 mg of a 1:10,000 solution injected slowly for IV 
administration, and/or diphenhydramine 50 mg IV with methylprednisolone 100 mg IV 
(or equivalent), as needed. 
• Remain at bedside and monitor the patient’s vital signs until recovery from symptoms. 
• The patient should be monitored until the Investigator is comfortable that the symptoms 
will not recur. 
• Investigators should follow their institutional guidelines for the treatment of anaphylaxis.  
In the case of late-occurring hypersensitivity symptoms (e.g., appearance of a localized or 
generalized pruritus within 1 week after treatment), symptomatic treatment may be given (e.g., 
oral antihistamine, or corticosteroids). 
4.4 
Method of Assigning Patient Identification  
Patients must be able to provide written informed consent and meet all eligibility criteria. No 
waivers of inclusion or exclusion criteria will be granted by Sponsor or its designee for any 
patient enrolled in the study. Before enrolling a patient, all eligibility criteria must be satisfied.  
Patients who qualify for Phase 1a dose esclation of the study will be enrolled as follows: 

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• The 2 mg/kg cabiralizumab monotherapy cohort was enrolled first, followed by 
enrollment to the 1mg/kg cabiralizumab /nivolumab combination cohort. Patients in these 
cohorts will be treated for a total of two 14-day treatment cycles within the DLT period. 
• Enrollment into the 4 mg/kg cabiralizumab monotherapy cohort will proceed once the 
DLT period is cleared in preceding monotherapy cohorts.  
• Dose escalation into increasing dose levels of cabiralizumab in combination with 
nivolumab may proceed until DLTs are observed either in the cabiralizumab 
monotherapy or the cabiralizumab in combination with nivolumab cohorts after 
discussion and agreement by the Cohort Review Committee. 
In 3-week dosing regimen Cohort (1aD), approximately 10 patients will be enrolled into the 4 
mg/kg cabiralizumab in combination with nivolumab cohort. These patients will receive study 
treatment every three weeks. 
The Phase 1a exploration consists of six cohorts of approximately 10 patients each. These 
cohorts are further evaluating the safety, PK, and PD of cabiralizumab as monotherapy and in 
combination with nivolumab. 
In Phase 1b, approximately 30 patients will be enrolled per cohort. Enrollment will be open for 
all cohorts in parallel and will continue until the enrollment target is reached. Once a cohort is 
filled, further enrollment will be restricted to the cohort(s) that have not been filled. A total of 
approximately 210 patients will be enrolled in the Phase 1b arm of the study. 
The Investigator may repeat qualifying lab tests and vitals/ECGs prior to enrollment if a non-
qualifying finding is considered an error or an acute finding is likely to meet eligibility criteria 
upon repeat testing. 
4.5 
Blinding/Unblinding 
This is an open-label study and there will be no blinding or unblinding of patients during this 
study. 
4.6 
Treatment Compliance 
Study drug will be administered by qualified trained site personnel in the clinical facility. The 
Investigator or their designated study personnel will maintain a log (Drug Accountability Log) of 
all study drugs received dispensed and destroyed. The Investigator and the study personnel will 
ensure that each patient receives the calculated dose of the study drug based on body weight. 
Drug supplies will be inventoried and accounted for throughout the study. The Drug 
Accountability Log will be reviewed by the study monitor during site visits and at the 
completion of the study. Any discrepancy should be brought to the attention of the Sponsor. 
Records of study medication administration (date, start and stop time, and dose administered 
relative to time of preparation) will be recorded on the patient’s CRF. 

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4.7 
Destruction of Study Drug 
Any unused study drugs can only be destroyed on site after being inspected and reconciled by the 
responsible site monitor unless study drug vials must be immediately destroyed as required for 
safety, or to meet local regulations (e.g., cytotoxics or biologics). 
• On-site destruction is allowed provided the following minimal standards are met: 
• On-site disposal practices must not expose humans to risks from the drug. 
• On-site disposal practices and procedures are in agreement with applicable laws and 
regulations, including any special requirements for controlled or hazardous substances. 
• Written procedures for on-site disposal are available and followed. The procedures must 
be filed with the site’s Standard Operating Procedures (SOPs) and a copy provided to the 
Sponsor upon request. 
• Records are maintained that allow for traceability of each vial, including the date 
disposed of, quantity disposed, and identification of the person disposing of the 
containers. The method of disposal (i.e., incinerator, licensed sanitary landfill, or licensed 
waste disposal vendor) must also be documented. 
• Accountability and disposal records are complete, up-to-date, and available for the Study 
Monitor to review throughout the clinical trial period. 
If conditions for destruction cannot be met, the responsible Study Monitor will make 
arrangements for return of study drug (Section 4.8). 
It is the Investigator’s responsibility to arrange for disposal of all empty containers, provided that 
procedures for proper disposal have been established according to applicable federal, state, local, 
and institutional guidelines and procedures and provided that appropriate records of disposal are 
kept. 
4.8 
Return of Study Drug 
If study drug will not be destroyed on site upon completion or termination of the study, all 
unused and/or partially used study drug that was supplied must be returned. The return of study 
drug will be arranged by the responsible Study Monitor. 

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5. 
Study Assessments and Procedures  
5.1 
Schedule of Assessments 
The schedule of assessment tables are attached to the protocol as Appendix A, Appendix B, and 
Appendix C. 
5.2 
Study Procedures by Visit 
5.2.1 Phase 1a Monotherapy 
5.2.1.1 
Screening Period (Day –28 to Day 0) 
Patients who have fully consented to participation in the study will undergo screening 
assessments within 28 days (4 weeks) prior to administration of the first infusion of 
cabiralizumab (unless otherwise stated). To determine if the patient meets all inclusion criteria 
and does not violate any exclusion criteria, the following procedures will be performed 
(Appendix A). 
• Written, signed informed consent must be collected prior to any study-specific 
procedures 
• If available, collect a formalin fixed, paraffin-embedded (FFPE) tissue block or 10 slides 
of archival tumor sample 
• Complete medical and disease history including prior HPV status 
• Demographic and baseline characteristics 
• Complete physical examination including height and weight 
• Photo of periorbital region (required at screening, and if clinically indicated during the 
study) 
• Vital signs (blood pressure, pulse, respiratory rate, and temperature in resting position 
after 5 minutes rest) 
• ECOG performance status evaluation  
• Screening labs (as described in Appendix A) 
• Clinical safety labs (as described in Appendix A) 
• Collect sample if the patient is being followed for a tumor marker (e.g. CA-125, or 
others) 
• 12-lead ECG (required at screening, and if clinically indicated during the study) 
• Radiological imaging: CT or MRI is to be performed within 28 days prior to Cycle 1 Day 
1. If the CT or MRI is performed as part of the patient’s standard of care within 28 days 
of Cycle 1 Day 1, it does not need to be repeated if the documentation of results is 
provided and is adequate for RECIST v1.1.  

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• Serum pregnancy test (β-hCG) for women of childbearing potential  
• Skin and tumor biopsy collection (at least 24 hours prior to dosing; analyses described in 
Appendix D) 
• SAE reporting, if applicable 
• Document prior and concomitant medications 
5.2.1.2 
Cycle 1, Day 1  
The following procedures will be performed: 
• Prior to cabiralizumab infusion (within ≤72 hours unless otherwise stated): 
– Verification of eligibility 
– Update medical and disease history to capture any changes from screening 
– Physical examination including weight 
– Vital signs (blood pressure, pulse, respiratory rate and temperature in resting position 
after 5 minutes rest) 
– ECOG performance status evaluationClinical safety labs (as described in 
Appendix A; results must be reviewed before dosing) 
– Collect sample if the patient is being followed for a tumor marker (e.g. CA-125 or 
others) 
– Serum pregnancy test (β-hCG) for women of childbearing potential 
– Blood collection for: 
 Serum (analyses described in Appendix D, excluding all nivolumab analyses) 
 Whole blood (analyses described in Appendix D) 
 Frozen PBMC (analyses described in Appendix D) 
– AE reporting, if applicable 
– Review of concomitant medications 
• Study drug administration: cabiralizumab by IV infusion over 30 minutes (± 5 minutes) 
‒ Post cabiralizumab administration: 
 Post-dose vital signs (heart rate, blood pressure, respiratory rate, and temperature 
in resting position after 5 minutes rest) at the following time points after 
completion of the IV infusion: 
– 10 (±5) minutes, 30 (±10) minutes, and 60 (±15) minutes 
– Blood collection for serum cabiralizumab PK 
▪ 
15 (±5) minutes post-dose 
– Blood collection for serum cabiralizumab PK 
▪ 
4 hours (± 60 minutes) post-dose 

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5.2.1.3 
Cycle 1, Day 2 
Patients will return to the study center on Day 2 for 24-hour (± 6 hours) post-dose assessments. 
No treatment will be administered during this visit, but the following assessments will be 
completed: 
• Blood collection for: 
– Serum (cabiralizumab PK) 
• AE reporting, if applicable 
• Review of concomitant medications 
5.2.1.4 
Cycle 1, Day 4 
Patients will return to the study center on Day 4 for 72-hour (± 12 hours) post-dose assessments. 
No treatment will be administered during this visit, but the following assessments will be 
completed: 
• Blood collection for: 
– Serum (cabiralizumab PK) 
– Whole blood (gene expression analyses only) 
• AE reporting, if applicable 
• Review of concomitant medications 
5.2.1.5 
Cycle 1, Day 8 
Patients will return to the study center on Day 8 for 168-hour (± 24 hours) post-dose 
assessments. No treatment will be administered during this visit, but the following assessments 
will be completed: 
• Physical examination 
• Vital signs (blood pressure, pulse, respiratory rate, and temperature in resting position 
after 5 minutes rest) 
• Clinical safety labs (as described in Appendix A) 
• Blood collection for: 
– Serum (cabiralizumab PK) 
– Whole blood (analyses described in Appendix D) 
– Frozen PBMC (analyses described in Appendix D) 
• AE reporting, if applicable 
• Review of concomitant medications  

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5.2.1.6 
Cycle 2, Day 1 
The following procedures will be performed (a ± 2 day window is allowed for Day 1 in 
subsequent cycles post Cycle 1, Day 1): 
• Prior to cabiralizumab infusion (within ≤ 72 hours unless otherwise stated): 
– Physical examination including weight 
– Vital signs (blood pressure, pulse, respiratory rate, and temperature in resting position 
after 5 minutes rest) 
– ECOG performance status evaluation  
– Clinical safety labs (as described in Appendix A; results must be reviewed before 
dosing)  
– Blood collection for: 
 Serum (analyses described in Appendix D, excluding all nivolumab analyses) 
 Whole blood (analyses described in Appendix D)  
 Frozen PBMC (analyses described in Appendix D) 
– AE reporting, if applicable 
– Review of concomitant medications 
• Study drug administration: cabiralizumab by IV infusion over 30 minutes (± 5 minutes) 
– Post cabiralizumab administration: 
 Post-dose vital signs (blood pressure, pulse, respiratory rate, and temperature in 
resting position after 5 minutes rest) at the following time points after completion 
of the IV infusion: 
– 10 (±5) minutes, 30 (±10) minutes, and 60 (±15) minutes 
 15 (±5) minutes post-dose 
– Blood collection for serum (cabiralizumab PK) 
5.2.1.7 
End of the DLT Period (Phase 1a Dose Escalation cohorts only) 
For Phase 1a patients in monotherapy dose escalation cohort, if at the end of the DLT period, the 
Investigator determines that the patient may benefit from continued dosing with cabiralizumab, 
entry into the Extended Treatment Period may be offered.  
If the patient is continuing onto the Extended Treatment Period, proceed to procedures outlined 
in Section 5.2.1.8. 
If the patient does not qualify to receive further doses of cabiralizumab, the patient will return to 
the clinic for the End-of-Treatment Visits outlined in Section 5.2.1.9.  

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5.2.1.8 
Extended Treatment – Subsequent Cycles, Day 1 
Phase 1a extended treatment for patients in monotherapy cohorts (1aM) may begin upon 
completion of the DLT period. Dosing will be discontinued if the patient experiences either 
disease progression or unacceptable toxicity.  
At each infusion visit, patients are to remain at the study site after each administration of 
cabiralizumab until completion of all post-dose assessments for safety monitoring. The following 
assessments will be performed at each visit unless otherwise noted (Appendix A) (a ± 2 day 
window is allowed for Day 1 in subsequent cycles post Cycle 1, Day 1): 
• Prior to each infusion of study drug (within 72 hours unless otherwise stated):  
– Physical examination including weight 
– Vital signs (blood pressure, pulse, respiratory rate, and temperature in resting position 
after 5 minutes rest) 
– ECOG performance status evaluation 
– Clinical safety labs (as described in Appendix A; results must be reviewed before 
dosing) 
– Collect sample if the patient is being followed for a tumor marker (e.g. CA-125, or 
others) on Cycle 3 Day 1, then every other cycle after, or as clinically indicated 
– Radiological imaging: CT or MRI scan performed every 8 weeks (± 7 days) from the 
first dose for the first 12 months for patients who remain on treatment (and every 12 
weeks (± 7 days) thereafter) and 28 days (± 7 days) after the last dose of study 
treatment.  
– Serum pregnancy test (β-hCG) for women of childbearing potential on Cycle 5, Day 
1, then every 8 weeks (every 4 cycles) 
– Skin and tumor biopsy collection (prior to Cycle 3 only, within 7 days prior to Cycle 
3 Day 1 and at least 24 hour prior to dosing; for analyses described in Appendix D) 
– Optional skin and tumor biopsy for patients who responded to treatment (within 
14 days post tumor assessment; for analyses described in Appendix D) 
– Blood collection for: 
 Serum (for analyses described in Appendix D) as listed below. 
– Cabiralizumab PK for Cycles 3, 4, 5, 8, 9, 13, and 21, then every 6 cycles 
while on treatment 
– Cabiralizumab ADA for Cycles 3, 4, 5, 9, 13, and 21, then every 6 cycles 
while on treatment 
– ANA for Cycles 3, 4, 5, 9, 13, 21, then every 6 cycles while on treatment 
– Selected serum markers for Cycles 3, 4, 5, 8, 9, 13, and 21 

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– Cytokine multiplex panel for Cycles 3, 4, 5, 8, 9, 13, and 21  
 Whole blood (for analyses described in Appendix D) as listed below. 
– CD14+/CD16+ monocytes for Cycles 3, 4, 5, 8, and 9, 13, and 21, then every 
6 cycles while on treatment  
– Gene expression analysis for Cycle 3, 5, 9, 13, and 21, then every 6 cycles 
while on treatment  
– Frozen PBMC for Cycle 3 (analyses described in Appendix D)  
– AE reporting, if applicable 
– Review of concomitant medications 
• Study drug administration: cabiralizumab by IV infusion over 30 minutes (± 5 minutes) 
• Post cabiralizumab administration: 
– Post-dose vital signs (blood pressure, pulse, respiratory rate, and temperature in 
resting position after 5 minutes rest) at the following time points after completion of 
the IV infusion: 
 10 (±5) minutes, 30 (±10) minutes, and 60 (±15) minutes 
 Blood collection for serum (for analyses described in Appendix D) as listed 
below. 
 Cabiralizumab PK 15 minutes (±5 minutes) for Cycles 3 and 4 
 Cabiralizumab PK 15 minutes (±5 minutes), 4 hours (±60 minutes), 24 hours (±6 
hours), 72 hours (±12 hours) and 168 hours (±24 hours) for Cycle 8 only 
 Selected serum markers 72 hours (±12 hours) and 168 hours (± 24 hours) for  
Cycle 8 only 
 Cytokine multiplex panel 72 hours (±12 hours) and 168 hours (±24 hours) for 
Cycle 8 only  
 CD14+/CD16+ monocytes 72 hours (±12 hours) and 168 hours (±24 hours) for  
Cycle 8 only 
5.2.1.9 
End-of-Treatment Follow-up Period 
Patients will return to the study center twice, approximately 28 (± 7) days, followed by a 
subsequent visit 100 (±7) days after their last infusion of cabiralizumab, to complete the End-of-
Treatment Follow-up Period.  
The following assessments will be performed: 
• Physical examination including weight 
• Vital signs (blood pressure, pulse, respiratory rate, and temperature in resting position 
after 5 minutes rest) 
• ECOG performance status evaluation 

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• Clinical safety labs (as described in Appendix A) 
• 12-lead ECG (28 [±7] days, post last infusion of cabiralizumab visit only). 
• Radiological imaging: CT or MRI scan does not need to be repeated if performed within 
8 weeks prior to the End-of-Treatment Visits or if tumor progression was previously 
determined. 
• Serum pregnancy test (β-hCG) for women of childbearing potential  
• Optional skin and tumor biopsy for patients who progressed, (28 [±7] days, post last 
infusion of cabiralizumab visit only) (for analyses described in Appendix D) 
• Blood collection 
– Serum (analyses described in Appendix D, excluding all nivolumab analyses) 
– Whole blood (CD14+/CD16+ monocyte analysis and gene expression analysis only) 
• AE reporting, if applicable, until 100 (±7) days after the last dose of study drug or until 
initiation of subsequent anti-cancer therapy. Patients with ongoing SAEs will be followed 
until resolution or stabilization. 
• Review of concomitant medications 
5.2.2 Phase 1a Combination (including 1aC, 1aE, and 1aD cohorts)  
5.2.2.1 
Screening Period (Day –28 to Day 0) 
Patients who have consented to participation in the study will undergo screening assessments 
within 28 days (4 weeks) prior to administration of the first infusion of cabiralizumab and 
nivolumab (unless otherwise stated). To determine if the patient meets all inclusion criteria and 
does not violate any exclusion criteria, the following procedures will be performed 
(Appendix B): 
• Written, signed informed consent must be collected prior to any study-specific 
procedures 
• If available, collect an FFPE tissue block or 10 slides of archival tumor sample 
• Complete medical and disease history including prior HPV status 
• Demographic and baseline characteristics 
• Complete physical examination including height and weight 
• Photo of periorbital region (required at screening, and if clinically indicated during the 
study) 
• Vital signs (blood pressure, pulse, respiratory rate, pulse oximetry and temperature in 
resting position after 5 minutes rest) 
• ECOG performance status evaluation  

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• Screening labs (as described in Appendix B) 
• Clinical safety labs (as described in Appendix B) 
• Collect sample if the patient is being followed for a tumor marker (e.g. CA-125, or 
others) 
• 12-lead ECG (required at screening, and if clinically indicated during the study) 
• Radiological imaging: CT or MRI is to be performed within 28 days prior to Cycle 1 Day 
1. If the CT or MRI is performed as part of the patient’s standard of care within 28 days 
of Cycle 1 Day 1, it does not need to be repeated if the documentation of results is 
provided and is adequate for RECIST v1.1  
• Serum pregnancy test (β-hCG) for women of childbearing potential  
• Skin and tumor biopsy collection (at least 24 hour prior to dosing; analyses described in 
Appendix D) 
• SAE reporting, if applicable 
• Document prior and concomitant medications 
5.2.2.2 
Cycle 1, Day 1  
The following procedures will be performed: 
• Prior to cabiralizumab and nivolumab infusion (within 72 hours unless otherwise stated): 
– Verification of eligibility 
– Update medical and disease history to capture any changes from screening 
– Physical examination including weight 
– Vital signs (blood pressure, pulse, respiratory rate, pulse oximetry and temperature in 
resting position after 5 minutes rest) 
– ECOG performance status evaluation 
– Clinical safety labs (as described in Appendix B; results must be reviewed before 
dosing) 
– Collect sample if the patient is being followed for a tumor marker (e.g. CA-125, or 
others) 
– Serum pregnancy test (β-hCG) for women of childbearing potential  
– Blood collection for: 
 Serum (analyses described in Appendix D) 
 Whole blood (analyses described in Appendix D) 
 Frozen PBMC ( analyses described in Appendix D) 
– AE reporting, if applicable 

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– Review of concomitant medications 
• Study drug administration: Nivolumab will be given first, with a 30-minute rest, followed 
by cabiralizumab. 
– Nivolumab administered by IV infusion over 30 minutes (± 5 minutes) (If any Grade 
3 or higher infusion reaction is observed during the proposed infusion rate of 
nivolumab 3 mg/kg over 30 minutes, the infusion rate will be extended to 60 minutes 
for all current and subsequent patients for the duration of this study.) 
 Post-nivolumab administration: 
– Post-dose vital signs (blood pressure, pulse, respiratory rate, and temperature 
in resting position after 5 minutes rest) at the following time point after 
completion of each IV infusion: 
▪ 
10 (±5) minutes  
– Blood collection for serum nivolumab PK 
▪ 
15 (±5) minutes  
– Cabiralizumab administered by 30 minutes IV infusion (± 5 minutes) 
 Post- cabiralizumab administration: 
– Post-dose vital signs (blood pressure, pulse, respiratory rate, and temperature 
in resting position after 5 minutes rest) at the following time points after 
completion of cabiralizumab IV infusion: 
▪ 
10 (±5) minutes, 30 (±10) minutes, and 60 (±15) minutes 
– Blood collection for serum cabiralizumab PK 
▪ 
15 (±5) minutes  
▪ 
4 hours (± 60 minutes)  
5.2.2.3 
Cycle 1, Day 2 
Patients will return to the study center on Day 2 for 24-hour (± 6 hours) post-dose assessments. 
No treatment will be administered during this visit, but the following assessments will be 
completed: 
• Blood collection for: 
– Serum (cabiralizumab PK) 
• AE reporting, if applicable 
• Review of concomitant medications 
5.2.2.4 
Cycle 1, Day 4 
Patients will return to the study center on Day 4 for 72-hour (± 12 hours) post-dose assessments. 
No treatment will be administered during this visit, but the following assessments will be 
completed: 

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• Blood collection for: 
– Serum (cabiralizumab PK only) 
– Whole blood (CD14+/CD16+ monocyte and gene expression analyses)  
 CD14+/CD16+ monocyte analysis only for patients in Cohort 1aC1 (1 mg/kg 
cabiralizumab with 3 mg/kg nivolumab) 
• AE reporting, if applicable 
• Review of concomitant medications 
5.2.2.5 
Cycle 1, Day 8 
Patients will return to the study center on Day 8 for 168-hour (± 24 hours) post-dose 
assessments. No treatment will be administered during this visit, but the following assessments 
will be completed: 
• Physical examination 
• Vital signs (blood pressure, pulse, respiratory rate, pulse oximetry and temperature in 
resting position after 5 minutes rest) 
• Clinical safety labs (as described in Appendix B) 
• Blood collection for:  
– Serum (cabiralizumab PK) 
– Whole blood (CD14+/CD16+ monocyte and gene expression analyses) 
– Frozen PBMC (analyses described in Appendix D) 
• AE reporting, if applicable 
• Review of concomitant medications  
5.2.2.6 
Cycle 1, Day 15 (Cohort 1aD only) 
Patients will return to the study center on Day 15 for 336-hour (± 24 hours) post-dose 
assessments. No treatment will be administered during this visit, but the following procedures 
will be performed: 
• Physical examination 
• Vital signs (blood pressure, pulse, respiratory rate, pulse oximetry and temperature in 
resting position after 5 minutes rest) 
• Clinical safety labs (as described in Appendix B) 
• Blood collection for:  
– Serum (cabiralizumab PK) 

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• AE reporting, if applicable 
• Review of concomitant medications  
5.2.2.7 
Cycle 2, Day 1 
The following procedures will be performed (a ± 2 day window is allowed for Day 1 in 
subsequent cycles post Cycle 1, Day 1): 
• Prior to cabiralizumab and nivolumab infusion (within ≤72 hours unless otherwise 
stated): 
– Physical examination including weight 
– Vital signs (blood pressure, pulse, respiratory rate, pulse oximetry and temperature in 
resting position after 5 minutes rest) 
– ECOG performance status evaluation 
– Clinical safety labs (as described in Appendix B; results must be reviewed before 
dosing) 
– Blood collection for: 
 Serum (analyses described in Appendix D) 
 Whole blood (analyses described in Appendix D) 
 Frozen PBMC (analyses described in Appendix D) 
– AE reporting, if applicable 
– Review of concomitant medications 
• Study drug administration: Nivolumab will be given first, with a 30-minute rest, followed 
by cabiralizumab. 
– Nivolumab administered by IV infusion over 30 minutes (± 5 minutes) (If any Grade 
3 or higher infusion reaction is observed during the proposed infusion rate of 
nivolumab 3 mg/kg over 30 minutes, the infusion rate will be extended to 60 minutes 
for all current and subsequent patients for the duration of this study)  
 Post-nivolumab administration during the 30-minute rest: 
– Post-dose vital signs (blood pressure, pulse, respiratory rate, and temperature 
in resting position after 5 minutes rest) at the following time point after 
completion of each IV infusion: 
 10 (±5) minutes  
– Cabiralizumab administered by 30 minutes IV infusion (± 5 minutes) 
 Post- cabiralizumab administration: 
– Post-dose vital signs (blood pressure, pulse, respiratory rate, and temperature 
in resting position after 5 minutes rest) at the following time points after 
completion of cabiralizumab IV infusion: 

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▪ 
10 (±5) minutes, 30 (±10) minutes, and 60 (±15) minutes 
– Blood collection for serum cabiralizumab PK 
▪ 
15 (±5) minutes 
 
5.2.2.8 
End of DLT Period (Phase 1a Dose Escalation cohorts only) 
For Phase 1a patients in the combination dose escalation cohorts, if at the end of the DLT period 
the Investigator determines that the patient may benefit from continued dosing with 
cabiralizumab and nivolumab, entry into the Extended Treatment Period may be offered.  
If the patient continues onto the Extended Treatment Period, proceed to procedures outlined in 
Section 5.2.2.9. 
If the patient does not qualify to receive further study drug, the patient will return to the clinic for 
the End-of-Treatment Visits outlined in Section 5.2.2.11.  
5.2.2.9 
Extended Treatment – Subsequent Cycles, Day 1 
Phase 1a extended treatment for patients in combination dose escalation cohorts may begin on 
Cycle 3, Day 1.  
At each infusion visit, patients are to remain at the study site after each administration of 
cabiralizumab and nivolumab until completion of all post-dose assessments for safety 
monitoring. The following assessments will be performed at each visit unless otherwise noted 
(Appendix B) (a ± 2 day window is allowed for Day 1 in subsequent cycles post Cycle 1, Day 1): 
• Prior to each infusion of study drug (within 72 hours unless otherwise stated):  
– Physical examination including weight 
– Vital signs (blood pressure, pulse, respiratory rate, pulse oximetry and temperature in 
resting position after 5 minutes rest) 
– ECOG performance status evaluation 
– Clinical safety labs (as described in Appendix B; results must be reviewed before 
dosing) 
– Collect sample if the patient is being followed for a tumor marker (e.g. CA-125, or 
others) on Cycle 3 Day 1, then every other cycle after, or as clinically indicated  
– Radiological imaging: CT or MRI scan performed every 8 weeks (± 7 days) from the 
first dose for the first 12 months for patients who remain on treatment (and every 12 
weeks (± 7 days) thereafter) and 28 days (±7 days) after the last dose of study 
treatment.  
– Serum pregnancy test (β-hCG) for women of childbearing potential on Cycle 5, Day 
1, then every 8 weeks (every 4 cycles) 
– Skin and tumor biopsy collection (prior to Cycle 3 only; within 7 days prior to Cycle 

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3 Day 1 and at least 24 hours prior to dosing; analyses described in Appendix D) 
– Optional skin and tumor biopsy for patients who responded to treatment (within 14 
days post tumor assessment; for analyses described in Appendix D) 
– Blood collection for: 
 Serum (analyses described in Appendix D) as listed below. 
– Cabiralizumab PK for Cycles 3, 4, 5, 8, 9, 13, and 21, then every 6 cycles 
while on treatment  
– Nivolumab PK for Cycles 3, 4, 5, 8, 9, 13, and 21 
– Cabiralizumab ADA for Cycles 3, 4, 5, 8, 9, 13, and 21, then every 6 cycles 
while on treatment  
– Nivolumab ADA for Cycles 3, 4, 5, 8, 9, 13, and 21 
– ANA for Cycles 3, 4, 5, 9, 13, and 21, then every 6 cycles while on treatment 
– Selected serum markers for Cycles 3, 4, 5, 8, 9, 13, and 21 
– Cytokine multiplex panel for Cycles 3, 4, 5, 8, 9, 13, and 21  
 Whole blood (for analyses described in Appendix D) as listed below. 
– CD14+/CD16+ monocytes for Cycles 3, 4, 5, 8, 9, 13, and 21, then every 6 
cycles while on treatment 
– Gene expression analysis for Cycles 3, 5, 9, 13, 17, and 21, then every 6 
cycles thereafter 
– Frozen PBMC for Cycle 3 (analyses described in Appendix D) 
– AE reporting, if applicable 
– Review of concomitant medications 
• Study drug administration: Nivolumab will be given first, with a 30- to 60-minute rest, 
followed by cabiralizumab. 
– Nivolumab administered by IV infusion over 30 minutes (± 5 minutes) (If any Grade 
3 or higher infusion reaction is observed during the proposed infusion rate of 
nivolumab 3 mg/kg over 30 minutes, the infusion rate will be extended to 60 minutes 
for all current and subsequent patients for the duration of this study) 
 Post-nivolumab administration during the 30- to 60-minute rest: 
– Post-dose vital signs (blood pressure, pulse, respiratory rate, and temperature 
in resting position after 5 minutes rest) at the following time point after 
completion of each IV infusion: 
 10 (±5) minutes 
– Blood collection for serum (for analyses described in Appendix D) as listed 
below. 
 
15 minutes (±5 minutes) Nivolumab PK for Cycle 8 only  

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– Cabiralizumab administered by 30 minutes IV infusion (± 5 minutes) 
 Post- cabiralizumab administration: 
– Post-dose vital signs (blood pressure, pulse, respiratory rate, and temperature 
in resting position after 5 minutes rest) at the following time points after 
completion of cabiralizumab IV infusion: 
 
10 (±5) minutes, 30 (±10) minutes, and 60 (±15) minutes 
– Blood collection for serum (for analyses described in Appendix D) as listed 
below. 
 Cabiralizumab PK 15 minutes (±5 minutes) for Cycles 3 and 4 
 Cabiralizumab PK 15 minutes (±5 minutes), 4 hours (±60 minutes), 24 
hours (±6 hours), 72 hours (±12 hours) and 168 hours (±24 hours) for 
Cycle 8 only 
 Selected serum markers 72 hours (±12 hours) and 168 hours (± 24 hours) 
for Cycle 8 only 
 Cytokine multiplex panel 72 hours (±12 hours) and 168 hours (±24 hours) 
for Cycle 8 only  
 CD14+/CD16+ monocytes 72 hours (±12 hours) and 168 hours (±24 hours) 
for Cycle 8 only 
5.2.2.10 
Cycle 8, Day 15 (Cohort 1aD only) 
Patients will return to the study center on Day 15 for 336-hour (± 24 hours) post-dose 
assessments. No treatment will be administered during this visit, but the following procedures 
will be performed: 
• Physical examination 
• Vital signs (blood pressure, pulse, respiratory rate, pulse oximetry and temperature in 
resting position after 5 minutes rest) 
• Clinical safety labs (as described in Appendix B) 
• Blood collection for:  
– Serum (cabiralizumab PK) 
• AE reporting, if applicable 
• Review of concomitant medications  

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5.2.2.11 
End-of-Treatment Follow-up Period 
Patients will return to the study center twice, approximately 28 (±7) days, followed by a 
subsequent visit 100 (±7) days after their last infusion of cabiralizumab and nivolumab, to 
complete the End-of Treatment Follow-up Period.  
The following assessments will be performed: 
• Physical examination including weight 
• Vital signs (blood pressure, pulse, respiratory rate, pulse oximetry and temperature in 
resting position after 5 minutes rest) 
• ECOG performance status evaluation 
• Clinical safety labs (as described in Appendix B) 
• 12-lead ECG (28 [±7] days post last infusion of cabiralizumab and nivolumab visit only) 
• Radiological imaging: CT or MRI scan does not need to be repeated if performed within 
8 weeks prior to the End-of-Treatment Visits or if tumor progression was previously 
determined. 
• Serum pregnancy test (β-hCG) for women of childbearing potential 
• Optional skin and tumor biopsy for patients who progressed (28 [±7] days post last 
infusion of cabiralizumab and nivolumab visit only) (for analyses described in 
Appendix D) 
• Blood collection for: 
– Serum (analyses described in Appendix D) 
– Whole blood (CD14+/CD16+ monocyte analysis and gene expression analysis) 
• AE reporting, if applicable, until 100 (±7) days after the last dose of study drug or until 
initiation of subsequent anti-cancer therapy. Patients with ongoing SAEs will be followed 
until resolution or stabilization. 
• Review of concomitant medications 
5.2.3 Phase 1b Combination Dose Expansion 
5.2.3.1 
Screening Period (Day –28 to Day 0) 
Patients who have fully consented to participation in the study will undergo screening 
assessments within 28 days (4 weeks) prior to administration of the first infusion of 
cabiralizumab and nivolumab (unless otherwise stated). To determine if the patient meets all 
inclusion criteria and does not violate any exclusion criteria, the following procedures will be 
performed (Appendix B): 
• Written, signed informed consent must be collected prior to any study-specific 
procedures 

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• If available, collect an FFPE tissue block or 10 slides of archival tumor sample 
• Complete medical and disease history including prior HPV status 
• Demographic and baseline characteristics 
• Complete physical examination including height and weight 
• Vital signs (blood pressure, pulse, respiratory rate, pulse oximetry and temperature in 
resting position after 5 minutes rest;) 
• ECOG performance status evaluation  
• Screening labs (as described in Appendix B) 
• Clinical safety labs (as described in Appendix B) 
• Collect sample if the patient is being followed for a tumor marker (e.g. CA-125, or 
others) 
– CA-125 is required for cohort 1b5  
• 12-lead ECG (required at screening, and if clinically indicated during the study) 
• Radiological imaging: CT or MRI to be performed within 28 days prior to Cycle 1 Day 1. 
If the MRI is performed as part of the patient’s standard of care within 28 days of Cycle 1 
Day 1, it does not need to be repeated if documentation of the results is provided and is 
adequate for RECIST v 1.1.  
• Serum pregnancy test (β-HCG) for women of childbearing potential  
• Optional tumor biopsy collection (at least 24 hours prior to dosing; analyses described in 
Appendix D) 
• SAE reporting, if applicable 
• Document prior and concomitant medications 
5.2.3.2 
Cycle 1, Day 1  
The following procedures will be performed: 
• Prior to cabiralizumab and nivolumab infusion (within 72 hours unless otherwise stated): 
– Verification of eligibility 
– Update medical and disease history to capture any changes from screening 
– Physical examination including weight 
– Vital signs (blood pressure, pulse, respiratory rate, pulse oximetry and temperature in 
resting position after 5 minutes rest) 
– ECOG performance status evaluation 

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– Clinical safety labs (as described in Appendix B; results must be reviewed before 
dosing) 
– Collect sample if the patient is being followed for a tumor marker (e.g. CA-125, or 
others) 
 
CA-125 is required for cohort 1b5 
– Serum pregnancy test (β-hCG) for women of childbearing potential 
– Blood collection for: 
 
Serum (analyses described in Appendix D) 
 
Whole blood (analyses described in Appendix D) 
 
Frozen PBMC (analyses described in Appendix D) 
– AE reporting, if applicable 
– Review of concomitant medications 
• Study drug administration: Nivolumab will be given first, with a 30- to 60-minute rest, 
followed by cabiralizumab. 
– Nivolumab administered by IV infusion over 30 minutes (± 5 minutes) (If any Grade 
3 or higher infusion reaction is observed during the proposed infusion rate of 
nivolumab 3 mg/kg over 30 minutes, the infusion rate will be extended to 60 minutes 
for all current and subsequent patients for the duration of this study)  
 Post-nivolumab administration: 
– Post-dose vital signs (blood pressure, pulse, respiratory rate, and temperature 
in resting position after 5 minutes rest) at the following time point after 
completion of each IV infusion: 
 10 (±5) minutes  
– Blood collection for serum nivolumab PK 
 15 minutes (± 5 minutes)  
– Cabiralizumab administered by 30 minutes IV infusion (± 5 minutes) 
 Post- cabiralizumab administration: 
– Post-dose vital signs (blood pressure, pulse, respiratory rate, and temperature 
in resting position after 5 minutes rest) at the following time points after 
completion of cabiralizumab IV infusion: 
 10 (±5) minutes, 30 (±10) minutes, and 60 (±15) minutes 
– Blood collection for serum cabiralizumab PK 
 15 minutes (± 5 minutes) 
 4 hours (± 60 minutes) 

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5.2.3.3 
Cycle 1, Day 2 
Patients will return to the study center on Day 2 for 24-hour (± 6 hours) post-dose assessments. 
No treatment will be administered during this visit, but the following assessments will be 
completed: 
• Blood collection for: 
– Serum (cabiralizumab PK) 
• AE reporting, if applicable 
• Review of concomitant medications 
5.2.3.4 
Cycle 1, Day 4 
Patients will return to the study center on Day 4 for 72-hour (± 12 hours) post-dose assessments. 
No treatment will be administered during this visit, but the following assessments will be 
completed: 
• Blood collection for: 
– Serum (cabiralizumab PK only) 
– Whole blood (gene expression analyses only) 
• AE reporting, if applicable 
• Review of concomitant medications 
5.2.3.5 
Cycle 1, Day 8 
Patients will return to the study center on Day 8 for 168-hour (± 24 hours) post-dose 
assessments. No treatment will be administered during this visit, but the following assessments 
will be completed: 
• Physical examination 
• Vital signs (blood pressure, pulse, respiratory rate, pulse oximetry and temperature in 
resting position after 5 minutes rest;) 
• Clinical safety labs (as described in Appendix B) 
• Blood collection for: 
– Serum (cabiralizumab PK) 
– Whole blood (CD14+/CD16+ monocyte and gene expression analyses) 
– Frozen PBMC (analyses described in Appendix D) 
• AE reporting, if applicable 
• Review of concomitant medications  

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5.2.3.6 
Cycle 2, Day 1  
The following procedures will be performed (a ± 2 day window is allowed for Day 1 in 
subsequent cycles post Cycle 1, Day 1): 
• Prior to cabiralizumab and nivolumab infusion (within ≤72 hours unless otherwise 
stated): 
– Physical examination including weight 
– Vital signs (blood pressure, pulse, respiratory rate, pulse oximetry and temperature in 
resting position after 5 minutes rest) 
– ECOG performance status evaluation 
– Clinical safety labs (as described in Appendix B; results must be reviewed before 
dosing) 
– Blood collection for: 
 Serum (analyses described in Appendix D) 
 Whole blood (analyses described in Appendix D) 
 Frozen PBMC (analyses described in Appendix D) 
– AE reporting, if applicable 
– Review of concomitant medications 
• Study drug administration: Nivolumab will be given first, with a 30- to 60-minute rest, 
followed by cabiralizumab. 
– Nivolumab administered by IV infusion over 30 minutes (± 5 minutes) (If any Grade 
3 or higher infusion reaction is observed during the proposed infusion rate of 
nivolumab 3 mg/kg over 30 minutes, the infusion rate will be extended to 60 minutes 
for all current and subsequent patients for the duration of this study) 
 Post-nivolumab administration during the 30- to 60-minute rest: 
– Post-dose vital signs (blood pressure, pulse, respiratory rate, and temperature 
in resting position after 5 minutes rest) at the following time point after 
completion of each IV infusion: 
 10 (±5) minutes  
– Cabiralizumab administered by 30 minutes IV infusion (± 5 minutes) 
 Post- cabiralizumab administration: 
– Post-dose vital signs (blood pressure, pulse, respiratory rate, and temperature 
in resting position after 5 minutes rest) at the following time points after 
completion of cabiralizumab IV infusion: 
 10 (±5) minutes, 30 (±10) minutes, and 60 (±15) minutes 

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– Blood collection for serum cabiralizumab PK 
 15 minutes (± 5 minutes) 
5.2.3.7 
Cycle 3 and Subsequent Cycles, Day 1 
At each infusion visit, patients are to remain at the study site after each administration of 
cabiralizumab and nivolumab until completion of all post-dose assessments for safety 
monitoring. The following assessments will be performed at each visit unless otherwise noted 
(Appendix B) (a ± 2 day window is allowed for Day 1 in subsequent cycles post Cycle 1, Day 1):  
• Prior to each infusion of study drugs (within ≤72 hours unless otherwise stated):  
– Physical examination including weight 
– Vital signs (blood pressure, pulse, respiratory rate, pulse oximetry and temperature in 
resting position after 5 minutes rest) 
– ECOG performance status evaluation 
– Clinical safety labs (as described in Appendix B; results must be reviewed before 
dosing) 
– Collect sample if the patient is being followed for a tumor marker (e.g. CA-125, or 
others) on Cycle 3 Day 1, then every other cycle after, or as clinically indicated 
 
CA-125 is required for cohort 1b5 
– Radiological imaging: CT or MRI scan performed every 8 weeks (± 7 days) from the 
first dose for the first 12 months for patients who remain on treatment (and every 12 
weeks (± 7 days) thereafter) and 28 days (± 7 days) after the last dose of study 
treatment.  
‒ Serum pregnancy test (β-hCG) for women of childbearing potential on Cycle 5, Day 
1, then every 8 weeks (every 4 cycles) 
– Optional tumor biopsy collection (prior to Cycle 3 only; within 7 days prior to Cycle 
3 Day 1 and prior to 24 hours of dosing; analyses described in Appendix D) 
– Optional tumor biopsy for patients who responded to treatment (within 14 days post 
tumor assessment; for analyses described in Appendix D) 
– Blood collection for: 
 
Serum (analyses described in Appendix D) as listed below. 
– Cabiralizumab PK for Cycles 3, 4, 5, 8, 9, 13, and 21, then every 6 cycles 
while on treatment 
– Nivolumab PK for Cycles 3, 4, 5, 8, 9, 13, and 21  
– Cabiralizumab ADA for Cycles 3, 4, 5, 9, 13, and 21, then every 6 cycles 
while on treatment  
– Nivolumab ADA for Cycles 3, 4, 5, 8, 9, 13, and 21  

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– ANA for Cycles 3, 4, 5, 9, 13, 21, then every 6 cycles while on treatment 
– Selected serum markers for Cycles 3, 4, 5, 9, 13, and 21 
– Cytokine multiplex panel for Cycles 3, 4, 5, 8, 9, 13, and 21  
 
Whole blood (analyses described in Appendix D) as listed below. 
– CD14+/CD16+ monocytes for Cycles 3, 4, 5, 8, 9, 13, and 21, then every 6 
cycles while on treatment 
– Gene expression analysis for Cycles 3, 5, 9, 13, and 21, then every 6 cycles 
while on treatment 
– Frozen PBMC for Cycle 3 only (analyses described in Appendix D) 
– AE reporting, if applicable 
– Review of concomitant medications 
• Study drug administration: Nivolumab will be given first, with a 30- to 60-minute rest, 
followed by cabiralizumab. 
– Nivolumab administered by IV infusion over 30 minutes (± 5 minutes) (If any Grade 
3 or higher infusion reaction is observed during the proposed infusion rate of 
nivolumab 3 mg/kg over 30 minutes, the infusion rate will be extended to 60 minutes 
for all current and subsequent patients for the duration of this study) 
 Post-nivolumab administration during the 30- to 60-minute rest: 
– Post-dose vital signs (blood pressure, pulse, respiratory rate, and temperature 
in resting position after 5 minutes rest) at the following time point after 
completion of each IV infusion: 
 10 (±5) minutes 
– Blood collection for serum (for analyses described in Appendix D) as listed 
below. 
 15 minutes (±5 minutes) nivolumab PK for Cycle 8 only 
– Cabiralizumab administered by 30 minutes IV infusion (± 5 minutes) 
 Post cabiralizumab administration: 
– Post-dose vital signs (blood pressure, pulse, respiratory rate, and temperature 
in resting position after 5 minutes rest) at the following time points after 
completion of cabiralizumab IV infusion: 
 10 (±5) minutes, 30 (±10) minutes, and 60 (±15) minutes 
– Blood collection for serum (for analyses described in Appendix D) as listed 
below. 
 Cabiralizumab PK 15 minutes (±5 minutes) for Cycles 3 and 4 
 Cabiralizumab PK 15 minutes (±5 minutes), 4 hours (±60 minutes), 24 
hours (±6 hours), 72 hour (±12 hours) and 168 hours (±24 hours) Cycle 8 
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 Selected serum markers 72 hours (±12 hours) and 168 hours (± 24 hours) 
for Cycle 8 only 
 Cytokine multiplex panel 72 hours (±12 hours) and 168 hours (±24 hours) 
for Cycle 8 only  
 CD14+/CD16+ monocytes 72 hours (±12 hours) and 168 hours (±24 hours) 
for cycle 8 only 
5.2.3.8 
End-of-Treatment Follow-up Period 
Patients will return to the study center twice, approximately 28 (±7) days and 100 (±7) days after 
their last infusion of cabiralizumab and nivolumab to complete the End-of-Treatment Follow-up 
Period.  
The following assessments will be performed: 
• Physical examination including weight 
• Vital signs (blood pressure, pulse, respiratory rate, pulse oximetry and temperature in 
resting position after 5 minutes rest) 
• ECOG performance status evaluation 
• Clinical safety labs (as described in Appendix B) 
• 12-lead ECG (28 [±7] days post last infusion of cabiralizumab and nivolumab visit only) 
• Collect sample if the patient is being followed for a tumor marker (e.g. CA-125, or 
others) 
– CA-125 is require for cohort 1b5 
• Radiological imaging: CT or MRI scan does not need to be repeated if performed within 
8 weeks prior to the End-of-Treatment Visits or if tumor progression was previously 
determined. 
• Serum pregnancy test (β-hCG) for women of childbearing potential 
• Optional tumor biopsy for patients who progressed (28 [±7] days post last infusion of 
cabiralizumab and nivolumab visit only) (analyses described in Appendix D) 
• Blood collection 
– Serum (analyses described in Appendix D) 
– Whole blood (CD14+/CD16+ monocyte analysis and gene expression analysis) 
• AE reporting, until 100 (±7) days after the last dose of study drug or until initiation of 
subsequent anti-cancer therapy. Patients with ongoing SAEs will be followed until 
resolution or stabilization. 
• Review of concomitant medications 

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5.2.4 Long-Term Follow-up for All Patients 
Patients should continue onto Long-Term Follow-up after completing the End-of-Treatment 
Follow-up Period. 
Patients will be followed every 12 (±2) weeks for survival, or more frequently as needed. 
Patients who discontinue treatment while showing clinical benefit (complete response [CR], 
partial response [PR], or stable disease [SD]) should have tumor assessments during these visits 
for duration of response.  
Long-Term Follow-up for survival may be conducted by telephone, rather than by an in-person 
visit, once tumor progression is determined or use of subsequent anti-cancer therapy has been 
initiated. 
During the Long-Term Follow-up Period, if the patient undergoes local therapy (e.g., resection, 
radiation) or new systemic therapy is initiated, this should be documented. Patients should be 
followed until death, loss to follow-up, withdrawal of consent, or study termination by the 
Sponsor.  
5.3 
Study Assessments 
5.3.1 Safety Assessments 
At baseline, a medical history will be obtained to capture relevant underlying conditions. The 
baseline examinations should include weight, height, ECOG Performance Status (Appendix I), 
ECG, blood pressure, heart rate, temperature, and oxygen saturation by pulse oximetry at rest 
(also monitor amount of supplemental oxygen, if applicable) within 28 days prior to first dose.  
Safety assessments including serum hematology, chemistry, ECOG, weight and other 
assessments including ECG (if clinically indicated) will be done as part of standard care during 
each visit prior to dosing as noted in Appendix A, Appendix B, and Appendix C. Serum 
chemistry labs will be checked at screening and any abnormalities outside of the normal range 
will be followed closely with evaluation of symptoms and follow-up laboratory data. Patients 
will also be monitored for any infusion-related AEs during dosing and followed up accordingly 
based on protocol guidelines. Pre-medications including steroids, antihistamines or other 
treatments will be given prior to future dosing if a patient develops infusion reactions per 
protocol guidelines.  
Any patient who has received study drug will be evaluated for safety. Toxicity assessments will 
be continuous during the treatment phase and End-of-Treatment Follow-up Period clinic visits. 
Once patients reach the Long-Term Follow-up Period (and tumor progression has been 
determined or use of subsequent anti-cancer therapy has been initiated), documented telephone 
calls or email correspondence to assess the patient’s status are acceptable. 
AEs and laboratory values will be graded according to the NCI CTCAE v 4.03. 

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Oxygen saturation by pulse oximetry at rest (also the amount of supplemental oxygen, if 
applicable) should be assessed at each on-study visit prior to dosing. If a patient shows changes 
on pulse oximetry or other pulmonary-related signs (hypoxia, fever) or symptoms (e.g. dyspnea, 
cough, fever) consistent with possible pulmonary AEs, the patient should be immediately 
evaluated to rule out pulmonary toxicity, according to the suspected pulmonary toxicity 
management table in Appendix G. 
Physical examinations are to be performed as clinically indicated. If there are any new or 
worsening clinically significant changes since the last exam, report changes on the appropriate 
non-serious AE or SAE page. 
Additional measures, including non-study required laboratory tests, should be performed as 
clinically indicated or to comply with local regulations. Laboratory toxicities (e.g., suspected 
drug-induced liver enzyme evaluations) will be monitored during the follow-up phase via 
on-site/local labs until all study drug-related toxicities resolve, return to baseline, or are deemed 
stable. 
Additional testing or assessments may be performed as clinically necessary or as required by 
institutional or local regulations. 
5.3.2 Efficacy Assessments 
5.3.2.1 
Primary Efficacy Parameters 
The primary efficacy parameter is the objective response rate (ORR; number of patients with 
confirmed response of CR or PR, divided by the total number of patients who are evaluable for a 
response). Tumor response status will be assessed using RECIST v1.1 by investigator review.  
An Independent Radiology Facility will also be established to evaluate imaging data of trial 
subjects in a central and independent fashion. Board-certified radiologists will determine 
radiographic response and/or progression following enrollment in according to RECIST v1.1 
and/or RANO for Cohort 1b7. Response assesssments by independent review will be a secondary 
endpoint.  
5.3.2.1.1 Tumor Assessment 
Tumor assessments will be performed at Screening (within 28 days prior to first dose), then 
every 8 weeks (± 7 days) from the first dose, for the first 12 months, and then every 12 weeks 
(±7 days) thereafter. All patients should have tumor response parameters assessed at the End-of-
Treatment visit unless a tumor assessment has been performed within 8 weeks prior to an End-
of-Treatment Visit or if tumor progression was previously determined. Patients who enter Long-
Term Follow-up while showing clinical benefit should have tumor assessments every 12 weeks 
(±7 days) for duration of response. The same measuring modality should be preferably used by 
the site to maintain consistency across the study. 

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Response will be evaluated using RECIST v1.1 for measurable disease. Clinical lesions will only 
be considered measurable when they are superficial and ≥10 mm diameter as assessed using 
calipers. For the case of skin lesions, documentation by color photography including a ruler to 
estimate the size of the lesion is suggested. As previously noted, when lesions can be evaluated 
both by clinical exam and imaging, imaging evaluation should be undertaken since it is more 
objective and may also be reviewed at the end of the study. These assessments will follow the 
same schedule as the radiological assessments. 
5.3.2.2 
Additional Efficacy Parameters 
Additional efficacy parameters may include the following: Overall Survival (OS, 1-year OS, and 
median OS), progression-free survival (PFS), and duration of response (DOR) for those patients 
with confirmed responses, based on RECIST v 1.1.  
CT or MRI will be performed at screening, during treatment, and at the End-of-Treatment Visit 
per protocol. Measurements of change in tumor burden must be reviewed and documented after 
each measurement. 
5.3.2.3 
Tumor Biopsy or Fresh Tumor Tissue Collection 
Biopsy at the primary tumor site or metastatic site will be collected at screening (at least 24 
hours prior to dosing) and also on-treatment (prior to Cycle 3, Day 1, within 7 days prior to 
Cycle 3 Day 1 and at least 24 hours prior to dosing) for all Phase 1a patients and 10 patients per 
cohort in Phase 1b (optional for patients in the GBM cohort). Patients may also have on-
treatment biopsy upon documented tumor response and post-treatment biopsy upon documented 
tumor progression. The post-response and post-progression biopsies will be optional for patients 
in Phase 1a and Phase 1b (Appendix E). If available, tumor tissue obtained from post-treatment 
procedures such as surgery may also be collected. 
Biopsied lesions may become inflamed, bleed, or change dimensions, which could result in 
inaccurate tumor measurements. Therefore, it is recommended not to use the biopsied lesion as a 
target lesion when assessing the response by RECIST v 1.1 criteria. 
5.3.2.4 
Skin Biopsy Tissue Collection 
Skin Biopsy will be collected at screening (at least 24 hours prior to dosing) and on-treatment 
(prior to Cycle 3, Day 1, within 7 days prior to Cycle 3 Day 1 and at least 24 hours prior to 
dosing) for all Phase 1a patients. Patients may also have on-treatment skin biopsy upon 
documented tumor response and post-treatment skin biopsy upon documented tumor 
progression. The post-response and post-progression skin biopsies will be optional for patients in 
Phase 1a (Appendix E). It is recommended to biopsy in an area of skin that is devoid of disease 
(e.g. inflammation, rash, urticaria). 

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5.3.3 Pharmacokinetic Assessments 
Blood samples for the PK evaluation of both cabiralizumab and nivolumab will be collected 
from all patients. 
Patients enrolled in Phase 1a and Phase 1b will have blood drawn for measurement of serum 
cabiralizumab concentration. Blood samples will be collected during Cycle 1 and Cycle 8 on 
Days 1, 2, 4, and 8 as well as both before and after infusion for Cycle 2, 3 and 4. In addition, 
blood samples will be collected before the infusion on Cycles 5, 9, 13, and 21, then every 6 
cycles while on treatment. A blood sample will also be collected for PK analysis during the End-
of-Treatment Follow-up Period (28 [±7] days and 100 [±7] days post-last dose). 
Patients enrolled in the 3-week dosing regimen cohort (1aD) will have additional blood sample 
drawn on Day 15 of Cycles 1 and 8. See Appendix C for specific collection time points. 
Patients enrolled in Phase 1a and Phase 1b combination cohorts will have blood drawn for 
measurement of serum nivolumab concentration. Blood samples will be collected both before 
and at the end of infusion for Cycle 1 to Cycle 4. In addition, blood samples will be collected at 
the end of the infusion for Cycle 8 and before the infusion on Cycles 5, 9, 13, and 21. A blood 
sample will also be collected during the End-of-Treatment Follow-up Period. 
Standard PK parameters will be determined based on serum cabiralizumab concentration-time 
data, as appropriate. Nivolumab accumulation will be evaluated as appropriate. 
5.3.3.1 
Pharmacokinetic Collection and processing  
Blood samples will be collected and processed for serum according to the instructions provided 
in a Laboratory Manual. 
5.3.3.2 
Pharmacokinetic Sample Analysis 
Cabiralizumab concentration in serum will be determined in serum using a validated ELISA 
method. Nivolumab concentration in serum will be determined in serum using a validated ECLA 
method. 
5.3.4 Immunogenicity Assessments 
Blood samples will be collected before the infusion on Cycles 1, 2, 3, 4, 5, 9, 13, and 21, and at 
the 28 (±7) days and 100 (±7) days End-of-Treatment Visits to measure ADA for cabiralizumab 
and nivolumab. ADA for cabiralizumab in serum will be measured by a validated bridging 
ECLA that utilizes Meso Scale Discovery (MSD) technology. ADA for nivolumab in serum will 
be measured by a validated ECLA method. 
5.3.5 Biomarker Assessments 
A variety of factors that could potentially predict clinical response to the combination of 
cabiralizumab and nivolumab will be investigated in peripheral blood and in tumor specimens 

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5.3.5.4 
Flow Cytometry 
Pre-treatment and on-treatment whole blood and PBMC samples will be analyzed by flow 
cytometry to study the effects of cabiralizumab and nivolumab on various peripheral blood 
immune cell subsets. Whole blood samples will be assessed to confirm the predicted PD effect of 
cabiralizumab on the reduction of CD16+ monocytes. PBMC samples will be analyzed to 
determine whether blockade of PD-1 combined with CSF1R targeting will impact peripheral T-
cell levels and activation status. 
 Timing of sample collection is 
listed in Appendix C and analyses to be performed are described in Appendix D. 
 
 
 
 
 

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6. 
Adverse Events 
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a 
preexisting medical condition in a clinical investigation, patient-administered study drug and that 
does not necessarily have a causal relationship with this treatment. An AE can therefore be any 
unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of study drug, whether or not considered related to the study 
drug. 
The causal relationship to study drug is determined by an investigator and should be used to 
assess all AEs. The causal relationship can be one of the following: 
• Related: There is a reasonable causal relationship between study drug administration and 
the AE. 
• Not related: There is not a reasonable causal relationship between study drug 
administration and the AE.  
The term “reasonable causal relationship” means there is evidence to suggest a causal 
relationship.  
AEs can be spontaneously reported or elicited during open-ended questioning, examination, or 
evaluation of a patient. (In order to prevent reporting bias, patients should not be questioned 
regarding the specific occurrence of one or more AEs.) 
6.1 
Collection of Adverse Events 
Any new symptoms, injury or worsening of symptoms that occur following signing of the 
informed consent form (ICF) but prior to first infusion (Cycle 1 Day 1) will be considered 
pretreatment events and reported on the Medical History page of the electronic case report form 
(eCRF), unless they directly correlate to a study-related procedure. Adverse event reporting will 
continue until 100 (±7) days after the last dose of study drug or until initiation of subsequent 
anti-cancer therapy.  
6.2 
Serious Adverse Events 
A Serious Adverse Event (SAE) is 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 100 (±7) days after the last dose of cabiralizumab (or until 
initiation of subsequent anti-cancer therapy) must be treated as an SAE and reported as 
such. 
• Is life-threatening (defined as an event in which the patient was at risk of death at the 
time of the event) 
• Requires inpatient hospitalization or causes prolongation of existing hospitalization (see 
NOTE below) 

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• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly/birth defect  
• Is an important medical event (defined as a medical event that may not be immediately 
life-threatening or result in death or hospitalization but, based upon appropriate medical 
and scientific judgment, may jeopardize the patient or may require intervention [e.g., 
medical, surgical] to prevent one of the other serious outcomes listed in the definition 
above.) Examples of such events include, but are not limited to, intensive treatment in an 
emergency room or at home for allergic bronchospasm; blood dyscrasias or convulsions 
that do not result in hospitalization.) Potential drug-induced liver injury (DILI) is also 
considered an important medical event. (See Section 6.7 for the definition of potential 
DILIs.) 
Suspected transmission of an infectious agent (e.g., pathogenic or nonpathogenic) via the study 
drug is an SAE.  
Although pregnancy and potential DILI are not always serious by regulatory definition, these 
events must be handled as SAEs. (See Section 6.2.1 for reporting pregnancies). 
Note: The following hospitalizations are not considered SAEs in this clinical study:  
• Visit to the emergency room or other hospital department <24 hours, that does not result 
in admission (unless considered an important medical or life-threatening event) 
• Elective surgery, planned prior to signing consent 
• Admissions as per protocol for a planned medical/surgical procedure 
• Routine health assessment requiring admission for baseline/trending of health status 
(e.g., outine colonoscopy) 
• Medical/surgical admission other than to remedy ill health and planned prior to entry into 
the study. Appropriate documentation is required in these cases. 
• Admission encountered for another life circumstance that carries no bearing on health 
status and requires no medical/surgical intervention (e.g., lack of housing, economic 
inadequacy, caregiver respite, family circumstances, administrative reason). 
• Admission for administration of anti-cancer therapy in the absence of any other SAEs  
• Hospitalization for an event solely related to disease progression or for an elective or 
planned procedure to treat a pre-existing condition 
• Admission to hospice or care facility to support activities of daily living 

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6.2.1 Serious Adverse Event Reporting 
The Investigator should report any SAE that occurs after the first study drug dose and until 
100 (±7) days after the last dose of study drug or until initiation of subsequent anti-cancer 
therapy. Protocol-specified procedure related SAE will be collected following signing of ICF.  
An SAE report should be completed for any event where doubt exists regarding its seriousness.  
If the Investigator believes that an SAE is not related to study drug, but is potentially related to 
the conditions of the study (such as withdrawal of previous therapy or a complication of a study 
procedure), the relationship should be specified in the narrative section of the SAE Report Form. 
• SAEs, related or unrelated to study drug, and pregnancies must be reported to the 
Sponsor (or designee) within 24 hours of becoming aware of the event. SAEs must be 
recorded on the SAE Report Form, and pregnancies must be recorded on a Pregnancy 
Surveillance Form (paper forms). SAE and pregnancy data reporting must be done on the 
paper SAE/Pregnancy Surveillance Forms provided by the Sponsor (or designee). They 
are to be transmitted via email or fax 
  
 
 
 
 
 
 
If only limited information is initially available, follow-up reports are required. 
Note: Follow-up SAE reports should include the same Investigator term(s) initially reported.  
If an ongoing SAE changes in intensity or relationship to study drug or if new information 
becomes available, a follow-up SAE report should be sent within 24 hours to the Sponsor (or 
designee) using the same procedure used for transmitting the initial SAE report.  
All SAEs should be followed to resolution or stabilization. 
6.3 
Non-Serious Adverse Events 
A non-serious adverse event is any AE not classified as serious. 
6.3.1 Non-serious Adverse Event Reporting 
Non-serious AEs should also be followed to resolution or stabilization, or reported as SAEs if 
they become serious (see Section 6.2.1). Follow-up is also required for non-serious AEs that 
cause interruption or discontinuation of study drug and for those present at the end-of-study 
treatment, as appropriate. All identified non-serious AEs must be recorded and described on the 
appropriate AE page of the CRF.  

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Completion of supplemental CRFs may be requested for AEs and/or laboratory abnormalities 
that are reported during the course of the study. 
6.4 
Laboratory Test Result Abnormalities 
The following laboratory test result abnormalities should be captured on the appropriate CRF 
page or SAE Report Form as appropriate: 
• Any laboratory test result that is clinically significant or meets the definition of an SAE 
• Any laboratory test result abnormality that required the patient to have study drug 
discontinued or interrupted 
• Any laboratory test result abnormality that required the patient to receive specific 
corrective therapy. 
It is expected that wherever possible, the clinical rather than laboratory term would be used by 
the reporting Investigator (e.g., anemia versus low hemoglobin value). 
6.5 
Pregnancy 
If, following initiation of the investigational product, it is discovered that a study patient is 
pregnant or may have been pregnant at the time of investigational product exposure, including 
during at least 5 half-lives (90 days) after product administration, the investigational product will 
be permanently discontinued in an appropriate manner. 
The Investigator must immediately notify the Sponsor’s (or designee’s) Medical Monitor of this 
event and complete and forward a Pregnancy Form to the Sponsor (or designee) within 24 hours 
and in accordance with SAE reporting procedures described in Section 6.2.1. 
Follow-up information regarding the course of the pregnancy, including perinatal and neonatal 
outcome and, where applicable, offspring information, must be reported on the Pregnancy 
Surveillance Form. 
Any pregnancy that occurs in a female partner of a male study participant should be reported to 
the Sponsor. Information on this pregnancy will be collected on the Pregnancy Surveillance 
Form. 
6.6 
Overdose 
Any dose of study drug in excess of 50% of the dose level specified in the protocol is considered 
to be an overdose. Signs and symptoms of an overdose that meet any SAE criterion must be 
reported as an SAE in the appropriate time frame and documented as clinical sequelae to an 
overdose. There is no known antidote for a drug overdose to either cabiralizumab or nivolumab. 
In the event of an overdose, patients should be closely monitored and given appropriate 
supportive treatment. 

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6.7 
Potential Drug Induced Liver Injury 
Wherever possible, timely confirmation of initial liver-related laboratory abnormalities should 
occur prior to the reporting of a potential drug-induced liver injury (DILI) event. All occurrences 
of potential DILIs, meeting the defined criteria, must be reported as SAEs. 
Potential drug induced liver injury is defined as:  
1. 
ALT or AST elevation >3x ULN 
 
and  
2. 
Total bilirubin >2x ULN without initial findings of cholestasis (elevated serum alkaline 
phosphatase) or INR > 1.5 xULN (in the absence of anticoagulation) 
 
and  
3. 
No other immediately apparent possible causes of aminotransferase elevation and 
hyperbilirubinemia including but not limited to viral hepatitis, pre-existing chronic or acute 
liver disease, or the administration of other drugs known to be hepatotoxic.  

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7. 
Statistical Considerations 
All analyses will be descriptive and will be presented by dose group and overall 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 mean, 
median, standard deviation, minimum, and maximum. Categorical variables will be summarized 
by frequencies and percentages. 
7.1 
Sample Size Determination 
Approximately 85 patients will be enrolled in Phase 1a. In dose escalation, between 3 and 9 
patients are expected to be treated at each dose escalation cohort according to the algorithm 
outlined in Table 2 . There will also be up to 40 patients enrolled into the exploratory dose 
cohorts to further explore safety, PK, and PD, and approximately 10 patients enolled into the 3-
week dosing regimen cohort to characterize the PK and safety profile at a 3-week dosing 
schedule. In Phase 1b, approximately 210 patients will be enrolled. 
7.2 
Populations for Analyses 
• Enrolled Population: All patients who sign the ICF and are approved for enrollment by 
sponsor or designee, and for Phase 1b patients only, are registered in IXRS. 
• Evaluable Population: Patients who have a measureable lesion at baseline and have at 
least 1 post-baseline tumor assessment or patients with the clinical progression or 
experiencing death event without any post baseline tumor assessment.  
• Safety Population: All patients who receive at least one dose of cabiralizumab and/or 
nivolumab. 
• PK Population: All patients who receive at least one dose of cabiralizumab and/or 
nivolumab and have available serum concentration data. 
• Biomarker Patients: All patients who receive at least one dose of cabiralizumab and/or 
nivolumab and have available biomarker data. 
• Immunogenicity Patients: All patients who receive at least one dose of cabiralizumab 
and/or nivolumab and have available ADA data. 
7.3 
Endpoints 
7.3.1 Phase 1a Endpoints 
7.3.1.1 
Primary  
• Safety  
– 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 

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7.3.1.2 
Secondary  
• Pharmacokinetic: The following PK parameters will be derived from concentration-time 
data for cabiralizumab when appropriate and applicable. Other parameters, such as dose 
dependency and accumulation ratio, may also be calculated. Accumulation ratio of Cmax 
and Cmin for nivolumab may be caculated if the data are available.  
– Area under serum concentration-time curve (AUC) 
– Maximum serum concentration (Cmax) 
– Minimum serum concentration (Cmin) 
– Clearance (CL) 
– Volume of distribution at steady state (Vss) 
• Immunogenicity: Defined as an immune response to either cabiralizumab or nivolumab, 
will be assessed by measurement of total anti-FPA008 antibodies and total anti-
nivolumab antibodies from all patients. Immunogenicity testing will consist of screening, 
confirmation, and titration for both cabiralizumab and nivolumab. 
• Pharmacodynamic Biomarkers  
– Changes in whole blood monocyte subsets by flow cytometry 
– Changes in cytokine levels by multiplex analysis 
– Change in macrophage and T-cell levels in tumor biopsy samples 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
7.3.2 Phase 1b Endpoints 
7.3.2.1 
Primary  
• Efficacy  
– ORR will be defined as the total number of patients with confirmed responses of 
either CR or PR divided by the total number of patients who are evaluable for a 
response per RECIST v1.1 by investigator assessment 

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• Safety 
– The incidence of AEs, SAEs, clinical laboratory abnormalities, and ECG 
abnormalities 
– The incidence of treatment discontinuations, modifications, and interruptions due to 
adverse events  
– Grade 3 and Grade 4 AEs and clinical laboratory abnormalities  
 
7.3.2.2 
Secondary  
• Pharmacokinetic: The following PK parameters will be derived from concentration-time 
data for cabiralizumab when appropriate and applicable. Other parameters, such as dose 
dependency and accumulation ratio, may also be calculated. Accumulation ratio of Cmax 
and Cmin for nivolumab may be caculated if the data are available.  
– Area under serum concentration-time curve (AUC) 
– Maximum serum concentration (Cmax) 
– Minimum serum concentration (Cmin)  
– Clearance (CL)  
– Volume of distribution at steady state (Vss) 
• Immunogenicity: Defined as an immune response to either cabiralizumab or nivolumab, 
will be assessed by measurement of total anti-FPA008 antibodies and total anti-
nivolumab antibodies from all patients. Immunogenicity testing will consist of screening, 
confirmation, and titration for both cabiralizumab and nivolumab. The results will be 
classified into incidence of ADA at baseline and after initiation of treatment. 
• Pharmacodynamic Biomarkers  
– Changes in whole blood monocyte subsets by flow cytometry 
– Changes in cytokine levels by multiplex analysis 
– Change in macrophage and T-cell levels in tumor biopsy samples 
• Efficacy  
– OS will be defined as the time between the first dose of study drug and death. 
 
One-year OS rate 
 
Median OS 
– DOR will be defined as the time from response (CR or PR) until the first objectively 
documented PD per RECIST v1.1 
– PFS will be defined for each patient as the time from the first dose to the first 
objectively documented of disease progression per RECIST v1.1 or death due to any 
cause.  

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– ORR by Central Imaging Review 
 
  
 
  
 
 
 
 
 
 
 
 
7.4 
Analyses 
7.4.1 Demographics and Baseline Characteristics 
Demographic data, medical history, other baseline characteristics, concomitant disease, and 
concomitant medication will be summarized by cohort and overall. To determine whether the 
criteria for study conduct are met, corresponding tables and listings will be provided. These will 
include an assessment of protocol deviations, study drug accountability, and other data that may 
impact the general conduct of the study. 
7.4.2 Efficacy Analyses 
For each disease type, response to treatment will be summarized for ORR, defined as the ratio of 
the number of patients that achieve an objective response (a BOR of CR or PR) to total number 
of patients who are evaluable for a response. Exact confidence interval will be constructed for 
the response rate. Overall Survival, survival at 1 year, and median survival will be estimated by 
the Kaplan-Meier method. The corresponding confidence interval will also be presented. 
7.4.3 Safety Analyses 
Safety analyses will be performed for patients included in the safety population. Incidence of 
AEs, clinical laboratory information, vital signs, ECOG performance status, weight, and ECGs 
will be tabulated and summarized.  
Incidence of AEs will be summarized overall and with separate summaries for SAEs, AEs 
leading to discontinuation, AEs leading to death, and NCI-CTCAE v 4.03 Grade 3 or higher 
AEs.  
Weight and vital signs will be summarized descriptively (n, mean, standard deviation, 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. A marked 
laboratory change is defined as a shift from a baseline Grade 0 to Grade 3 (non-hematologic) or 

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Grade 4 (hematologic) on treatment, or a shift from a baseline Grade 1 to Grade 4 on treatment. 
The number and percentage of patients with marked laboratory changes will be tabulated by 
cohort and overall. 
7.4.4 Pharmacokinetic Analyses 
Individual and mean serum concentration of cabiralizumab and nivolumab versus time data will 
be plotted by dose level. Summary statistics will be tabulated for the serum concentration-time 
data and estimated PK parameters of cabiralizumab, as appropriate.  
For cabiralizumab, PK parameters including Cmax, AUC, Cmin, CL, and Vss will be estimated. 
Other PK parameters as well as inter-patient variability, cabiralizumab accumulation, and dose 
proportionality will be evaluated when data are available. Nivolumab accumulation will be 
evaluated as appropriate. PK data (cabiralizumab and/or nivolumab) collected from this study 
may be used in combination with other studies for exposure-response or population PK 
modeling, which will be part of a separate report. 
7.4.5 Immunogenicity 
A listing will be provided of all available immunogenicity data for both cabiralizumab and 
nivolumab. Additionally, a listing of immunogenicity data from those patients with at least one 
positive ADA at any time point will be provided by dose level. The frequency of patients with at 
least one positive ADA assessment, and frequency of patients who develop ADA after a negative 
baseline assessment will be provided by dose. To examine the potential relationship between 
immunogenicity and safety, the frequency and type of AEs of special interest may be examined 
by overall immunogenicity status. Associations between pre-dose concentrations of 
cabiralizumab or nivolumab and corresponding ADA assessments may be explored. 
 
 
 
 
 
 
 
 
 
 
 

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7.5 
Interim Analysis 
No formal interim analysis is planned. 
The Sponsor (and/or designee) and Investigators will review safety data from each dose cohort 
prior to dose escalation or de-escalation. In addition, an interim data summary may be performed 
at several times prior to completion of the study in order to facilitate program decisions and to 
support presentations or publications. 

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8. 
Cohort Review Committee  
The Cohort Review Committee will consist of representatives from the Sponsor, contract 
research organization (CRO), as well as one or more designated Investigators from actively 
participating sites in which cabiralizumab and nivolumab are being evaluated. During Phase 1a, 
the Cohort Review Committee will assess safety of the study prior to making dose escalation 
decisions. The Cohort Review Committee will provide guidance on the continuation of the study 
including the escalation or de-escalation of dose levels. The committee members will review 
relevant data including AEs, SAEs, laboratory values, and other information. All correspondence 
during the cohort review meeting will be documented along with any decisions for further 
expansion, escalation, or discontinuation at the current dose level. 

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9. 
Ethical Considerations 
9.1 
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 
 The 
study also will be carried out in compliance with local legal requirements. 
The study will be conducted in compliance with the protocol. The protocol and any amendments 
and the Informed Consent Form (ICF) will receive Institutional Review Board/Independent 
Ethics Committee (IRB/IEC) approval/favorable opinion prior to initiation of the study.  
All potential serious breaches must be reported to the Sponsor immediately. A serious breach is a 
breach of the conditions and principles of GCP in connection with the study or the protocol, 
which is likely to affect, to a significant degree, the safety or physical or mental integrity of the 
patients of the study or the scientific value of the study. 
Personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective tasks. 
This study will not use the services of study personnel where sanctions have been invoked or 
where there has been scientific misconduct or fraud (e.g., loss of medical licensure, debarment). 
9.2 
Institutional Review Board/Independent Ethics Committee  
Before study initiation, the Investigator must have written and dated approval/favorable opinion 
from the IRB/IEC for the protocol, ICF, patient recruitment materials (e.g., advertisements), and 
any other written information to be provided to patients. The Investigator or Sponsor should also 
provide the IRB/IEC with a copy of the IB or product labeling information to be provided to 
patients and any updates.  
The Investigator should provide the IRB/IEC with reports, updates and other information (e.g., 
expedited safety reports, amendments, and administrative letters) according to regulatory 
requirements or institution procedures. 
9.3 
Informed Consent 
All information about the clinical study, including patient information and the ICF, is prepared 
and used for the protection of the human rights of the patient according to ICH GCP guidelines 
and the 
 
The ICF, 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. A copy of the signed ICF will be retained by the patient and 
the original will be filed in the Investigator’s site file, unless otherwise agreed. The Investigator 

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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 CRF.  
If a protocol amendment is required, the ICF may need to be revised to reflect the changes to the 
protocol. If the ICF 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. 
All signed and dated ICFs must remain in each patient’s study file and must be available for 
verification by study monitors at any time.  
The rights, safety, and well-being of the patients are the most important considerations and 
should prevail over interests of science and society. 

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10. 
Study Management 
10.1 
Compliance 
10.1.1 Compliance with the Protocol and Protocol Revisions 
The study shall be conducted as described in this approved protocol. All revisions to the protocol 
must be discussed with, and be prepared by, the Sponsor. The Investigator should not implement 
any deviation or change to the protocol without prior review and documented approval/favorable 
opinion from the IRB/IEC of an amendment, except where necessary to eliminate an immediate 
hazard(s) to Patients. 
If a deviation or change to a protocol is implemented to eliminate an immediate hazard prior to 
obtaining IRB/IEC approval/favorable opinion, as soon as possible the deviation or change will 
be submitted to: 
• IRB/IEC for review and approval/favorable opinion 
• Sponsor 
• Regulatory Authorities, if required by local regulations 
Documentation of approval signed by the chairperson or designee of the IRB(s)/IEC(s) must be 
sent to the Sponsor. 
If an amendment substantially alters the study design or increases the potential risk to the patient: 
(1) the consent form must be revised and submitted to the IRB(s)/IEC(s) for review and 
approval/favorable opinion; (2) the revised form must be used to obtain consent from patients 
currently enrolled in the study if they are affected by the amendment; and (3) the new form must 
be used to obtain consent from new patients prior to enrollment. 
If the revision is an administrative letter, investigators must inform their IRB(s)/IEC(s). 
10.1.2 Monitoring 
During the study, a monitor will perform routine site visits to review protocol compliance, 
compare CRFs and individual patients’ medical records, assess drug accountability, and ensure 
that the study is being conducted according to pertinent regulatory requirements. CRF 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.  
Representatives of the Sponsor will review data centrally to identify potential issues to determine 
a schedule of on-site visits for targeted review of study records.  
All participating centers should take particular care in ensuring that original imaging source data 
(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 

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(Section 10.2.1). These images must be stored in a secure location until the Sponsor (or 
designee) authorizes their destruction, and must be retrievable by study patient number in the 
event of an audit. 
10.1.2.1 
Source Documentation 
All data obtained during this study should be entered into the CRFs promptly. All source 
documents from which CRF entries are derived should be placed in the patient’s medical 
records. CRF fields for which source documents will typically be needed include laboratory 
assessments, physical exam reports, nursing notes, ECG recordings, hospital records, and CT or 
MRI reports.  
The CRFs 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. 
10.1.3 Investigational Site Training 
The Sponsor or designee will provide quality investigational staff training prior to study 
initiation. Training topics will include but are not limited to: GCP, AE reporting, study details 
and procedure, CRFs, study documentation, informed consent, and enrollment of WOCBP. 
10.2 
Records 
10.2.1 Records Retention 
The study site will maintain a study file, which should contain, at minimum, the Investigator’s 
Brochure, 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 FivePrime 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 
regulations 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. 

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No data should be destroyed without the agreement of FivePrime. Should the Investigator wish 
to assign the study records to another party or move them to another location, FivePrime 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.  
10.2.2 Study Drug Records  
It is the responsibility of the Investigator to ensure that a current disposition record of each study 
drug (supplied by FivePrime) is maintained at each study site where study drugs are inventoried 
and dispensed. Records or logs must comply with applicable regulations and guidelines and 
should include: 
• Amount received and placed in storage area 
• Amount currently in storage area 
• Label identification number or batch number 
• Amount dispensed to and returned by each patient, including unique patient identifiers 
• Non-study disposition (e.g., lost, wasted) 
• Amount destroyed at study site, if applicable 
• Amount returned to designated parties 
• Dates and initials of person responsible for Investigational Product 
dispensing/accountability as per the Delegation of Authority Form. 
The Sponsor will provide forms to facilitate inventory control if the investigational site does not 
have an established system that meets these requirements. 
10.2.2.1 
Case Report Forms 
An Investigator is required to prepare and maintain adequate and accurate case histories designed 
to record all observations and other data pertinent to the investigation on each individual treated 
or entered as a control in the investigation. Data that are derived from source documents and 
reported on the CRF must be consistent with the source documents or the discrepancies must be 
explained. 
For sites using the electronic data capture tool, eCRFs will be prepared for all data collection 
fields except for fields specific to SAEs and pregnancy, which will be reported on the paperSAE 
form and Pregnancy Surveillance form, respectively. Spaces may be left blank only in those 
circumstances permitted by study-specific CRF completion guidelines provided by the Sponsor. 
The confidentiality of records that could identify patients must be protected, respecting the 
privacy and confidentiality rules in accordance with the applicable regulatory requirement(s). 

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The Investigator will maintain a signature sheet to document signatures and initials of all persons 
authorized to make entries and/or corrections on CRFs. 
The completed CRF, including any paper SAE/pregnancy report forms, must be promptly 
reviewed, signed, and dated by the Investigator or qualified physician who is a subinvestigator 
and who is delegated this task on the Delegation of Authority Form. For eCRFs, review and 
approval/signature is completed electronically using the Sponsor’s electronic data capture tool.  
The Investigator must retain a copy of the CRFs including records of the changes and 
corrections. Each individual electronically signing eCRFs must meet the Sponsor’s training 
requirements and must only access the Sponsor’s electronic data capture tool using the unique 
user account provided by the Sponsor. User accounts are not to be shared or reassigned to other 
individuals. 

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Notes for Phase 1a Schedule of Assessments 
a. 
Unless specified, prior to infusion procedures are to be completed within 72 hours of scheduled time point and to be synchronized with administration of assigned study drug. Any clinical 
assessment, laboratory study, or additional non-specified tests may be obtained at any time, if clinically indicated. 
b. Each cycle will be 14 days long, with administration of cabiralizumab ± nivolumab on Day 1. In Cohort 1aD, each cycle will be 3 weeks long, with administration of cabiralizumab and nivolumab 
on Day 1. The first day of treatment in Cycle 1 is defined as Day 1; a ± 2 day window is allowed for Day 1 in subsequent cycles.  
c. 
Day 15 Assessments (Physical Examination, Vital Signs and Clinical Safety Lab) will apply to patients in Cohort 1aD only 
d. Standard physical examination will be performed as determined by the Investigator, particularly to follow physical findings to resolution. Targeted physical exams should be conducted at any time 
to follow up on AE reports.  
e. 
Height is only required to be recorded at screening. Weight is required to be recorded at Day 1 of each cycle. Dose will be adjusted only if weight change is >10% from first dose on Cycle 1 Day 1. 
f. 
Vital signs include pulse, respiratory rate, blood pressure, and temperature in the resting position (sitting or supine). Measure prior to dose and after completion of each IV infusion at the following 
time points: 10 (±5) minutes, 30 (±10) minutes, and 60 (±15) minutes, 168 hours (±24 hours) [Cycle 1 only] post cabiralizumab administration; 10 (±5) minutes post nivolumab administration. 
Pulse oximetry is performed at rest prior to dosing for the combination cohorts only. 
g. Patient ECOG Status assessments are to be performed within 72 hours prior to dosing (Day 1 of each cycle). 
h. Screening labs include serology for Hepatitis B (HBsAg), Hepatitis C (HCV antibody), and test for latent TB (e.g. T-SPOT, Quantiferon).  
i. 
Clinical Safety Labs: 
Hematology including CBC with differential, platelets, hemoglobin, hematocrit, RBC, and RBC indices 
Chemistry includes CK (creatine kinase), AST (aspartate transaminase), ALT (alanine transaminase), alkaline phosphatase, bicarbonate, bilirubin, (direct and total), BUN (blood urea nitrogen), 
calcium, chloride, creatinine, glucose, LDH (lactate dehydrogenase), phosphorus, potassium, sodium, and, if applicable, serum pregnancy. Albumin, amylase, lipase, thyroid panel includes TSH, 
Free T3 and Free T4, PT/INR, and PTT (aPTT) perform at Screening and as indicated. If CK elevation is clinically significant, obtain troponins (cardiac and skeletal), CK isoenzymes, aldolase, 
and ECG; repeat CK and these additional tests within 48 hours or other interval as clinically indicated, until resolved or stable. If either AST or ALT is elevated, obtain total serum bilirubin, 
alkaline phosphatase; repeat within 48 hours or other interval, as clinically indicated, until resolved or stable. Additional tests may be obtained at any time, if clinically indicated. If a patient is 
being followed for a tumor marker (e.g. CA-125, or others), a sample for the tumor marker should be obtained at screening and every other cycle, or if clinically indicated during the study 
Urinalysis: Urine dipstick will only be done at screening, and when clinically indicated. 
j. 
Obtain ECG records at Screening and the Day 28 post last infusion End-of-Treatment Visit (after PK blood draw, record exact time). 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. 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 (e.g., television, radio, conversation) should be avoided during the pre-ECG resting period and during ECG recording.  
k. CT or MRI of the Tumor sites measured as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1). If patient terminates prior to scheduled CT or MRI scans, patient should have scans 
done at End-of-Treatment Visits (does not need to be repeated if performed within 8 weeks prior to End-of-Treatment Visits or if tumor progression was previously determined). Patients who enter 
Long-Term Follow-up while showing clinical benefit should have tumor assessments q12w for duration of response. The same measuring modality should be used by the site to maintain 
consistency across the various time points. (Documentation of skin lesions by color photography, including a ruler to measure the size of the lesion, is suggested and should follow the CT or MRI 
schedule.) Brain scans will be required only if CNS metastasis is suspected, based on Investigator clinical judgment (except for patients in cohort 1b7). 
l. 
Performed every 8 weeks (±7 days) from the first dose for the first 12 months for patients who remain on treatment (and every 12 weeks (±7 days) thereafter) and 28 days (± 7 days) after the last 
dose of study treatment. CT or MRI scans do not need to be repeated if performed within 8 weeks prior to the End-of-Treatment Visits or if tumor progression was previously determined. 
m. All women of childbearing potential will have a serum pregnancy test at screening, Cycle 1 Day 1 and every 8 weeks during treatment, and at the End-of-Treatment Visits. 
n. Biopsy at primary tumor or metastatic tumor site and skin biopsy from a site devoid of disease (e.g. rash or urticaira) will be collected at screening [at least 24 hours prior to dosing] and prior to 
Cycle 3 Day 1 [within 7 days prior to Cycle 3 Day 1 and at least 24 hours prior to dosing]. It is recommended that patients who have documented response receive another biopsy within 28 (±14) 
days post tumor assessment and/or patient who have progression receive another biopsy at the final End-of–Treatment visit. The post-response and post-progression biopsies are optional. If 
available, collect an FFPE tissue block or 10 slides of archival tumor sample at Screening.  
o. 
Samples will be collected for PK, PD, and ADA analyses. Not all visits will require collection of all three – see Appendix C for collection schedule. 
p. 
Blood will be collected to evaluate Cmax and/or Cmin on Day 1 of study drugs on Cycles 1, 2, 3, 4, 5, 8, 9, 13, 21, then every 6 cycles while on treatment and End-of-Treatment Follow up Period. 
Cycles 1 and 8 will have additional samples on days 2, 4, and 8 (and day 15 for patients in Cohort 1aD). 
q. 
Antinuclear antibody (ANA) samples will be collected prior to dose at Cycles 1, 2, 3, 4, 5, 9, 13, 21, then every 6 cycles while on treatment and at End-of-Treatment Visits. Additional ANA reflex 
samples may be collected upon requested or as clinically indicated. Testing by indirect fluorescent antibody (IFA) will be performed as clinically indicated. If the titer is positive, erythrocyte 

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sedimentation rate (ESR) and C-reactive protein (CRP) will be tested to confirm the result.  
r. 
Cabiralizumab and nivolumab will both be administered by IV infusion over 30 minutes (± 5 minutes). If any Grade 3 or higher infusion reaction is observed during the proposed infusion rate of 
nivolumab 3 mg/kg over 30 minutes, the infusion rate will be extended to 60 minutes for all current and subsequent patients for the duration of this study. Nivolumab will be given first, with a 30- 
to 60-minute rest, followed by cabiralizumab as a 30-minute infusion. 
s. 
Cabiralizumab ± nivolumab will be administered every 2 weeks in 14-day cycles. Patients in Cohort 1aD, cabiralizumab and nivolumab will be administered every 3 weeks. The dosing may 
continue until PD or unacceptable toxicity. 
t. 
These assessments are to be performed prior to each dose (with the exceptions noted in Appendix C) for those patients who continue treatment without signs of progressive disease or toxicity. 
u. 
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 
subsequent anti-cancer therapy has not been initiated. Any new anti-cancer therapy should be documented. 
 
 

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Appendix B: Schedule of Assessments – Phase 1b Cabiralizumab + Nivolumab  
Procedurea 
Screening 
Cycle 1 
Cycle 2 
Cycle xs 
Cycle 8 
End-of-Treatment 
Follow-up Period 
Long-
Term 
Follow-up 
Periodt 
Day –28 to 
Day 0 
Day 1b 
Day 2 
Day 4 
Day 8 
Day 1b 
Day 1b 
Days 2, 4, 8 
28 (±7) days and 
100 (±7) days post-
last dose 
Week 0 
Week 1 
Week 2 
Week 3 
Week ≥5 
 
Informed Consent 
x 
 
 
Review/Confirm Eligibility 
Criteria 
x 
x 
 
 
Medical History / 
Demographics 
x 
x 
 
 
Physical Examinationc 
x 
x 
x 
x 
x 
 
x 
 
Height and Weightd 
x 
x 
x 
x 
 
x 
 
Vital Signse 
x 
x 
x 
x 
x 
 
x 
 
ECOG Performance Statusf 
x 
x 
x 
x 
 
x 
 
Screening Labsg 
x 
 
 
Clinical Safety Labsh 
x 
x 
x 
x 
x 
 
x 
 
12-Lead ECGi 
x 
 
x 
 
CT or MRI Tumor 
Assessmentj,k 
x 
 
 
 
 
 
x 
 
x 
x 
Serum Pregnancy Testl 
x 
x 
 
 
 
 
x 
 
x 
 
Tumor Biopsym 
x 
 
 
 
 
 
x 
 
x 
 
PK Samplingn,o 
 
x 
x 
x 
x 
x 
x 
x 
x 
 
PD Samplingn 
 
x 
 
x 
x 
x 
x 
x 
x 
 
ADA Samplingn 
x 
x 
x 
 
x 
 
ANA Samplingp 
 
x 
 
 
 
x 
x 
 
x 
 
Study Drugsq,r  
x 
x 
x 
 
 
Adverse Events 
 
x–––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––––x 
 
 
 
 
 
Long-Term Follow-up 
Contactst 
 
x 

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Notes for Phase 1b Schedule of Assessments 
a. 
Unless specified, prior to infusion procedure are to be completed within 72 hours of scheduled time point and to be synchronized with administration day of cabiralizumab infusion. Any clinical 
assessment, laboratory study, or additional non-specified tests may be obtained at any time, if clinically indicated. 
b. 
Each cycle will be 14 days long, with administration of cabiralizumab + nivolumab on Day 1. The first day of treatment in Cycle 1 is defined as Day 1; a ± 2 day window is allowed for Day 1 in 
subsequent cycles.  
c. 
Standard physical examination will be performed, particularly to follow physical findings to resolution. Targeted physical exams should be conducted at any time to follow up on AE reports.  
d. 
Height is only required to be recorded at screening. Weight is required to be recorded at Day 1 of each cycle. Dose will be adjusted only if weight change is >10% from first dose. 
e. 
Vital signs include pulse, respiratory rate, blood pressure, and temperature in the resting position (sitting or supine). Measure prior to dose and after completion of the IV infusion at the following 
time points: 10 (±5) minutes, 30 (±10) minutes, and 60 (±15) minutes, 168 hours (±24 hours) [Cycle 1 only] post cabiralizumab administration; 10 (±5) minutes post nivolumab administration. 
Pulse oximetry is performed at rest prior to dosing only. 
f. 
Patient ECOG Status assessments are to be performed within 96 hours prior to dosing (Day 1 of each cycle). 
g. 
Screening labs include serology for Hepatitis B (HBsAg), Hepatitis C (HCV antibody), and test for latent TB (e.g. T-SPOT, Quantiferon) 
h. 
Clinical Safety Labs: 
Hematology including CBC with differential, platelets, hemoglobin, hematocrit, RBC, and RBC indices. 
Chemistry includes CK (creatine kinase), AST (aspartate transaminase), ALT (alanine transaminase), alkaline phosphatase bicarbonate, bilirubin, (direct and total), BUN (blood urea nitrogen), 
calcium, chloride, creatinine, glucose, LDH (lactate dehydrogenase), phosphorus, potassium, sodium, and, if applicable, serum pregnancy. Albumin, amylase, lipase, thyroid panel includes TSH, 
Free T3 and Free T4, PT/INR, and PTT (aPTT) perform at Screening and as indicated, If CK elevation is clinically significant, obtain troponins (cardiac and skeletal), CK isoenzymes, aldolase, 
and ECG; repeat CK and these additional tests within 48 hours or other interval as clinically indicated, until resolved or stable. If either AST or ALT is elevated, obtain total serum bilirubin, 
alkaline phosphatase; repeat within 48 hours or other interval, as clinically indicated, until resolved or stable. Additional tests may be obtained at any time, if clinically indicated. If a patient is 
being followed for a tumor marker (e.g. CA-125, or others), a sample for the tumor marker should be obtained at screening and every other cycle, or if clinically indicated during the study. 
Urinalysis: Urine dipstick will only be done at screening, and when clinically indicated. 
i. 
Obtain ECG records at screening and the Day 28 post last infusion End-of-Treatment Visit (after PK/PD blood draw, record exact time). 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. ECGs for each 
patient should be obtained from the same machine whenever possible. 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 (e.g., television, radio, conversation) should be 
avoided during the pre-ECG resting period and during ECG recording. Additional tests may be obtained at any time, if clinically indicated. 
j. 
CT or MRI of the Tumor sites measured as per Response Evaluation Criteria in Solid Tumors (RECIST v1.1). If patient terminates prior to scheduled CT or MRI scan, patient should have scans 
done at End-of-Treatment Visits (does not need to be repeated if performed within 8 weeks prior to End-of-Treatment Visits or if tumor progression was previously determined). Patients who enter 
Long-Term Follow-up while showing clinical benefit should have tumor assessments q12w for duration of response. Response per CT or MRI will be assessed using RECIST v1.1. The same 
measuring modality should be preferably used by the site to maintain consistency across the various time points. (Documentation of skin lesions by color photography, including a ruler to measure 
the size of the lesion, is suggested and should follow the CT or MRI schedule.) Brain scans will be required only if CNS metastasis is suspected, based on Investigator clinical judgment (except for 
patients in cohort 1b7). 
k. 
Performed every 8 weeks (±7 days) from the first dose for the first 12 months for patients who remain on treatment, and every 12 weeks (±7 days) thereafter. CT or MRI scans do not need to be 
repeated if performed within 8 weeks prior to an End-of-Treatment Visit or if tumor progression was previously determined. 
l. 
All women of childbearing potential will have a serum pregnancy test at screening, Cycle 1 Day 1 and every 8 weeks while on treatment, and at End-of-Treatment Visits. 
m. Biopsy at primary tumor or metastatic tumor site will be collected at screening [at least 24 hours prior to dosing] and prior to Cycle 3, Day 1 [within 7 days prior to Cycle 3 Day 1 and at least 24 
hours prior to dosing]. It is recommended that patients who have documented response receive another biopsy within 28 (±14) days post tumor assessment and/or patient who have progression 
receive another biopsy at the 28-days End-of–Treatment visit. The post-response and post-progression biopsies are optional. If available, collect an FFPE tissue block or 10 slides of archival tumor 
sample at Screening. 
n. 
Samples will be collected for PK, PD, and ADA analyses. Not all visits will require collection of all three – see Appendix C for collection schedule. 
o. 
Blood will be collected to evaluate Cmax and/or Cmin on Day 1 of study drugs on Cycles 1, 2, 3, 4, 5, 8, 9, 13, 21, then every 6 cycles while on treatment and at the End-of-Treatment visits. Cycles 
1 and 8 will have additional samples on days 2, 4, 8, and 15 (Cohort 1aD only) 
p. 
Antinuclear antibody (ANA) samples will be collected prior to dose at Cycles 1, 2, 3, 4, 5, 9, 13, 21, then every 6 cycles while on treatment and at End-of-Treatment Visits. Additional ANA reflex 
samples may be collected upon requested or as clinically indicated. Testing by indirect fluorescent antibody (IFA) will be performed as clinically indicated. If the titer is positive, erythrocyte 
sedimentation rate (ESR) and C-reactive protein (CRP) will be tested to confirm the result.  

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q. 
Cabiralizumab and nivolumab will both be administered by IV infusion over 30 minutes (± 5 minutes). If any Grade 3 or higher infusion reaction is observed during the proposed infusion rate of 
nivolumab 3 mg/kg over 30 minutes, the infusion rate will be extended to 60 minutes for all current and subsequent patients for the duration of this study. Nivolumab will be given first, with a 30-to 
60-minute rest, followed by cabiralizumab as a 30-minute infusion. 
r. 
Cabiralizumab + nivolumab study drug will be administered every 2 weeks in 14-day cycles and will continue until PD or unacceptable toxicity. 
s. 
These assessments are to be performed prior to each subsequent dose (with exceptions noted in Appendix C) for patients who continue treatment without signs of progressive disease or toxicity. 
t. 
Patients should be contacted every 12 (±2) weeks for survival status. Patients should have tumor scans 12 (±2) weeks, if tumor progression was not previously determined and/or use of subsequent 
anti-cancer therapy has not been initiated. Any new anti-cancer therapy should be documented. 

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Study Cycle 
Study Day 
Time Point 
Type of Sample 
15 (±5) minutes after 
infusion 
Cabiralizumab PK and Nivolumab PK (serum) 
4 (±1) hours after 
infusion 
Cabiralizumab PK (serum) 
Day 2 
24 (±6) hours after 
infusion 
Cabiralizumab PK (serum) 
Day 4 
72 (±12) hours after 
infusion 
Cabiralizumab PK (serum) 
Cytokine multiplex panel (serum) 
Selected serum markers (serum) 
CD14+/CD16+ monocytes (whole blood) 
Day 8 
168 (±24) hours after 
infusion 
Cabiralizumab PK (serum) 
Cytokine multiplex panel (serum) 
Selected serum markers (serum) 
CD14+/CD16+ monocytes (whole blood) 
Day 15 
(Cohort 1aD only) 
336 
 (±24) hours after 
infusion 
Cabiralizumab PK (serum) 
Cycles 5, 9, 13, 
21, then every 
6 cycles while 
on treatment 
Day 1 
Prior to infusion 
(within 4 hours) 
Cabiralizumab and Nivolumab PK (serum) 
Selected serum markers (serum) 
Cytokine multiplex panel (serum) 
ANA (serum)  
CD14+/CD16+ monocytes (whole blood)  
  
Cabiralizumab and Nivolumab ADA (serum)  
End-of-
Treatment 
Follow-up 
Period (28 [±7] 
days and 100 
[±7] days post-
last dose) 
Treatment 
discontinuation/PD 
Post completion of 
treatment course 
Biopsy tissue for patients who have documented 
disease progression (Day 28 post-last dose visit only) 
Cabiralizumab and Nivolumab PK (serum) 
Cabiralizumab and Nivolumab ADA (serum) 
Selected serum markers (serum) 
Cytokine multiplex panel (serum) 
ANA (serum) 
CD14+/CD16+ monocytes, (whole blood) 
 
Note that the nivolumab assessments listed above will not be performed for the Phase 1a monotherapy cohorts. 

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Appendix D: Sample Collection for PD Analyses 
• Tumor biopsy/tumor tissue samples 
– IHC analysis of selected biomarkers  
– Gene expression analysis 
– T-cell receptor clonality 
– Neo-antigen analysis 
• Skin biopsy samples 
– IHC analysis of selected biomarkers 
• Blood samples 
– Whole blood analyses 
 CD14+/CD16+ monocytes 
 
  
 DNA for SNP analysis 
– Serum analyses 
 PK of cabiralizumab 
 PK of nivolumab 
 ADA of cabiralizumab 
 ADA of nivolumab  
 ANA (if result is positive, check ANA reflex, ESR and CRP to confirm) 
 Selected serum markers 
 Serum cytokine multiplex 
 
 
 
 
 
 
 

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Appendix E: Biopsy Requirements  
Cohort 
Skin Biopsy Time-Point 
Tumor Biopsy Time-Point 
Pre-treatment 
On-treatment 
Post-
progression 
Pre-treatment 
On-treatment 
Post-
progression 
Prior to C3D1 Post-response 
Prior to C3D1 
Post-
response 
1aM1 
Required 
Required 
Optional 
Optional 
Required 
Required 
Optional 
Optional 
1aM2 
Required 
Required 
Optional 
Optional 
Required 
Required 
Optional 
Optional 
1aM3 
Required 
Required 
Optional 
Optional 
Required 
Required 
Optional 
Optional 
1aM4 
Required 
Required 
Optional 
Optional 
Required 
Required 
Optional 
Optional 
1aC1 
Required 
Required 
Optional 
Optional 
Required 
Required 
Optional 
Optional 
1aC2 
Required 
Required 
Optional 
Optional 
Required 
Required 
Optional 
Optional 
1aC3 
Required 
Required 
Optional 
Optional 
Required 
Required 
Optional 
Optional 
1aD 
Required 
Required 
Optional 
Optional 
Required 
Required 
Optional 
Optional 
1aE 
Required 
Required 
Optional 
Optional 
Required 
Required 
Optional 
Optional 
1b1 
Not Required 
Not Required 
Not Required 
Not Required 
Required for  
≥ 10 patients 
Required for  
≥ 10 patients 
Optional 
Optional 
1b2 
Not Required 
Not Required 
Not Required 
Not Required 
Required for  
≥ 10 patients 
Required for  
≥ 10 patients 
Optional 
Optional 
1b3 
Not Required 
Not Required 
Not Required 
Not Required 
Required for  
≥ 10 patients 
Required for 
≥10 patients 
Optional 
Optional 
1b4 
Not Required 
Not Required 
Not Required 
Not Required 
Required for  
≥ 10 patients 
Required for  
≥ 10 patients 
Optional 
Optional 
1b5 
Not Required 
Not Required 
Not Required 
Not Required 
Required for  
≥ 10 patients 
Required for  
≥ 10 patients 
Optional 
Optional 
1b6 
Not Required 
Not Required 
Not Required 
Not Required 
Required for  
≥ 10 patients 
Required for  
≥ 10 patients 
Optional 
Optional 
1b7 
Not Required 
Not Required 
Not Required 
Not Required 
Optional 
Optional 
Optional 
Optional 
Pre- and on-treatment C3D1 biopsies are required for a minimum of ten patients per cohort in Phase 1b (optional for Cohort 1b7). If available, tumor 
tissue obtained from procedures such as surgery may also be collected. 

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Appendix I: ECOG 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.