Conditions: Advanced Malignancies Metastatic Cancer
Keywords: cervical cancer endometrial cancer gastric cancer (stomach, esophageal, and gastroesophageal junction [GEJ]) hepatocellular carcinoma (HCC) melanoma Merkel cell carcinoma mesothelioma microsatellite instability-high (MSI-H) colorectal cancer (CRC) non-small cell lung cancer (NSCLC) ovarian cancer squamous cell carcinoma of the head and neck (SCCHN) small cell lung cancer (SCLC) renal cell carcinoma (RCC) triple-negative breast cancer (TNBC) urothelial carcinoma glucocorticoid-induced tumor necrosis factor receptor (GITR)
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 145
Healthy volunteers: no

Brief summary:
The purpose of this study is to determine the safety, tolerability, and efficacy of INCAGN01876 when given in combination with immune therapies in subjects with advanced or metastatic malignancies.

Detailed description:

Arms:
arm 1: Participants received INCAGN01876 1.0 milligrams per kilogram (mg/kg) administered intravenously (IV) every 2 weeks (Q2W) in combination with nivolumab 240 mg administered IV Q2W. arm 2: Participants received INCAGN01876 3.0 mg/kg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W. arm 3: Participants received INCAGN01876 5.0 mg/kg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W. arm 4: Participants received INCAGN01876 10.0 mg/kg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W. arm 5: Participants received INCAGN01876 1.0 mg/kg administered IV Q2W for a total of 2 doses as run-in, followed by INCAGN01876 1.0 mg/kg Q2W in combination with nivolumab 240 mg administered IV Q2W starting at Cycle 3. arm 6: Participants received INCAGN01876 1.0 mg/kg administered IV Q2W for a total of 2 doses as run-in, followed by INCAGN01876 1.0 mg/kg Q2W in combination with nivolumab 240 mg administered IV Q2W starting at Cycle 3. arm 7: Participants received INCAGN01876 5.0 mg/kg administered IV Q2W for a total of 2 doses as run-in, followed by INCAGN01876 5.0 mg/kg Q2W in combination with nivolumab 240 mg administered IV Q2W starting at Cycle 3. arm 8: Participants received INCAGN01876 1.0 mg/kg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV every 6 weeks (Q6W). arm 9: Participants received INCAGN01876 3.0 mg/kg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV Q6W. arm 10: Participants received INCAGN01876 5.0 mg/kg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV Q6W. arm 11: Participants received INCAGN01876 1.0 mg/kg administered IV Q2W in combination with nivolumab 3 mg/kg administered IV Q2W and ipilimumab 1 mg/kg administered IV Q6W. arm 12: Participants with programmed cell death protein/programmed cell death ligand 1 (PD-1/PD-L1) relapsed melanoma received INCAGN01876 300 mg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV Q6W. arm 13: Participants with gastric cancer (GC) received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W. arm 14: Participants with squamous cell carcinoma of the head and neck (SCCHN) received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W. arm 15: Participants with cervical cancer (CC) received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W. arm 16: Participants with PD-1/PD-L1 relapsed melanoma received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W. arm 17: Participants with gastric cancer, squamous cell carcinoma of the head and neck, cervical cancer, or PD-1/PD-L1 relapsed melanoma who had tumor lesions that were amenable to percutaneous biopsy received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Interventions: intervention 1: INCAGN01876 intervention 2: Nivolumab intervention 3: Ipilimumab
Intervention descriptions: intervention 1: In Phase 1 participants will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will be administered IV study drug at the recommended dose from Phase 1 (). intervention 2: Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group. intervention 3: Ipilimumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Protocol document:
Prot_000.pdf: 
Official Title: 
A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of 
INCAGN01876 in Combination With Immune Therapies in Subjects 
With Advanced or Metastatic Malignancies 
NCT Number: 
NCT03126110 
Document Date: 
Protocol Version 5: 22-January-2021 


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Protocol INCAGN 1876-201 Am 5 
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Clinical Study Protocol 
 
INCAGN 1876-201 
A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy 
of INCAGN01876 in Combination With Immune Therapies in 
Subjects With Advanced or Metastatic Malignancies 
 
 
Product: 
INCAGN01876 
IND Number: 
 
EudraCT Number: 
2016-004989-25 
Phase of Study: 
1/2 
Sponsor: 
Incyte Biosciences International Sàrl 
Route de la Corniche 1 
1066 Epalinges, Switzerland 
Original Protocol (Version 0): 
20 DEC 2016 
Amendment (Version) 1: 
12 JUN 2017 
Amendment (Version) 2: 
22 AUG 2017 
Amendment (Version) 3: 
18 DEC 2017 
Amendment (Version) 4: 
24 OCT 2018 
Amendment (Version) 5: 
22 JAN 2021 
 
This study will be performed in accordance with ethical principles that have their origin in the Declaration of 
Helsinki and conducted in adherence to the study Protocol, Good Clinical Practices as defined in Title 21 of the 
US Code of Federal Regulations Parts 11, 50, 54, 56, and 312, as well as ICH GCP consolidated guidelines (E6) and 
applicable regulatory requirements. 
 
The information in this document is confidential.  No part of this information may be duplicated, referenced, or 
transmitted in any form or by any means (electronic, mechanical, photocopy, recording, or otherwise) without the prior 
written consent of Incyte Biosciences International Sàrl. 


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INVESTIGATOR'S AGREEMENT 
I have read the INCAGN 1876-201 Protocol Amendment 5 (Version 5 dated 22 JAN 2021) and 
agree to conduct the study as outlined.  I agree to maintain the confidentiality of all information 
received or developed in connection with this Protocol. 
 
 
 
 
 
(Printed Name of Investigator) 
 
 
 
 
 
 
 
 
(Signature of Investigator) 
 
(Date) 
















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Study Population:  Key inclusion and exclusion criteria are noted below.  Full subject eligibility 
criteria are located in the body of the Protocol. 
Key Inclusion Criteria: 
• Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection 
with curative intent. 
• Phase 1:  Subjects with advanced or metastatic cervical cancer, endometrial cancer, gastric cancer 
(including stomach, esophageal, and GEJ), HCC, melanoma (excluding uveal melanoma), Merkel cell 
carcinoma, mesothelioma, MSI-H CRC, NSCLC, ovarian cancer, SCCHN, SCLC, RCC, TNBC, and 
urothelial carcinoma (or alternative tumor types with medical monitor approval). 
• Phase 1:  Subjects who have disease progression after treatment with available therapies that are 
known to confer clinical benefit, or who are intolerant to treatment, or who refuse standard treatment.  
There is no limit to the number of prior treatment regimens. 
• Phase 2:  Subjects with advanced or metastatic cervical cancer, gastric cancer (including stomach, 
esophageal, and GEJ), SCCHN, PD-1 refractory SCCHN, or PD-1 or PD-L1 relapsed melanoma. 
− For subjects with cervical cancer: should have histologically confirmed squamous cell carcinoma 
of the cervix. 
Note:  Should have received up to 2 prior therapy regimens for advanced or metastatic disease (not 
including neoadjuvant and/or adjuvant therapy).  Adjuvant regimens given within 6 months of 
screening would be counted as first-line therapy. 
Note:  Prior therapy should not have included an immune therapy (eg, anti–cytotoxic 
T-lymphocyte–associated protein 4 [CTLA-4], anti–programmed cell death protein 1 (PD-1), 
anti-programmed cell death protein ligand 1 (PD-L1), indoleamine 2,3-dioxygenase [IDO] 
inhibitors, tumor necrosis factor super family (TNFSF) agonists, or other antibodies or drugs 
specifically targeting T-cell costimulation or checkpoint pathways, etc).  
− For subjects with gastric cancer:  adenocarcinoma of the stomach, esophagus, or GEJ. 
Note:  Should have received only 1 prior chemotherapy regimen for advanced or metastatic disease 
(not including neoadjuvant and/or adjuvant therapy).  Adjuvant regimens given within 6 months of 
screening would be counted as first-line therapy. 
Note:  Prior therapy should not have included an immune therapy (eg, anti–CTLA-4, anti–PD-1, 
anti–PD-L1, IDO inhibitors, TNFSF agonists, or other antibodies or drugs specifically targeting 
T-cell costimulation or checkpoint pathways, etc). 
Note:  HER-2/neu status known and subjects with HER2/neu positive tumors should have 
documented disease progression on or after treatment containing trastuzumab or other 
HER2/neu-targeted therapy. 
− For subjects with SCCHN:  histologically confirmed squamous cell carcinoma of the oral cavity, 
oropharynx, hypopharynx, or larynx. 
Note:  Subjects with tumors that are adjacent to or invade major blood vessels, as shown 
unequivocally by imaging studies are not eligible for participation. 
Note:  Should consent to have tumor evaluated for HPV and Epstein-Barr virus (EBV) status of the 
tumor (per local institutional testing), or have documentation of HPV and EBV tumor status. 
Note:  Should have received only 1 prior chemotherapy regimen for advanced or metastatic disease 
(not including neoadjuvant and/or adjuvant therapy).  Adjuvant regimens given within 6 months of 
screening would be counted as first-line therapy.  Prior chemotherapy regimen should have been a 
platinum-containing regimen. 
Note (Stage 2 only):  Should have progressive disease per RECIST v1.1 during or within 6 months 
after treatment with a platinum-containing regimen.  The platinum-based therapy must be the last 
therapy the subject received before enrollment. 
Note:  Prior therapy should not have included an immune therapy (eg, anti–CTLA-4, anti–PD-1,  
anti–PD-L1, IDO inhibitors, TNFSF agonists, or other antibodies or drugs specifically targeting 
T-cell costimulation or checkpoint pathways, etc). 




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− Serum creatinine > 1.5 × institutional upper limit of normal (ULN), OR measured or calculated 
creatinine clearance < 50 mL/min for subjects with creatinine levels > 1.5 × ULN. 
− Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase ≥ 2.5 × ULN.  
− Total bilirubin ≥ 1.2 × ULN unless conjugated bilirubin ≤ ULN (conjugated bilirubin only needs to 
be tested if total bilirubin exceeds ULN).  If there is no institutional ULN, then direct bilirubin must 
be < 40% of total bilirubin.   
− International normalized ratio, prothrombin time, or activated partial thromboplastin time 
> 1.5 × ULN. 
• Prior treatment with any TNFSF agonist (eg, glucocorticoid-induced tumor necrosis factor receptor 
[GITR], OX40, 4-1BB/CD137, CD27, etc), for any indication. 
• Transfusion of blood products (including platelets or red blood cells) or administration of colony 
stimulating factors within 14 days before study Day 1. 
• Receipt of anticancer medications or investigational drugs within the following intervals before the 
first administration of study drug: 
− ≤ 14 days for chemotherapy, targeted small molecule therapy, or radiation therapy.   
Note:  Subjects must not have had radiation pneumonitis as a result of treatment.  A 1-week 
washout is permitted for palliative radiation to non–central nervous system (CNS) disease with 
medical monitor approval. 
Note:  Bisphosphonates and denosumab are permitted concomitant medications. 
− ≤ 28 days for prior immune therapy or persistence of active cellular therapy (ie, chimeric antigen 
receptor T-cell therapy; other cellular therapies must be discussed with medical monitor to 
determine eligibility). 
− ≤ 28 days for a prior monoclonal antibody used for anticancer therapy with the exception of 
denosumab. 
− ≤ 7 days for immune-suppressive–based treatment for any reason. 
Note:  Use of inhaled or topical steroids or corticosteroid use for radiographic procedures is 
permitted. 
Note:  Must not require chronic use of corticosteroids.  The use of physiologic corticosteroid 
replacement therapy may be approved after consultation with the medical monitor.   
− ≤ 28 days or 5 half-lives (whichever is longer) before the first dose for all other investigational 
agents or devices.  For investigational agents with long half-lives (eg, > 5 days), enrollment before 
the fifth half-life requires medical monitor approval. 
• Has not recovered to ≤ Grade 1 from toxic effects of prior therapy (including prior immune therapy) 
and/or complications from prior surgical intervention before starting therapy. 
Note:  Subjects with stable chronic conditions (≤ Grade 2) not expected to resolve (such as 
neuropathy and alopecia) are exceptions and may enroll. 
Note:  Subjects with a history of any grade immune-related ocular AE (eg, episcleritis, scleritis, 
uveitis) will be excluded. 
Note:  Subjects with a history of a Grade 3 or higher immune-related AE from prior immunotherapies 
are excluded from the dose escalation portion of the study. 
• Active autoimmune disease that required systemic treatment in the past (ie, with use of disease 
modifying agents, corticosteroids, or immunosuppressive drugs). 
Note:  Subjects who have not required systemic treatment in the past 2 years should discuss their case 
with medical monitor to determine eligibility. 
Note:  Subjects with hyper/hypothyroidism, vitiligo, controlled asthma, Type I diabetes, Graves' 
disease, or Hashimoto's disease are eligible to participate. 
Note:  Replacement and symptomatic therapies (eg, levothyroxine, insulin, or physiologic 
corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) are not considered a 
form of systemic treatment and are allowed. 


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• Known active CNS metastases and/or carcinomatous meningitis. 
Note:  Subjects with previously treated brain metastases may participate provided that they are stable 
(without evidence of progression by imaging for at least 28 days before the first dose of study drug 
and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain 
metastases or CNS edema, and have not required steroids for at least 7 days before the first dose of 
study drug. 
• Evidence of active, noninfectious pneumonitis or history of interstitial lung disease. 
• History or presence of an abnormal electrocardiogram that, in the investigator's opinion, is clinically 
meaningful.   
• Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation. 
• Known history of human immunodeficiency virus (HIV; HIV 1/2 antibodies). 
INCAGN01876, Dosage, and Mode of Administration:   
Phase 1 and Phase 2:  INCAGN01876 will be administered IV over a 30-minute period on Day 1 of 
each Q2W (ie, 14 days) cycle.  During Phase 2, fixed doses of INCAGN01876 (comparable to or less 
than the MTD/PAD determined during dose escalation), may also be explored.  INCAGN01876 will be 
the first drug administered, followed by a 30-minute wait before starting infusion with the next agent.  
Subjects will continue to receive INCAGN01876 as long as they are deriving benefit and have not met 
any of the Protocol-defined conditions for treatment withdrawal, or for up to 24 months from the first 
dose of study treatment, whichever occurs first. 
Reference Therapies, Dosage, and Mode of Administration: 
Dosage and Mode of Administration for Nivolumab:   
In the doublet Treatment Groups A, B, F, and H, nivolumab will be administered IV per the package 
insert or institutional guidelines at a dose of 240 mg Q2W (eg, 14 days).   
In the triplet Treatment Groups D, E, J, and L, nivolumab will be administered IV per the package 
insert or institutional guidelines at a dose of 3 mg/kg Q2W (eg, 14 days).   
In the concurrent dosing Treatment Groups A, D, F, and J, nivolumab dosing will begin on Cycle 1 
Day 1. 
In the sequenced dosing Treatment Groups B, E, H, and L, nivolumab dosing will begin on Cycle 3 
Day 1. 
Nivolumab will be administered at least 30 minutes after the infusion of INCAGN01876 (when 
applicable).  Subjects will continue to receive nivolumab as long as they are deriving benefit and have 
not met any of the Protocol-defined conditions for treatment withdrawal, or for up to 24 months from 
the first dose of study treatment, whichever occurs first. 
Dosage and Mode of Administration for Ipilimumab: 
Ipilimumab will be administered IV per the package insert or institutional guidelines to subjects in 
Treatment Groups C, C2 (Phase 2 expansion), D, E, J, and L, at a dose of 1 mg/kg Q6W (eg, 42 days).  
In the concurrent dosing Treatment Groups C, C2, D, and J, ipilimumab dosing will begin on Cycle 1 
Day 1.  In the sequenced dosing Treatment Groups E and L, ipilimumab dosing will begin on Cycle 3 
Day 1. 
Ipilimumab will be administered at least 30 minutes after the infusion of INCAGN01876 (when 
administered on the same day).  Ipilimumab will always be administered after INCAGN01876 and 
nivolumab.  Subjects will continue to receive ipilimumab as long as they are deriving benefit and have 
not met any of the Protocol-defined conditions for treatment withdrawal, or for up to 24 months from 
the first dose of study treatment, whichever occurs first. 
At the sponsor's discretion, once the MTD or PAD of INCAGN01876 has been established with 
ipilimumab at 1 mg/kg Q6W (eg, 42 days), a higher dose of ipilimumab at 3 mg/kg Q6W (eg, 42 days) 
and/or 3 mg/kg Q3W (eg, 21 days) for 4 doses may be tested.   


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Study Schedule/Procedures:   
Subjects will have regularly scheduled study visits at the clinical site on Day 1 of each cycle.  
Additional study visits may be required during some cycles to monitor for safety, efficacy
.  Study visits are as follows: 
Screening:  Up to 28 days before enrollment.  Screening will begin at the time that the subject signs 
the informed consent and will continue until the date that the subject is enrolled in the study (Cycle 1 
Day 1). 
Cycle 1 and Cycle 6:  Day 1 and Day 8 (± 1 day). 
All other treatment cycles:  Day 1 (± 3 days). 
Efficacy assessments:  Every 8 weeks (± 7 days).  After 12 months, efficacy assessments will occur 
every 12 weeks (± 7 days) until disease progression is determined. 
End of treatment:  ± 3 days of withdrawal from study. 
Safety follow-up:  30 days (+ 7 days) and 60 days (+ 7 days) after the last dose of study treatment.  
Note:  As of Protocol Amendment 5, these safety follow-up visits will include AE and concomitant 
medication assessment only and may be completed remotely (such as by televisit). 
Disease follow-up:  Subjects who discontinue treatment for reasons other than disease progression will 
continue to be assessed every 8 weeks (± 7 days) for their disease status during the follow-up period 
and should continue to have tumor assessments until a new cancer therapy is started, disease 
progression, death, the end of the study, or the subject withdraws consent. 
Note:  As of Protocol Amendment 5, no further disease follow-up assessments will be required beyond 
the last safety follow-up visit. 
Survival follow-up:  Once a subject has confirmed disease progression or starts a new anticancer 
therapy, the subject moves into the survival follow-up period and should be contacted every 12 weeks 
from the last dose of treatment for survival follow-up.  This follow-up may occur through a phone call, 
email, or visit by the subject or the subject's caregiver. 
Note:  As of Protocol Amendment 5, no further survival follow-up assessments will be required 
beyond the last safety follow-up visit. 
Estimated Duration of Participation:  Subjects may continue on treatment as long as they are 
receiving benefit and do not meet withdrawal criteria, or for up to 24 months from the first dose of 
treatment, whichever occurs first.  All subjects will be followed for survival.  Study participation, 
including post-treatment follow-up is expected to average approximately 12 to 18 months per 
individual subject. 
Estimated Number of Subjects: 
• Phase 1 Dose Escalation – Approximately 90 to 270 evaluable subjects. 
Note:  The minimum number of subjects assumes that the starting dose is 0.1 mg/kg; however, fewer 
subjects would be enrolled if a higher starting dose is used based on available safety data from the 
monotherapy study INCAGN 1876-101. 
Note:  The maximum number of subjects assumes that DLTs are observed in all dose cohorts to a 
maximum of 9 subjects per cohort across all treatment groups. 
• Phase 2 Stage 1 – Approximately 264 evaluable subjects. 
• 
 
• Phase 2 Stage 2 – Approximately 455 evaluable subjects. 
• Phase 2 Expansion Stage (PD-1 refractory SCCHN cohort only) – Approximately 20 evaluable 
subjects 
Note:  Assumes that all treatment groups and all tumor types proceed to Stage 2 and expansion stage 
(for PD-1 refractory SCCHN cohort only). 


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Coordinating Principal Investigator:  
 
 
Statistical Methods:   
In Phase 2, a Simon 2-stage design will be run for the cervical cancer, gastric cancer, SCCHN and 
PD-1/PD-L1 relapsed melanoma cohorts within a given doublet or triplet treatment group.  The 
planned Simon 2-stage designs are summarized in Table S5, assuming a 1-sided Type I error of 0.05 
and power of 85%.  Each Simon 2-stage design will have a stopping rule to allow early termination of 
a particular tumor type within the given drug combination at the end of Stage 1 if there is insufficient 
response observed (calculated response rate < p0), while enrolling enough subjects to predict possible 
target responses (≥ p1) worthy of cohort expansion and potentially further evaluation in future studies. 
Table S5:  Planned Simon 2-Stage Designs for Phase 2 
Indication 
Combination 
r1 
n1 
r 
n2 
n 
p0 
p1 
SCCHN 
GITR + Nivo 
3 
16 
10 
30 
46 
15% 
35% 
Gastric 
GITR + Nivo 
3 
16 
10 
30 
46 
15% 
35% 
Cervical 
GITR + Nivo 
4 
17 
14 
34 
51 
20% 
40% 
Relapsed melanoma 
GITR + Nivo 
2 
20 
8 
30 
50 
10% 
25% 
Relapsed melanoma 
GITR + Ipi 
2 
20 
8 
30 
50 
10% 
25% 
SCCHN 
GITR + Nivo + Ipi 
5 
18 
17 
32 
50 
25% 
45% 
Gastric 
GITR + Nivo + Ipi 
5 
18 
17 
32 
50 
25% 
45% 
Cervical 
GITR + Nivo + Ipi 
7 
21 
19 
27 
48 
30% 
50% 
r1:  If r1 or fewer responses are observed during Stage 1, the study cohort is stopped early for futility. 
n1:  Number of subjects initially enrolled in the Stage 1. 
n2:  Number of subjects enrolled in the Stage 2. 
r:  If r or fewer responses are observed by the end of Stage 2, then no further investigation of the drug combination is 
warranted in the selected tumor type. 
n:  Total number of subjects. 
p0:  Insufficient response rate. 
p1:  Target response rate. 
For the PD-1 refractory SCCHN cohort in doublet Treatment Group F, a Simon 2-stage design with an 
expansion stage, summarized in Table S6, will be used.  With this 3-stage design, the 1-sided Type I 
error is 0.0231, and the power is approximately 88%.  The PD-1 refractory SCCHN cohort will be 
terminated early for futility at the end of Stage 1 or Stage 2 if there is insufficient response observed.  
At the end of the expansion stage, if there is sufficient response observed, the doublet schedule for the 
PD-1 refractory SCCHN cohort will be declared promising for further investigation; otherwise it is 
considered nonpromising. 
Table S6:  Planned Simon 2-Stage Design With Expansion Stage for PD-1 refractory SCCHN 
Cohort in Phase 2 
Indication 
Combination 
r1 
n1 
r2 
n2 
r 
n3 
n 
p0 
p1 
PD-1 refractory SCCHN 
GITR + Nivo 
0 
12 
3 
25 
6 
20 
57 
5% 
20% 
Note:  The definitions of p0, p1, r1, n, n1, and n2 are the same as those in Table S5. 
r2:  If r2 or fewer responses are observed by the end of Stage 2, the study cohort is stopped early for futility. 
r:  If r or fewer responses are observed by the end of expansion stage, then no further investigation of the drug combination is 
warranted in the study cohort. 
n3:  Number of subjects enrolled in the expansion stage. 


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Integrated Futility Analysis:  
For the cervical cancer, gastric cancer and SCCHN cohorts, when each subject enrolls in Phase 2, an 
integrated analysis of tumor and dosing strategies (including concurrent dosing and INCAGN01876 
run-in Q2W for 2 doses followed by INCAGN01876 Q2W in combination with the combining drug[s]) 
will be conducted based on Simon et al (2016).  Tumor types within a dosing strategy will jointly be 
analyzed using a Bayesian model before allowing sharing of information across tumor types.  Similar 
sharing will be applied separately for dosing strategies across tumor types.  The purpose of the 
integrated Bayesian analysis is to determine if INCAGN01876 is active within any of the given dosing 
strategies, given tumor types, or given dosing strategy-tumor type combinations.  Enrollment in a 
dosing strategy-tumor type combination will be terminated if the probability of success is not above 
20% for both analysis approaches.  Collection of response data will be based on investigator 
assessments entered into an interactive response technology system and analyzed separately from the 
clinical database.  Additional information regarding the futility analysis is detailed in the full Protocol. 
The proposed designs for each tumor type and treatment combination will be used for any planned 
Simon 2-stage design in the treatment combination (including concurrent and sequential dosing).  Each 
Simon 2-stage design is set up to have a 1-sided Type I error of 0.05 and power of 85%.  The response 
rates for each tumor type within a drug combination will be estimated with 95% confidence intervals.  
Formal safety reviews, to be held at least every 6 months, will be conducted to review efficacy and 
safety data. 




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1.5.2.1. 
Cervical Carcinoma ....................................................................................................37 
1.5.2.2. 
Gastric Cancer ............................................................................................................38 
1.5.2.3. 
Squamous Cell Carcinoma of the Head and Neck ......................................................38 
1.5.2.4. 
Subjects With Squamous Cell Carcinoma of the Head and Neck Who Have 
Progressed on Prior Treatment With an Anti–PD-1 Therapy .....................................39 
1.5.2.5. 
Subjects With Melanoma Who Have Relapsed After Prior Treatment With 
an Anti–PD-1 or Anti–PD-L1 Therapy ......................................................................40 
1.5.3. 
Rationale for Dose and Schedule of Combination Therapies .....................................40 
1.5.3.1. 
Rationale for Fixed Dosing of INCAGN01876 ..........................................................41 
 
42 
1.5.4.1. 
Efficacy Endpoints ......................................................................................................42 
2. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................44 
2.1. 
Study Objectives .........................................................................................................44 
2.1.1. 
Primary Objectives .....................................................................................................44 
2.1.2. 
Secondary Objectives .................................................................................................44 
 
44 
2.2. 
Study Endpoints ..........................................................................................................45 
2.2.1. 
Primary Endpoints ......................................................................................................45 
2.2.2. 
Secondary Endpoints ..................................................................................................45 
 
45 
3. 
SUBJECT ELIGIBILITY ...........................................................................................46 
3.1. 
Subject Inclusion Criteria ...........................................................................................46 
3.2. 
Subject Exclusion Criteria ..........................................................................................49 
4. 
INVESTIGATIONAL PLAN .....................................................................................52 
4.1. 
Overall Study Design ..................................................................................................52 
4.1.1. 
Phase 1 – Dose Escalation ..........................................................................................53 
4.1.1.1. 
Doublet Immune Therapy Combinations ...................................................................54 
4.1.1.2. 
Triplet Immune Therapy Combinations .....................................................................56 
4.1.2. 
Phase 2 – Dose Expansion ..........................................................................................58 
4.2. 
Measures Taken to Avoid Bias ...................................................................................60 
4.3. 
Number of Subjects ....................................................................................................60 
4.3.1. 
Planned Number of Subjects ......................................................................................60 
4.3.2. 
Replacement of Subjects .............................................................................................60 


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4.4. 
Duration of Treatment and Subject Participation .......................................................60 
4.5. 
Overall Study Duration ...............................................................................................61 
4.6. 
Study Termination ......................................................................................................61 
5. 
TREATMENT ............................................................................................................62 
5.1. 
Treatment Assignment ................................................................................................62 
5.1.1. 
Subject Numbering and Treatment Assignment .........................................................62 
5.1.2. 
Randomization and Blinding ......................................................................................62 
5.2. 
Study Drugs ................................................................................................................62 
5.2.1. 
INCAGN01876 ...........................................................................................................62 
5.2.1.1. 
Description and Administration ..................................................................................62 
5.2.1.2. 
Supply, Packaging, and Labeling ...............................................................................63 
5.2.1.3. 
INCAGN01876 Storage ..............................................................................................63 
5.2.2. 
Standard Immune Therapies .......................................................................................63 
5.2.2.1. 
Nivolumab ..................................................................................................................63 
5.2.2.2. 
Ipilimumab ..................................................................................................................64 
5.3. 
Treatment Compliance ................................................................................................64 
5.3.1. 
Treatment Compliance of INCAGN01876, Nivolumab, and Ipilimumab .................64 
5.4. 
Treatment Interruptions and Adjustments ..................................................................65 
5.4.1. 
Dose Modifications .....................................................................................................65 
5.4.2. 
Dose-Limiting Toxicity and Determination of Maximum Tolerated Dose ................65 
5.4.3. 
Management of Dose-Limiting Toxicities or Other Urgent Situations ......................67 
5.4.4. 
Follow-Up of Dose-Limiting Toxicities .....................................................................67 
5.4.5. 
Procedures for Cohort Review and Dose Escalation ..................................................67 
5.4.6. 
Criteria and Procedures for Dose Interruptions of Study Drug ..................................67 
5.4.7. 
Management of Immune-Related Adverse Events .....................................................68 
5.4.8. 
Management of Infusion Reactions ............................................................................69 
5.4.9. 
Criteria for Permanent Discontinuation of Study Drug ..............................................71 
5.5. 
Withdrawal of Subjects From Study Treatment .........................................................71 
5.5.1. 
Withdrawal Criteria ....................................................................................................71 
5.5.2. 
Withdrawal Procedures ...............................................................................................72 
5.6. 
Concomitant Medications ...........................................................................................73 
5.6.1. 
Permitted Medications ................................................................................................73 
5.6.2. 
Restricted Medications ...............................................................................................73 


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5.6.3. 
Prohibited Medications ...............................................................................................73 
6. 
STUDY ASSESSMENTS ..........................................................................................75 
6.1. 
Screening ....................................................................................................................80 
6.2. 
Treatment ....................................................................................................................81 
6.3. 
End of Treatment ........................................................................................................81 
6.4. 
Follow-Up ...................................................................................................................81 
6.4.1. 
Safety Follow-Up ........................................................................................................81 
6.4.2. 
Disease Status Follow-Up ...........................................................................................81 
6.4.3. 
Survival Follow-Up ....................................................................................................82 
6.5. 
End of Study ...............................................................................................................82 
6.6. 
Unscheduled Visits .....................................................................................................82 
7. 
CONDUCT OF STUDY ASSESSMENTS AND PROCEDURES ...........................83 
7.1. 
Administration of Informed Consent Form ................................................................83 
7.2. 
Interactive Response Technology System Procedure .................................................83 
7.3. 
Demography and Medical History ..............................................................................84 
7.3.1. 
Demographics and General Medical History .............................................................84 
7.3.2. 
Disease Characteristics and Treatment History ..........................................................84 
7.4. 
Prior and Concomitant Medications and Procedures ..................................................84 
7.5. 
Poststudy Anticancer Therapy Status .........................................................................84 
7.6. 
Safety Assessments .....................................................................................................84 
7.6.1. 
Adverse Events ...........................................................................................................85 
7.6.2. 
Physical Examinations ................................................................................................85 
7.6.2.1. 
Comprehensive Physical Examination .......................................................................85 
7.6.2.2. 
Targeted Physical Examination ..................................................................................85 
7.6.3. 
Vital Signs ..................................................................................................................85 
7.6.4. 
Electrocardiograms .....................................................................................................85 
7.6.5. 
Laboratory Assessments .............................................................................................86 
7.6.5.1. 
Pregnancy Testing ......................................................................................................86 
7.6.5.2. 
Hepatitis Screening Tests ...........................................................................................86 
7.7. 
Efficacy Assessments .................................................................................................87 
7.7.1. 
Modified RECIST v1.1 Assessment Disease .............................................................87 
7.7.1.1. 
Tumor Imaging ...........................................................................................................88 
7.8. 
Performance and Quality-of-Life Assessments ..........................................................89 




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9.2. 
Selection of Sample Size ..........................................................................................102 
9.2.1. 
Sample Size for Phase 1 ...........................................................................................102 
9.2.2. 
Sample Size for Phase 2 ...........................................................................................103 
9.3. 
Level of Significance ................................................................................................105 
9.4. 
Statistical Analyses ...................................................................................................105 
9.4.1. 
Efficacy Analyses .....................................................................................................105 
9.4.1.1. 
Primary Efficacy Analyses .......................................................................................105 
9.4.1.2. 
Secondary Efficacy Analyses ...................................................................................106 
9.4.2. 
Safety Analyses ........................................................................................................106 
9.4.2.1. 
Adverse Events .........................................................................................................106 
9.4.2.2. 
Clinical Laboratory Tests .........................................................................................106 
9.4.2.3. 
Vital Signs ................................................................................................................107 
9.4.2.4. 
Electrocardiograms ...................................................................................................107 
 
107 
 
108 
9.5. 
Analyses for the Data Monitoring Committee ..........................................................108 
9.6. 
Interim Analysis ........................................................................................................108 
9.6.1. 
Simon 2-Stage Design and Simon 2-Stage Design With an Expansion Stage .........108 
9.6.2. 
Integrated Bayesian Futility Analysis .......................................................................109 
10. 
ETHICAL CONSIDERATIONS AND ADMINISTRATIVE 
PROCEDURES ........................................................................................................110 
10.1. 
Investigator Responsibilities .....................................................................................110 
10.1.1. 
Identification of the Coordinating Principal Investigator .........................................111 
10.2. 
Accountability, Handling, and Disposal of Study Drug ...........................................111 
10.3. 
Data Management .....................................................................................................112 
10.4. 
Data Privacy and Confidentiality of Study Records .................................................112 
10.5. 
Financial Disclosure .................................................................................................113 
10.6. 
Publication Policy .....................................................................................................113 
10.7. 
Study and Site Closure..............................................................................................114 
11. 
REFERENCES .........................................................................................................115 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS .............................................................................121 


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APPENDIX B. PROCEDURES AND SUPPORTIVE CARE GUIDELINES FOR 
SUBJECTS EXHIBITING IMMUNE-RELATED ADVERSE EVENTS ..............122 
APPENDIX C. PROTOCOL AMENDMENT SUMMARY OF CHANGES ..........................128 
 




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LIST OF FIGURES 
Figure 1: 
Overall Study Design ..................................................................................................53 
Figure 2: 
Dosing Figure for Treatment Group A (INCAGN01876 + Nivolumab) ....................55 
Figure 3: 
Dosing Figure for Treatment Group B (INCAGN01876 Sequenced Dosing + 
Nivolumab) .................................................................................................................55 
Figure 4: 
Dosing Figure for Treatment Group C (INCAGN01876 + Ipilimumab) ...................56 
Figure 5: 
Dosing Figure for Treatment Group D (INCAGN01876 + Nivolumab + 
Ipilimumab) ................................................................................................................57 
Figure 6: 
Dosing Figure for Treatment Group E (INCAGN01876 Sequenced Followed 
by Concurrent Dosing + Nivolumab + Ipilimumab) ..................................................58 
 


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LIST OF ABBREVIATIONS 
The following abbreviations and special terms are used in this clinical study Protocol. 
Abbreviation 
Definition 
ADA 
antidrug antibody 
ADCC 
antibody-dependent cell-mediated cytotoxicity 
ADCP 
antibody-dependent cell-mediated phagocytosis 
AE 
adverse event 
AGM 
African green monkey 
anti-HBc 
anti-hepatitis B core 
aPTT 
activated partial thromboplastin time 
CFR 
Code of Federal Regulations 
CNS 
central nervous system 
CR 
complete response 
CRC 
colorectal cancer 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTLA-4 
cytotoxic T-lymphocyte−associated protein 4 
DLT 
dose-limiting toxicity 
DNA 
deoxyribonucleic acid 
DOR 
duration of response 
EBV 
Epstein-Barr virus 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
ECOG 
Eastern Cooperative Oncology Group  
EOT 
end of treatment 
Fc 
fragment, crystallizable 
FcγR 
Fc-gamma receptor 
FDA 
Food and Drug Administration 
Foxp3 
forkhead box P3 
GCP 
Good Clinical Practice 
GEJ 
gastroesophageal junction 
GI 
gastrointestinal 
GITR 
glucocorticoid-induced tumor necrosis factor receptor 


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Abbreviation 
Definition 
GITRL 
glucocorticoid-induced tumor necrosis factor receptor ligand 
HCC 
hepatocellular carcinoma 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HIV 
human immunodeficiency virus 
HPV 
human papillomavirus 
ICF 
informed consent form  
ICH 
International Conference on Harmonization 
IDO 
indoleamine 2,3-dioxygenase 
IEC 
independent ethics committee 
IL 
interleukin 
INR 
international normalized ratio 
Ipi 
ipilimumab 
irAE 
immune-related adverse event 
IRB 
institutional review board 
IRT 
interactive response technology 
IV 
intravenous 
mAb 
monoclonal antibody 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMR 
mismatch repair 
mRECIST 
modified Response Evaluation Criteria in Solid Tumors 
MRI 
magnetic resonance imaging 
MSI 
microsatellite instability 
MSI-H 
microsatellite instability-high 
MTD 
maximum tolerated dose 
NFκB 
nuclear factor kappa-light-chain-enhancer of activated B cells 
Nivo 
nivolumab 
NSAID 
nonsteroidal anti-inflammatory drug 
NSCLC 
non–small cell lung cancer 
ORR 
objective response rate 


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Abbreviation 
Definition 
OS 
overall survival 
PAD 
pharmacologically active dose 
 
  
PD-1 
programmed cell death protein 1 
PD-L1 
programmed cell death protein ligand 1 
PFS 
progression-free survival 
 
 
PoS 
probability of success  
PR 
partial response 
PT 
prothrombin time 
Q2W 
every 2 weeks 
RCC 
renal cell carcinoma 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RNA 
ribonucleic acid 
RP2D 
recommended Phase 2 dose 
SAE 
serious adverse event 
SCCHN 
squamous cell carcinoma of the head and neck 
SCLC 
small cell lung cancer 
SD 
stable disease 
TCR 
T-cell receptor 
TEAE 
treatment-emergent adverse event 
 
 
 
 
TNBC 
triple-negative breast cancer 
TNF 
tumor necrosis factor 
TNFR 
tumor necrosis factor receptor 
TNFRSF 
tumor necrosis factor receptor super family 
TNFSF 
tumor necrosis factor super family 
 
 
ULN 
upper limit of normal 




































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3. 
SUBJECT ELIGIBILITY 
Deviations from eligibility criteria are not allowed because they can potentially jeopardize the 
scientific integrity of the study, regulatory acceptability, and/or subject safety.  Therefore, 
adherence to the criteria as specified in the Protocol is essential. 
3.1. 
Subject Inclusion Criteria 
A subject who meets all of the following criteria may be included in the study: 
1. Men and women, aged 18 or older. 
2. Willingness to provide written informed consent for the study. 
3. Locally advanced or metastatic disease; locally advanced disease must not be amenable 
to resection with curative intent. 
4. Phase 1:  Subjects with advanced or metastatic cervical cancer, endometrial cancer, 
gastric cancer (including stomach, esophageal, and GEJ), HCC, melanoma (excluding 
uveal melanoma), Merkel cell carcinoma, mesothelioma, MSI-H CRC, NSCLC, ovarian 
cancer, SCCHN, SCLC, RCC, TNBC, and urothelial carcinoma (or alternative tumor 
types with medical monitor approval). 
5. Phase 1:  Subjects who have disease progression after treatment with available therapies 
that are known to confer clinical benefit, or who are intolerant to treatment, or who refuse 
standard treatment.  There is no limit to the number of prior treatment regimens. 
6. Phase 2:  Subjects with advanced or metastatic cervical cancer, gastric cancer (including 
stomach, esophageal, and GEJ), SCCHN, PD-1 refractory SCCHN, or PD-1 or PD-L1 
relapsed melanoma.  
a. For subjects with cervical cancer:  should have documented histologically 
confirmed squamous cell carcinoma of the cervix. 
Note:  Should have received up to 2 prior therapy regimens for advanced or 
metastatic disease (not including neoadjuvant and/or adjuvant therapy).  Adjuvant 
regimens given within 6 months of screening would be counted as first-line therapy. 
Note:  Prior therapy should not have included an immune therapy (eg, anti–CTLA-4, 
anti–PD-1, anti–PD-L1, IDO inhibitors, TNFSF agonists, or other antibodies or drugs 
specifically targeting T-cell costimulation or checkpoint pathways, etc). 
b. For subjects with gastric cancer:  adenocarcinoma of the stomach, esophagus, or 
GEJ. 
Note:  Should have received only 1 prior chemotherapy regimen for advanced or 
metastatic disease (not including neoadjuvant and/or adjuvant therapy).  Adjuvant 
regimens given within 6 months of screening would be counted as first-line therapy. 
Note:  Prior therapy should not have included an immune therapy (eg, anti–CTLA-4, 
anti–PD-1, anti–PD-L1, IDO inhibitors, TNFSF agonists, or other antibodies or drugs 
specifically targeting T-cell costimulation or checkpoint pathways, etc). 
Note:  HER-2/neu status known and subjects with HER2/neu positive tumors should 
have documented disease progression on or after treatment containing trastuzumab or 
other HER2/neu-targeted therapy. 
c. For subjects with SCCHN:  histologically confirmed squamous cell carcinoma of 
the oral cavity, oropharynx, hypopharynx, or larynx. 






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3.2. 
Subject Exclusion Criteria 
A subject who meets any of the following criteria will be excluded from the study: 
1. Laboratory and medical history parameters not within the Protocol-defined range.  If the 
screening laboratory tests below were conducted > 7 days before treatment initiation, 
then the tests must be repeated and eligibility confirmed before study drug administration 
on Cycle 1 Day 1. 
a. Absolute neutrophil count < 1.0 × 109/L. 
b. Platelets < 75 × 109/L. 
c. Hemoglobin < 9 g/dL or < 5.6 mmol/L. 
d. Serum creatinine > 1.5 × institutional ULN, OR measured or calculated creatinine 
clearance (glomerular filtration rate can also be used in place of creatinine or 
creatinine clearance) < 50 mL/min for subjects with creatinine levels > 1.5 × ULN. 
e. Aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase 
≥ 2.5 × ULN. 
Note:  Subjects with 1) bone metastases and 2) no hepatic parenchymal metastases on 
screening radiographic examinations may enroll if the alkaline phosphatase is 
≤ 5 × ULN.  Subjects with 1) bone metastases and/or 2) hepatic parenchymal 
metastases on screening radiographic examinations may enroll if the alkaline 
phosphatase is ≤ 5 × ULN only with medical monitor approval. 
f. Total bilirubin ≥ 1.2 × ULN unless conjugated bilirubin ≤ ULN (conjugated bilirubin 
only needs to be tested if total bilirubin exceeds ULN).  If there is no institutional 
ULN, then direct bilirubin must be < 40% of total bilirubin.   
g. INR, PT, or activated partial thromboplastin time > 1.5 × ULN. 
2. Prior treatment with any TNFSF agonist (eg, GITR, OX40, 4-1BB/CD137, CD27, etc), 
for any indication. 
3. Transfusion of blood products (including platelets or red blood cells) or administration of 
colony stimulating factors (including granulocyte colony–stimulating factor, granulocyte 
macrophage colony–stimulating factor, or recombinant erythropoietin) within 14 days 
before study Day 1. 
4. Receipt of anticancer medications or investigational drugs within the following intervals 
before the first administration of study drug: 
a. ≤ 14 days for chemotherapy, targeted small molecule therapy, or radiation therapy.   
Note:  Subjects must not have had radiation pneumonitis as a result of treatment.  A 
1-week washout is permitted for palliative radiation to non–CNS disease with 
medical monitor approval. 
Note:  Bisphosphonates and denosumab are permitted concomitant medications. 
b. ≤ 28 days for prior immune therapy or persistence of active cellular therapy (ie, 
chimeric antigen receptor T-cell therapy; other cellular therapies must be discussed 
with medical monitor to determine eligibility). 
c. ≤ 28 days for a prior mAb used for anticancer therapy with the exception of 
denosumab. 


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d. ≤ 7 days for immune-suppressive–based treatment for any reason. 
Note:  Use of inhaled or topical steroids or corticosteroid use for radiographic 
procedures is permitted. 
Note:  Must not require chronic use of corticosteroids.  The use of physiologic 
corticosteroid replacement therapy may be approved after consultation with the 
medical monitor. 
e. ≤ 28 days or 5 half-lives (whichever is longer) before the first dose for all other 
investigational agents or devices.  For investigational agents with long half-lives 
(eg, > 5 days), enrollment before the fifth half-life requires medical monitor approval. 
5. Has not recovered to ≤ Grade 1 from toxic effects of prior therapy (including prior 
immune therapy) and/or complications from prior surgical intervention before starting 
therapy 
Note:  Subjects with stable chronic conditions (≤ Grade 2) not expected to resolve (such 
as neuropathy and alopecia) are exceptions and may enroll. 
Note:  Subjects with a history of any grade immune-related ocular AE (eg, episcleritis, 
scleritis, uveitis) will be excluded. 
Note:  Subjects with a history of a Grade 3 or higher immune-related AE from prior 
immunotherapies are excluded from the dose escalation portion of the study. 
6. Receipt of a live vaccine within 30 days of planned start of study therapy. 
Note:  Examples of live vaccines include, but are not limited to, the following:  measles, 
mumps, rubella, chicken pox/zoster, yellow fever, rabies, Bacillus Calmette–Guérin, and 
typhoid vaccine.  Seasonal influenza vaccines for injection are generally killed virus 
vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live 
attenuated vaccines and are not allowed. 
7. Current use of prohibited medication as described in Section 5.6.3. 
8. Active autoimmune disease that required systemic treatment in the past (ie, with use of 
disease modifying agents, corticosteroids, or immunosuppressive drugs). 
Note:  Subjects who have not required systemic treatment in the past 2 years should 
discuss their case with medical monitor to determine eligibility. 
Note:  Subjects with hyper/hypothyroidism, vitiligo, controlled asthma, Type I diabetes, 
Graves' disease, or Hashimoto's disease are eligible to participate. 
Note:  Replacement and symptomatic therapies (eg, levothyroxine, insulin, or 
physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) 
are not considered a form of systemic treatment and are allowed. 
9. Known active CNS metastases and/or carcinomatous meningitis. 
Note:  Subjects with previously treated brain metastases may participate provided that 
they are stable (without evidence of progression by imaging for at least 28 days before 
the first dose of study drug and any neurologic symptoms have returned to baseline), 
have no evidence of new or enlarging brain metastases or CNS edema, and have not 
required steroids for at least 7 days before the first dose of study drug. 


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10. Known additional malignancy that is progressing or requires active treatment, or history 
of other malignancy within 2 years of study entry with the exception of cured basal cell 
or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial 
neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, 
or cancers from which the subject has been disease-free for > 1 year, after treatment with 
curative intent. 
11. Evidence of active, noninfectious pneumonitis or history of interstitial lung disease. 
12. Clinically significant or uncontrolled cardiac disease, including unstable angina, acute 
myocardial infarction within 6 months from Day 1 of study drug administration, New 
York Heart Association Class III or IV congestive heart failure, and arrhythmia not 
controlled with therapy unless approved by medical monitor. 
13. History or presence of an abnormal ECG that, in the investigator's opinion, is clinically 
meaningful.  Subjects with screening QTc interval > 470 milliseconds (corrected by 
Fridericia) are excluded, unless approved by the medical monitor.  In the event that a 
single QTc is > 470 milliseconds, the subject may enroll if the average QTc for the 
3 ECGs is < 470 milliseconds.  For subjects with an intraventricular conduction delay 
(QRS interval > 120 milliseconds), the JTc interval may be used in place of the QTc with 
medical monitor approval.  The JTc must be < 340 milliseconds if JTc is used in place of 
the QTc.  Subjects with left bundle branch block are excluded. 
Note:  QTc prolongation due to pacemaker may enroll if the JTc is normal or with 
medical monitor approval. 
14. Evidence of HBV or HCV infection or risk of reactivation.  Subjects positive for HBV 
DNA, HCV RNA, HBsAg, or anti-HBc antibody may be included on a case by case basis 
with approval from medical monitor. 
Note:  Subjects with no prior history of hepatitis B infection who have been vaccinated 
against hepatitis B and who have a positive antibody against HBsAg test as the only 
evidence of prior exposure may participate in the study. 
15. Known history of drug-induced liver injury; alcoholic liver disease; nonalcoholic 
steatohepatitis; primary biliary cirrhosis; or ongoing extrahepatic obstruction caused by 
stones, cirrhosis of the liver, or portal hypertension. 
16. Known history of HIV; HIV 1/2 antibodies. 
17. Known allergy or reaction to any component of nivolumab, ipilimumab, or study drug or 
formulation components. 
18. Inability or unlikeliness to comply with the dose schedule and study evaluations, in the 
opinion of the investigator. 
19. Women who are pregnant or breastfeeding. 
20. Any condition that would, in the investigator's judgment, interfere with full participation 
in the study, including administration of study drug and attending required study visits; 
pose a significant risk to the subject; or interfere with interpretation of study data. 


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4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design 
This is an open-label, nonrandomized, Phase 1/2 study to determine the safety, tolerability, and 
efficacy of INCAGN01876 when given in combination with immune therapies.  Phase 1 will 
consist of a 3 + 3 + 3 dose escalation to determine the MTD, or PAD, defined as a dose that 
provides a maximal biochemical effect or an increase in biomarkers of immune activity of 
INCAGN01876 when given in combination with immune therapies.  Subjects with advanced or 
metastatic cervical cancer, endometrial cancer, gastric cancer (including stomach, esophageal, 
and GEJ), HCC, melanoma, Merkel cell carcinoma, mesothelioma, MSI-H CRC, NSCLC, 
ovarian cancer, SCCHN, SCLC, RCC, TNBC, and urothelial carcinoma who have progressed 
after treatment with available therapies that are known to confer clinical benefit, or who are 
intolerant to treatment, or who refuse standard of care will be enrolled in Phase 1.  The Phase 2 
expansion will further evaluate the safety, tolerability, and efficacy of the recommended dose(s) 
of INCAGN01876 selected in Phase 1 when given in combination with immune therapies.  
Subjects with advanced or metastatic cervical cancer, gastric cancer (including stomach, 
esophageal, and GEJ), SCCHN, PD-1 refractory SCCHN, and PD-1 or PD-L1 relapsed 
melanoma will be enrolled in Phase 2. 
The sponsor may elect to prioritize (or deprioritize) enrollment to specific treatment groups or 
cohorts based on emerging safety or efficacy data in collaboration with investigational sites.  
Additionally, alternate dose administration schedules and/or fixed doses of INCAGN01876 
(comparable to or less than the highest dose levels determined to be safe or pharmacologically 
active) may also be explored depending on 
 safety results. 
See Figure 1 for overall study design. 


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Figure 1: 
Overall Study Design 
 
4.1.1. 
Phase 1 – Dose Escalation 
A minimum of 3 evaluable subjects will be enrolled in each treatment group beginning with 
INCAGN01876 Dose Cohort 1 (0.1 mg/kg; starting dose).  A higher starting dose of 
INCAGN01876 may be used if safety data are available from the monotherapy study 
(INCAGN 1876-101) but will not exceed 1 dose level below the highest tolerated dose of 
INCAGN01876 monotherapy.  If a higher starting dose is used, the dose will be communicated 
to investigational sites with an administrative letter. 
The first 3 evaluable subjects enrolled within an INCAGN01876 dose cohort will be observed 
for the specified DLT observation period before the next dose cohort begins enrollment.  If 
0 DLTs occur in a cohort of 3 evaluable subjects, a new cohort of 3 evaluable subjects will be 
treated at the next higher dose level.  If 1 of 3 evaluable subjects experience a DLT, that cohort 
will be expanded to 6 evaluable subjects.  If 1 of 6 evaluable subjects experiences a DLT, a new 
cohort of 3 evaluable subjects will be treated at the next higher dose level.  If 2 of 6 evaluable 
subjects experience a DLT, that cohort will be expanded to 9 evaluable subjects.  If ≥ 2 of 3, 3 of 
6, or 3 of 9 evaluable subjects experience DLTs within a cohort, then that dose level will be 
determined to have exceeded the MTD, and the previous dose level will be considered the MTD.  
If only 3 evaluable subjects were treated at the MTD or PAD, then a minimum of 3 additional 
evaluable subjects will be enrolled before this dose is administered in Phase 2 of the study. 




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4.1.1.1.1. Treatment Group A (INCAGN01876 + Nivolumab) 
Treatment Group A will treat subjects with INCAGN01876 at the assigned dose level 
administered IV Q2W in combination with 240 mg of nivolumab administered IV Q2W 
(see Figure 2).  There will be a waiting period of 48 hours between dose administration of 
the first subject and second subject of each dosing cohort.  The first 3 evaluable subjects 
enrolled within a cohort will be observed for 28 days before the next cohort begins enrollment.  
Dose escalation of INCAGN01876 will proceed as outlined in Table 2 until the MTD or PAD of 
INCAGN01876 in combination with nivolumab is determined.   
Figure 2: 
Dosing Figure for Treatment Group A (INCAGN01876 + Nivolumab) 
 
4.1.1.1.2. Treatment Group B (INCAGN01876 Sequenced Dosing + Nivolumab) 
Treatment Group B will treat subjects with INCAGN01876 at the assigned dose level 
administered IV Q2W for a total of 2 doses followed by 240 mg of nivolumab administered IV 
Q2W starting at Cycle 3 (see Figure 3).  Alternate dose administration schedules may also be 
explored depending on 
 safety results.  The first 3 evaluable 
subjects enrolled within a cohort will be observed for 28 days starting after the first dose of 
nivolumab has been administered before the next cohort begins enrollment.  Dose escalation of 
INCAGN01876 will proceed as outlined in Table 2 until the MTD or PAD of INCAGN01876 in 
combination with nivolumab sequenced dosing is determined. 
Figure 3: 
Dosing Figure for Treatment Group B (INCAGN01876 Sequenced Dosing + 
Nivolumab) 
 
4.1.1.1.3. Treatment Group C (INCAGN01876 + Ipilimumab) 
Treatment Group C will treat subjects with INCAGN01876 at the assigned dose level 
administered IV Q2W in combination with 1 mg/kg of ipilimumab administered IV Q6W (see 
Figure 4).  There will be a waiting period of 48 hours between dose administration of the 
first subject and second subject of each dosing cohort.  The first 3 evaluable subjects enrolled 
within a cohort will be observed for 28 days before the next cohort begins enrollment.  Dose 
escalation of INCAGN01876 will proceed as outlined in Table 2 until the MTD or PAD of 
INCAGN01876 in combination with ipilimumab is determined. 




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4.1.1.2.1. Treatment Group D (INCAGN01876 + Nivolumab + Ipilimumab) 
Treatment Group D will treat subjects with INCAGN01876 at the assigned dose level 
administered IV Q2W in combination with 3 mg/kg of nivolumab administered IV Q2W and 
1 mg/kg of ipilimumab administered IV Q6W (see Figure 5).  There will be a waiting period of 
48 hours between dose administration of the first subject and second subject of each dosing 
cohort.  The first 3 evaluable subjects enrolled within a cohort will be observed for 28 days 
before the next cohort begins enrollment.  Dose escalation of INCAGN01876 will proceed as 
outlined in Table 2 until the MTD or PAD of INCAGN01876 in combination with nivolumab 
and ipilimumab is determined; however, the dose of INCAGN01876 in the triplet combination 
will not exceed the lowest MTD of INCAGN01876 established in the applicable doublet 
combinations.  For example, if the MTD of INCAGN01876 in combination with nivolumab is 
5 mg/kg and the MTD of INCAGN01876 in combination with ipilimumab is 3 mg/kg, then the 
dose of INCAGN01876 would not exceed 3 mg/kg. 
Figure 5: 
Dosing Figure for Treatment Group D (INCAGN01876 + Nivolumab + 
Ipilimumab) 
 
4.1.1.2.2. Treatment Group E (INCAGN01876 Sequenced Followed by Concurrent Dosing 
+ Nivolumab + Ipilimumab) 
Treatment Group E will treat subjects with INCAGN01876 at the assigned dose level 
administered IV Q2W for 2 doses followed by INCAGN01876 at the assigned dose level Q2W 
in combination with 3 mg/kg of nivolumab administered IV Q2W, and 1 mg/kg of ipilimumab 
administered IV Q6W (see Figure 6).  Alternate dose administration schedules may also be 
explored depending on 
 safety results.  The first 3 evaluable 
subjects enrolled within a cohort will be observed for 28 days starting after the first dose of 
nivolumab and ipilimumab has been administered before the next cohort begins enrollment.  
Dose escalation of INCAGN01876 will proceed as outlined in Table 2 until the MTD or PAD of 
INCAGN01876 in combination with nivolumab and ipilimumab is determined; however, the 
dose of INCAGN01876 in the triplet combination will not exceed the lowest MTD of 
INCAGN01876 established in the applicable doublet combinations.  For example, if the MTD of 
INCAGN01876 in combination with nivolumab is 5 mg/kg and the MTD of INCAGN01876 in 
combination with ipilimumab is 3 mg/kg, then the dose of INCAGN01876 would not exceed 
3 mg/kg. 








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up to 24 months from the first dose of study treatment, whichever occurs first.  If the subject 
discontinues study treatment, the treatment period will end and the subject will enter the 
follow-up period (see Section 6.4).  Study participation, including post-treatment follow-up is 
expected to average approximately 12 to 18 months per individual subject. 
4.5. 
Overall Study Duration 
The study begins when the first subject signs the ICF.  The end of the study will occur when all 
subjects have discontinued treatment and the last follow-up visit has been performed. 
If there are ≤ 5 subjects on study for more than 6 months, a database lock of the study may occur 
to allow the analysis of the study data.  Any remaining subjects may continue to receive study 
treatment and be seen by the investigator per usual standard of care for this population.  The 
investigator will be expected to monitor for and report any AEs, SAEs, pregnancies, and deaths 
as detailed in Section 8 and Section 6.4.3.  The remaining subjects are considered to be on study 
until a discontinuation criterion is met and written notification is provided to the sponsor. 
4.6. 
Study Termination 
The investigator retains the right to terminate study participation at any time, according to the 
terms specified in the study contract.  The investigator is to notify the IRB/IEC in writing of the 
study's completion or early termination, send a copy of the notification to the sponsor or 
sponsor's designee, and retain 1 copy for the site study regulatory file. 
The sponsor may terminate the study electively, if required by regulatory decision, or upon 
review of emerging data.  If the study is terminated prematurely, the sponsor will notify the 
investigators, the IRBs and IECs, and regulatory bodies of the decision and reason for 
termination of the study. 


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5. 
TREATMENT 
5.1. 
Treatment Assignment 
5.1.1. 
Subject Numbering and Treatment Assignment 
Each subject will be identified in the study by a subject ID number, which is a combination of 
the site ID and subject number.  Site staff should contact the IRT to obtain the subject ID number 
and confirm a slot is available during prescreening.  This subject ID number will be maintained 
throughout the study and will not be reassigned.  Subjects who fail screening and are repeating 
the screening process due to a change in eligibility status will be assigned a new subject ID 
number.  The site staff will contact the IRT to enroll the subject and obtain the study drug and 
treatment group assignment.  All subsequent cycles will follow this process.  The IRT will also 
be contacted for ordering study drug supplies and when subjects are discontinued from treatment.  
Full details will be provided in the IRT manual. 
5.1.2. 
Randomization and Blinding 
This is an open-label nonrandomized study; therefore, randomization and blinding do not apply.   
5.2. 
Study Drugs 
5.2.1. 
INCAGN01876 
5.2.1.1. 
Description and Administration 
The study drug (INCAGN01876) is supplied as a sterile, single-use solution for injection, in a 
10 mL glass vial.  Each vial contains 50 mg of INCAGN01876 in 5 mL at a concentration of 
10 mg/mL in 
, and pH 
  The infusion site 
should not be used for blood sampling. 
Study drug will be diluted in 
 or acceptable admixture as outlined in the 
Pharmacy Manual and will be administered by qualified site personnel as an IV infusion over a 
30-minute (-5/+10 minutes) period on Day 1 of each cycle when INCAGN01876 is scheduled to 
be given.  On days when INCAGN01876 will be administered along with other agents 
administered by infusion, INCAGN01876 will be administered first, followed by a 30-minute 
wait before administration of the subsequent immune therapy/therapies. 
In Phase 1, subjects will be administered study drug, according to cohort enrollment (see 
Table 2), Q2W (14-day cycles), in combination with immune therapies.  In Phase 2, subjects will 
be administered study drug at the recommended dose Q2W (14-day cycles), in combination with 
immune therapies.  In Treatment Group B, INCAGN01876 is only administered on Day 1 of 
Cycles 1 and 2. 
Subjects will continue to receive INCAGN01876 as long as they are deriving benefit and have 
not met any of the Protocol-defined conditions for treatment withdrawal (see Section 5.5), or for 
up to 24 months from the first dose of study treatment, whichever occurs first. 


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5.2.1.2. 
Supply, Packaging, and Labeling 
Study drug will be supplied as a sterile, single-use solution for injection in 10 mL glass vials.  
Study drug will be packaged as open-labelled supplies; each vial will be labelled and placed in a 
carton.  The Pharmacy Manual contains additional information regarding supply, packaging, and 
labeling of study drug. 
The investigator shall take responsibility for and shall take all steps to maintain appropriate 
records and ensure appropriate supply, storage, handling, distribution, and usage of study drug in 
accordance with the Protocol and any applicable laws and regulations. 
All Incyte investigational product labels will be in the local language and will comply with the 
legal requirements of each country. 
5.2.1.3. 
INCAGN01876 Storage 
Study drug must be stored refrigerated (2°C-8°C) and protected from light, in a secure, limited 
access location.  Receipt and dispensing of study drug must be recorded by an authorized person 
at the study site.  Study drug may not be used for any purpose other than that stated in the 
Protocol.  The Pharmacy Manual contains additional information regarding storage of study 
drug. 
5.2.2. 
Standard Immune Therapies 
5.2.2.1. 
Nivolumab 
Nivolumab will be administered IV per the package insert or institutional guidelines at the site, at a 
dose that is dependent on the assigned treatment group as follows: 
• Doublet Treatment Groups A, B, F, and H:  240 mg on Day 1 of every 2-week 
(ie, 14-day) cycle. 
• Triplet Treatment Groups D, E, J, and L:  3 mg/kg on Day 1 of every 2-week 
(ie, 14-day) cycle. 
• Concurrent dosing Treatment Groups A, D, F, and J:  Nivolumab dosing will begin 
on Cycle 1 Day 1. 
• Sequenced dosing Treatment Groups B, E, H, and L:  Nivolumab dosing will begin 
on Cycle 3 Day 1. 
Nivolumab will be administered at least 30 minutes after the infusion of INCAGN01876 (when 
applicable), and subjects will continue to receive nivolumab as long as the subject is deriving 
benefit and has not met any of the Protocol-defined conditions for treatment withdrawal (see 
Section 5.5), or for up to 24 months from the first dose of study treatment, whichever occurs 
first. 


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Nivolumab is commercially available.  Investigators are responsible for ensuring that subjects 
receive commercially available supplies of nivolumab for the entire duration of study 
participation.  Incyte may provide certain standard of care medications such as nivolumab where 
required by applicable law or specific regulation or under other circumstances when subjects 
may not otherwise have access to them.  Nivolumab must be used in accordance with the storage 
conditions and shelf life in the manufacturer's approved label. 
5.2.2.2. 
Ipilimumab 
Ipilimumab will be administered IV per the package insert or institutional guidelines at the site, at 
a dose that is dependent on the assigned treatment group as follows: 
• Doublet Treatment Group C and C2 (Phase 2 Expansion) and Triplet Treatment 
Groups D, E, J, and L:  1 mg/kg on Day 1 of every 6-week (eg, 42-day) cycle. 
• Concurrent dosing Treatment Groups C and C2 (Phase 2 Expansion), D, and J:  
Ipilimumab dosing will begin on Cycle 1 Day 1. 
• Sequenced dosing Treatment Groups E and L:  Ipilimumab dosing will begin on 
Cycle 3 Day 1.   
Ipilimumab will be administered at least 30 minutes after the infusion of INCAGN01876 (when 
administered on the same day).  Ipilimumab will always be administered after INCAGN0876 and 
nivolumab.  Subjects will continue to receive ipilimumab as long as the subject is deriving 
benefit and has not met any of the Protocol-defined conditions for treatment withdrawal (see 
Section 5.5), or for up to 24 months from the first dose of study treatment, whichever occurs 
first. 
At the sponsor's discretion, once the MTD or PAD of INCAGN01876 has been established with 
ipilimumab at 1 mg/kg Q6W, a higher dose of ipilimumab at 3 mg/kg Q6W and/or 3 mg/kg 
Q3W for 4 doses may be tested. 
Ipilimumab is commercially available.  Investigators are responsible for ensuring that subjects 
receive commercially available supplies of ipilimumab for the entire duration of study 
participation.  Incyte may provide certain standard of care medications such as ipilimumab where 
required by applicable law or specific regulation or under other circumstances when subjects 
may not otherwise have access to them.  Ipilimumab must be used in accordance with the storage 
conditions and shelf life in the manufacturer's approved label.  
5.3. 
Treatment Compliance  
5.3.1. 
Treatment Compliance of INCAGN01876, Nivolumab, and Ipilimumab 
INCAGN01876, nivolumab, and ipilimumab are administered as an IV infusion by site 
personnel.  Receipt of infusions will be documented by the site staff and monitored by the 
sponsor/designee. 






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5.4.3. 
Management of Dose-Limiting Toxicities or Other Urgent Situations 
In all cases, investigators may employ any measures or concomitant medications, after 
discussion with the medical monitor (whenever possible), necessary to optimally treat the 
subject. 
5.4.4. 
Follow-Up of Dose-Limiting Toxicities 
Any DLT should be followed until it resolves to baseline or appears to have stabilized for a 
minimum of 4 weeks (eg, 28 days).  During follow-up, subjects should be seen as often as 
medically indicated to assure safety. 
5.4.5. 
Procedures for Cohort Review and Dose Escalation 
Telephone conferences will be scheduled by the sponsor with study investigators in order to 
review cohort-specific data and overall safety data, to agree on dose escalation, adjudicate 
individual high-grade AEs as potentially dose-limiting, and guide other major study decisions. 
5.4.6. 
Criteria and Procedures for Dose Interruptions of Study Drug 
Treatment with INCAGN01876 in combination with standard immune therapies may be delayed 
up to 4 weeks (28 days) to allow for resolution of toxicity.  If an interruption or 
discontinuation is necessary, all study treatments should be interrupted or discontinued.  
Subjects may resume treatment if no medical condition or other circumstance exists that, in the 
opinion of the investigator, would make the subject unsuitable for further participation in the 
study.  The treating investigator should contact the medical monitor to discuss the case of any 
subject whose treatment has been delayed for more than 4 weeks (28 days) before restarting 
treatment. 
Instructions for INCAGN01876 dose interruptions are outlined in Table 7.  Individual decisions 
regarding dose interruptions of study drug should be made using clinical judgment and in 
consultation with the medical monitor (whenever possible), taking into account relatedness of the 
AE to the study drug and the subject's underlying condition.  Adverse events that have a clear 
alternative explanation, or transient (≤ 72 hours) abnormal laboratory values without associated 
clinically significant signs or symptoms, may be exempt from dose-interruption rules.  
Dose interruptions are permitted in the case of medical/surgical events or logistical reasons not 
related to study therapy (eg, elective surgery, unrelated medical events, subject vacation, and/or 
holidays).  Subjects should be placed back on study therapy within 4 weeks (28 days) of the 
scheduled interruption, unless otherwise discussed with the medical monitor.  The reason for 
interruption should be documented in the subject's study record. 


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Table 7: 
Criteria for Interruption and Restarting of Study Treatment 
CTCAE  
Grade/Severity 
Hold 
Treatment 
(Y/N) 
Timing for  
Restarting 
Treatment 
Dose Level for 
Restarting  
INCAGN01876 
Dose Level for 
Restarting 
Immune 
Therapies 
Treatment 
Discontinuation 
1-2 
(Mild-Moderate) 
No 
Continue treatment 
at the discretion of 
the investigator. 
N/A 
NA 
N/A 
3 
(Severe) 
Yes 
Toxicity resolves to 
Grade 0-1. 
Restart same dose  
Restart same dose 
Toxicity does not 
resolve within 
4 weeks (28 days) 
of last dose, except 
by approval of the 
medical monitor. 
OR 
Second occurrence 
of previously 
resolved Grade 3 
AE. 
4 
(Life-threatening) 
Yes 
Permanent 
discontinuation, 
except by approval 
of the medical 
monitor. 
If continuing, 
toxicity must resolve 
to Grade 0-1. 
Permanent 
discontinuation, 
except by approval 
of the medical 
monitor. 
If continuing, restart 
same dose.  
Permanent 
discontinuation, 
except by 
approval of the 
medical monitor. 
If continuing, 
restart same dose. 
Permanent 
discontinuation for 
any severe or 
life-threatening 
event, except by 
approval of the 
medical monitor. 
5.4.7. 
Management of Immune-Related Adverse Events 
INCAGN01876, nivolumab, and ipilimumab are considered immune modulators, and it is 
possible that irAEs (both nonserious and serious) may occur.  Adverse events of a potential 
immunologic etiology or irAEs may be defined as an AE consistent with an immune 
phenomenon associated with drug exposure after all other etiologies have been eliminated.  
Immune-related AEs may be expected based on the nature of the study treatment, their 
mechanism of action, and reported experience with these and other immunotherapies.  Special 
attention should be paid to AEs that may be suggestive of potential irAEs.  An irAE can occur 
shortly after the first dose or several months after the last dose of treatment.  Suspected irAEs 
should be discussed with the medical monitor when possible. 
Subjects should receive appropriate supportive care measures as deemed necessary by the 
treating investigator.  Suggested supportive care measures for the management of drug-related 
AEs with potential immunologic etiology are outlined in Table 8.  Detailed supportive care 
guidelines for specific irAEs can be in found in Appendix B.  Nivolumab and ipilimumab are 
approved therapies and have specific irAE management guidelines within their package insert; 
the treating investigator may use labeled guidance or institutional guidelines for the management 
of irAEs if preferred.  For each AE, attempts should be made to rule out other causes, including 
but not limited to metastatic disease or bacterial or viral infection, which might require specific 
supportive care.   


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Table 8: 
Supportive Care Guidelines for Immune-Related Adverse Events 
CTCAE Grade/Severity 
Supportive Carea 
Grade 1 (mild) 
• Monitor symptoms and provide symptomatic treatment. 
Grade 2 (moderate) 
• Monitor symptoms and provide symptomatic treatment. 
• Consider consultation with specialists as necessary. 
• Consider systemic corticosteroids per institutional standard of care. 
Grade 3-4  
(severe–life-threatening) 
• Monitor symptoms and provide symptomatic treatment. 
• Consider consultation with specialists as necessary. 
• Administer corticosteroids per institutional standard of care. 
• More potent immunosuppressive therapies should be considered for events not 
responding to systemic steroids after discussing with the medical monitor. 
• Study treatment may be permanently discontinued for clinically significant or 
severe irAEs, or for events where steroid course cannot be tapered below 
7.5 mg/day prednisone or equivalent to manage symptoms. 
a Detailed supportive care guidelines for specific irAEs can be found in Appendix B. 
5.4.8. 
Management of Infusion Reactions 
Table 9 shows treatment guidelines for subjects who experience an infusion reaction associated 
with administration of study treatment.  Signs and symptoms usually develop during or shortly 
after drug infusion and generally resolve completely within 24 hours of completion of infusion.  
Nivolumab and ipilimumab are approved therapies and may have specific infusion reaction 
management guidelines within their package insert; the treating investigator may use labeled 
guidance or institutional guidelines for the management of infusion reactions if preferred. 


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Table 9: 
Infusion Reaction Treatment Guidelines 
CTCAE Grade 
Treatment 
Premedication at  
Subsequent Dose 
Administration 
Grade 1: 
Mild reaction; infusion 
interruption not indicated; 
intervention not indicated. 
Increase monitoring of vital signs as 
medically indicated until the subject is 
deemed medically stable in the opinion of the 
investigator. 
None. 
Grade 2: 
Requires infusion interruption 
but responds promptly to 
symptomatic treatment  
(eg, antihistamines, NSAIDs, 
narcotics, IV fluids); 
prophylactic medications 
indicated for ≤ 24 hours. 
Stop infusion and monitor symptoms. 
Additional appropriate medical therapy may 
include but is not limited to the following: 
• IV fluids 
• Antihistamines 
• NSAIDs 
• Acetaminophen 
• Narcotics 
Increase monitoring of vital signs as 
medically indicated until the subject is 
deemed medically stable in the opinion of the 
investigator. 
If symptoms resolve within 1 hour of stopping 
drug infusion, the infusion may be restarted at 
50% of the original infusion rate.  Otherwise, 
dose administration will be held until 
symptoms resolve, and the subject should be 
premedicated for the next scheduled dose. 
Subjects who develop Grade 2 toxicity despite 
adequate premedication should be 
permanently discontinued from further study 
treatment. 
Subject may be premedicated 1.5 
h (± 30 min) before infusion with 
the following: 
• Diphenhydramine 50 mg orally 
(or equivalent dose of 
antihistamine). 
• Acetaminophen 500-1000 mg 
orally (or equivalent dose of 
antipyretic). 
Grade 3: 
Prolonged (ie, not rapidly 
responsive to symptomatic 
medication and/or brief 
interruption of infusion); 
recurrence of symptoms 
following initial 
improvement; hospitalization 
indicated for other clinical 
sequelae (eg, renal 
impairment, pulmonary 
infiltrates). 
Stop infusion. 
Additional appropriate medical therapy may 
include but is not limited to the following: 
• IV fluids 
• Antihistamines 
• NSAIDs 
• Acetaminophen 
• Narcotics 
• Oxygen 
• Pressors 
• Corticosteroids 
• Epinephrine 
Increase monitoring of vital signs as 
medically indicated until the subject is 
deemed medically stable in the opinion of the 
investigator. 
Hospitalization may be indicated. 
Subject is permanently discontinued from 
further study treatment. 
No subsequent dose. 
Grade 4: 
Life-threatening; pressor or 
ventilatory support indicated. 
Note:  Appropriate resuscitation equipment should be available in the room and a physician readily available during the period of 
drug administration. 


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5.4.9. 
Criteria for Permanent Discontinuation of Study Drug 
The occurrence of unacceptable toxicity not caused by the underlying malignancy will be 
presumed to be related to study treatment and will require that the study treatment be 
permanently discontinued.  Unacceptable toxicity is defined as follows: 
• Grade 4 or life-threatening AEs, except with approval from the medical monitor. 
• ≥ Grade 2 ocular irAE. 
• Occurrence of an AE that is related to treatment, in the judgment of the investigator 
or the medical monitor, and compromises the subject's ability to continue 
study-specific procedures or is considered to not be in the subject's best interest. 
• Persistent AE requiring a delay of treatment for more than 4 weeks (28 days) unless a 
greater delay has been approved by the sponsor. 
5.5. 
Withdrawal of Subjects From Study Treatment 
5.5.1. 
Withdrawal Criteria 
A subject may choose to withdraw from the study treatment at any time or be withdrawn from 
the study treatment by the investigator or sponsor, if the subject is noncompliant with the study 
requirements.  If permanent discontinuation of any of the study treatments is necessary 
(eg, INCAGN01876, nivolumab, ipilimumab), all study treatments, will be discontinued.  If a 
subject is withdrawn from study treatment, then every reasonable effort should be made to 
determine the reason for withdrawal, and this information should be recorded in the eCRF. 
Subjects must be withdrawn from study treatment for the following reasons: 
• The subject becomes pregnant. 
• Consent is withdrawn.  Subjects may choose to withdraw from the study at any time 
without penalty of jeopardizing their health care or loss of benefits to which the 
subject is otherwise entitled. 
Note:  Consent withdrawn means that the subject can no longer be followed and no 
additional data can be collected.  Subjects may choose to discontinue study treatment 
and remain in the study to be followed for progression and survival.  
Note:  As of Protocol Amendment 5, subjects who withdraw consent will no longer 
be followed for progression and survival beyond the last safety follow-up visit.  
• Further participation would be injurious to the subject's health or well-being, in the 
investigator's medical judgment. 
• Unacceptable toxicity (see Section 5.4.9).  Subjects with unacceptable toxicities must 
be withdrawn from study treatment but will continue in the follow-up phase of the 
study (see Section 6.4). 
• The study is terminated by the sponsor. 
• The study is terminated by the local health authority, IRB, or IEC. 


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A subject may be discontinued from study treatment as follows: 
• Confirmed radiographic progression of disease per RECIST v1.1 (see Section 7.7.1).  
A subject may be granted an exception to continue on treatment with confirmed 
radiographic progression if clinically stable or clinically improved (see Section 7.7.1). 
Note:  For unconfirmed progression see Section 7.7.1. 
• If, during the course of the study, a subject is found not to have met eligibility criteria 
(see Section 3), the medical monitor, in collaboration with the investigator, will 
determine whether the subject should be withdrawn from the study. 
• If a subject is lost-to-follow-up or noncompliant with study procedures or study 
treatment in the investigator's opinion, the sponsor should be consulted for instruction 
on handling the subject. 
5.5.2. 
Withdrawal Procedures 
In the event that the decision is made to permanently discontinue the study treatment, the subject 
will be withdrawn, and the EOT visit should be conducted.  Reasonable efforts should be made 
to have the subject return for all applicable follow-up visits (safety and efficacy; see Section 6.4).  
The last date of the last dose of study treatment and the reason for subject withdrawal will be 
recorded in the eCRF. 
If a subject is withdrawn from the study treatment: 
• The study monitor or sponsor must be notified. 
• The reason(s) for withdrawal from treatment must be documented in the subject's 
medical record and in the eCRF.   
Note:  The reason for withdrawal from treatment may be different than the reason for 
withdrawal from study.  For example, subjects can discontinue treatment for disease 
progression or toxicity, but remain in the study for safety and survival follow-up.   
Note:  As of Protocol Amendment 5, subjects who discontinue treatment will no 
longer be followed for progression and survival beyond the last safety follow-up visit. 
• The EOT visit should be performed. 
• The date of the EOT visit should be recorded in the eCRF and IRT. 
• Subjects must be followed for safety until the time of the follow-up visit or until 
study treatment–related toxicities resolve, return to baseline, or are deemed 
irreversible, or until the subject begins new anticancer therapy, whichever is longest. 
• Subjects who discontinue for reasons other than disease progression will continue to 
be followed for disease status as outlined in Section 6.4.2. 
Note:  As of Protocol Amendment 5, subjects who discontinue for reasons other than 
disease progression will no longer be followed for disease status beyond the last 
safety follow-up visit. 


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• All subjects who discontinue study treatment will continue to be followed for OS as 
outlined in Section 6.4.3. 
Note:  As of Protocol Amendment 5, subjects who discontinue study treatment will 
no longer be followed for survival beyond the last safety follow-up visit. 
If the subject discontinues study treatment and actively withdraws consent for collection of 
follow-up data (safety follow-up, disease assessments, or survival follow-up), then no additional 
data collection should occur; however, subjects will have the option of withdrawing consent 
for study treatment but continuing in the follow-up period of the study for safety, efficacy, 
and survival assessments. 
Note:  As of Protocol Amendment 5, subjects who withdraw consent but continue in the 
follow-up period will be followed for efficacy and survival until the last safety follow-up visit. 
5.6. 
Concomitant Medications 
All concomitant medications and treatments must be recorded in the eCRF.  Any prior 
medication received up to 28 days before the first dose of study treatment and 60 days after the 
last dose of study treatment, or until the subject begins a new anticancer therapy, whichever 
occurs first, will be recorded in the eCRF.  Any addition, deletion, or change in the dose of these 
medications will also be recorded.  Concomitant treatments/procedures that are required to 
manage a subject's medical condition during the study will also be recorded in the eCRF. 
5.6.1. 
Permitted Medications 
All treatments that the investigator considers necessary for a subject's welfare may be 
administered at the discretion of the investigator in keeping with the community standards of 
medical care.  All concomitant medications will be recorded on the eCRF, including all 
prescription, over-the-counter, herbal supplements, and IV medications and fluids.  If changes 
occur during the study period, documentation of drug regimen, frequency, route, and date may 
also be included on the eCRF.  Note:  The use of bisphosphonates and denosumab are permitted 
in this study. 
5.6.2. 
Restricted Medications 
Systemic glucocorticoids for any purpose other than prophylaxis for contrast allergies for 
radiographic procedures, or to modulate symptoms or treat an AE of suspected immunologic 
etiology, are restricted and require medical monitor approval.  The use of physiologic 
corticosteroid replacement therapy may be approved after consultation with the medical monitor. 
Note:  Inhaled and topical steroids are allowed.  A short course of steroids (prednisone or 
equivalent) ≤ 10 mg/day may be permitted with medical monitor approval. 
5.6.3. 
Prohibited Medications 
Medications or vaccinations specifically prohibited in the exclusion criteria (see Section 3.2) are 
not allowed during the study.  If there is a clinical indication for one of these medications or 
vaccinations specifically prohibited during the study, discontinuation from study treatment may 
be required.  The investigator should discuss any questions regarding this with the medical 
monitor.  The final decision on any supportive therapy or vaccination rests with the investigator 


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and/or the subject's primary physician.  However, the decision to continue the subject on study 
treatment requires the mutual agreement of the investigator, the sponsor, and the subject. 
Subjects are prohibited from receiving the following therapies during the screening and treatment 
periods of this study, unless otherwise indicated: 
• Any anticancer medications, including chemotherapy or biologic therapy other than study 
treatment. 
• Any immunological-based treatment for any reason from screening through the safety 
follow-up visit is prohibited. 
Note:  Completed adjuvant therapy (eg, vaccines) with medical monitor approval, inhaled 
or topical steroids, systemic steroids at doses ≤ 10 mg/day prednisone or equivalents, and 
immune suppressants are allowed for treatment for immune toxicities as described in 
Section 5.4.7 and Appendix B, or as prophylaxis for contrast allergy for imaging 
procedures. 
Note:  Allergy shots may be permitted after consultation with the medical monitor. 
• Investigational agents other than study treatment.  Use of such medications from 
screening through the safety follow-up visit is prohibited. 
• Concomitant radiation therapy. 
Note:  Radiation therapy to a symptomatic solitary lesion or to the brain may be 
considered on an exceptional case-by-case basis after consultation with the medical 
monitor.  The subject must have clear measurable disease outside the radiated field.  
Administration of palliative radiation therapy will be considered clinical progression for 
the purposes of determining PFS. 
• Live vaccines within 30 days before the first dose of study treatment and while 
participating in the study.  Examples of live vaccines include, but are not limited to, the 
following:  measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus 
Calmette–Guérin, and typhoid (oral) vaccine.  Seasonal influenza vaccines for injection 
are generally killed virus vaccines and are allowed.  However, intranasal influenza 
vaccines are live attenuated vaccines and are not allowed. 
Subjects who, in the assessment by the investigator, require the use of any of the aforementioned 
treatments for clinical management should be removed from the study.  Subjects may receive 
other medications that the investigator deems to be medically necessary.  The exclusion criteria 
describe other medications that are prohibited in this study.  There are no prohibited therapies 
during the post-treatment follow-up period. 


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6. 
STUDY ASSESSMENTS 
All study assessments will be performed as indicated in the schedule of clinical assessments 
(Table 10), and all laboratory assessments will be performed as indicated in Table 11.  Table 12 
presents a summary of clinical laboratory analytes to be assessed.  The order of assessments is 
suggested by the order of mention within the schedule.  See Section 7 for instructions on each 
assessment.  Further details of study procedures and assessments can be found in the study 
reference manual or applicable procedural documentation. 


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Table 10: 
Schedule of Clinical Assessments 
Visit Day (Range) 
Protocol 
Section 
Screening 
Treatmenta 
Post-Treatmentb 
Cycles 1 and 6 
All Other 
Cycles 
Every 
8 weeks 
EOT 
Safety 
Follow-Up 
Visit 1c 
Safety 
Follow-Up 
Visit 2c 
Survival 
Follow-Upd 
Day 1 
Day 8 
Day 1 
Disease 
Status 
Evaluation/Window 
Day -28 
to -1 
± 3 
dayse 
± 1 
day 
± 3 days 
± 7 days 
± 3 days 
30 days 
(+ 7 days) 
60 days 
(+ 7 days) 
Every 
12 weeks        
(± 7 days) 
Administrative procedures 
Informed consent 
7.1 
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
3.1, 3.2 
X 
X 
 
 
 
 
 
 
 
Contact IRT 
7.2 
X 
X 
 
X 
 
X 
 
 
 
Medical and cancer history 
7.3.1  
7.3.2 
X 
 
 
 
 
 
 
 
 
Prior/concomitant 
medications 
7.4 
X 
X 
X 
X 
 
X 
X 
X 
 
Administer INCAGN01876 
5.2.1.1 
 
Xf 
 
Xf 
 
 
 
 
 
Administer nivolumab 
5.2.2.1 
 
Xg 
 
Xg 
 
 
 
 
 
Administer ipilimumab 
5.2.2.2 
 
Xh 
 
Xh 
 
 
 
 
 
Poststudy anticancer therapy 
status 
7.5 
 
 
 
 
 
 
X 
X 
 
Survival status 
6.4.3 
 
 
 
 
 
 
 
 
X 
Clinical procedures/assessments 
 
Comprehensive physical 
examination 
(including height ) 
7.6.2.1 
X 
 
 
 
 
 
 
 
 
Targeted physical 
assessment 
7.6.2.2 
 
X 
Xi 
X 
 
X 
X 
X 
 
Vital signs and weight  
7.6.3 
X 
X 
Xi 
X 
 
X 
X 
X 
 
ECOG performance status 
7.8.1 
X 
X 
Xi 
X 
 
X 
X 
X 
 
Laboratory assessments 
7.6.5 
X 
X 
X 
X 
 
X 
X 
X 
 
12-lead ECGj 
7.6.4 
X 
 
 
 
X 
X 
X 
 
 
AE assessment 
7.6.1 
X 
X 
Xi 
X 
 
X 
X 
X 
 
Efficacy measurements 
Radiologic tumor 
assessments 
7.7 
Xk 
 
 
 
Xl 
Xm 
Xn 
 
a Treatment cycles will be Q2W (14 days ± 3 days).  Alternate dose administration schedules and/or fixed doses of INCAGN01876 (comparable to or less than the highest dose 
levels determined to be safe or pharmacologically active), may also be explored depending on 
 safety results. 
b The mandatory safety follow-up visits should be conducted approximately 30 days and 60 days after the last dose of study treatment or before the initiation of a new anticancer 
treatment, whichever comes first. 
c As of Protocol Amendment 5, the safety follow-up visits will include AE and concomitant medication assessment only and may be completed remotely (such as by televisit). 


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d As of Protocol Amendment 5, no further survival follow-up assessment will be required beyond the last safety follow-up visit. 
e Evaluation window only applies to Cycle 6 Day 1. 
f In Treatment Group B, INCAGN01876 is only administered on Day 1 of Cycles 1 and 2. 
g In Treatment Groups B, E, H, and L, nivolumab administration begins at Cycle 3 Day 1. 
h For subjects enrolled into Treatment Groups C and C2 (INCAGN01876 + ipilimumab) and Treatment Groups D and J (INCAGN01876 + nivolumab + ipilimumab), ipilimumab 
will be administered on Cycle 1 Day 1 and then  Day 1 of every 3rd cycle (Cycle 1, Cycle 4, Cycle 7, etc).  In Treatment Groups E and L ipilimumab administration begins at 
Cycle 3 Day 1 and then continues on Day 1 of every third cycle.  If higher doses of ipilimumab are tested (eg, 3 mg/kg every 3 weeks [21 days] for 4 doses), then ipilimumab 
will be administered on Day 1 of each 3-week (21-day) cycle for a total of 4 doses.  If the scheduled ipilimumab doses fall on days other than Day 1 of a cycle, the subjects will 
need to be present in clinic for the infusion, and any standard procedures required by the site should be performed. 
i Applicable to all subjects at Cycle 1 Day 8.  At Cycle 6 Day 8, only required if subject is experiencing AEs > Grade 2. 
j All 12-lead ECGs will be performed with the subject in a recumbent or semirecumbent position after 5 minutes of rest and should not be performed within 15 minutes after a 
blood collection.  ECGs will be collected at screening and at least every 8 weeks, or as clinically indicated per prescribing instructions for nivolumab, as well as the EOT and 
first safety follow-up visits. 
k The initial tumor imaging will be performed within 28 days before the first dose of study treatment.  Images of the chest, abdomen, and pelvis are required for all subjects.  Scans 
performed as part of routine clinical management are acceptable for use as the screening scan if they are of diagnostic quality and performed within 28 days before the first dose 
of study treatment.  The same imaging technique should be used for a subject throughout the study.  Local reading (investigator assessment with site radiology reading) will be 
used to determine eligibility and for subject management. 
l On-study imaging will be performed at Week 8 and then every 8 weeks (± 7 days) for the first 12 months and then every 12 weeks (± 7 days) thereafter.  Imaging should follow 
calendar days starting with Day 1 of INCAGN01876 treatment and should NOT be adjusted for delays in cycle starts.  If imaging shows disease progression, then another 
imaging assessment should be performed at a minimum of 4 weeks but no later than 6 weeks later to confirm progression per mRECIST. 
m If scan was obtained within 4 weeks before the date of discontinuation, then a scan at treatment discontinuation (EOT) is not mandatory.  For subjects who discontinue study 
therapy without confirmed disease progression, a radiologic evaluation should be repeated at the time of treatment discontinuation (ie, date of discontinuation ± 4 week window). 
n For subjects who discontinue treatment for reasons other than disease progression, every effort should be made to continue monitoring their disease status every 8 weeks 
(± 7 days) by radiographic imaging until 1) start of new anticancer therapy, 2) documented disease progression, 3) death, 4) the end of the study, or 5) withdrawal of consent, 
whichever occurs first. 
Note:  As of Protocol Amendment 5, no further disease status follow-up assessments will be required beyond the last safety follow-up visit. 


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Table 11: 
Schedule of Laboratory Assessments 
Visit Day (Range) 
Protocol 
Section 
Timing of 
Assess-
ment 
Screening 
Treatment 
Post-Treatment 
C1 
C2 
C3 
C4 
C6 
C7 
Every 4th 
Cycle  
(C8, C12) 
All 
Other 
Cycles 
EOT 
Safety 
Follow-Up 
Visit 1 
Safety 
Follow-Up 
Visit 2 
D1 
D8 
D1 
D1 
D1 
D1 
D8 
D1 
D1 
D1 
Evaluation/Window 
Day -28 
to -1 
 
± 1 
day 
± 3 
days 
± 3 
days 
± 3 
days 
± 3 
days 
± 3 
days 
± 3 
days 
± 3 days 
± 3 
days 
± 3 
days 
30 days  
(+ 7 days) 
60 days  
(+ 7 days) 
Local laboratory testsa 
Comprehensive serum 
chemistriesb 
7.6.5 
N/A 
Xc 
Xd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology with 
differential 
7.6.5 
N/A 
Xc 
Xd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation panele 
7.6.5 
N/A 
Xc 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urinalysis 
7.6.5 
N/A 
Xc 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Endocrine function tests 
7.6.5 
N/A 
Xc 
 
 
 
 
X 
 
 
 
X 
 
X 
X 
 
Hepatitis B and C 
7.6.5.2 
N/A 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy test 
(childbearing females 
only)f 
7.6.5.1 
N/A 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Urine pregnancy test 
(childbearing females 
only) 
7.6.5.1 
N/A 
 
Xg 
 
 
 




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Table 12: 
Local Laboratory Tests:  Required Analytes 
Serum Chemistries 
Hematology 
Urinalysis 
Hepatitis 
Screeninga 
Coagulation 
Albumin 
Alkaline phosphatase 
ALT 
AST  
Bicarbonate or CO2 
Blood urea nitrogen or 
urea 
Calcium 
Chloride  
Creatinine 
Glucose 
Lactate dehydrogenase 
Phosphate 
Potassium 
Sodium 
Total bilirubin 
Direct bilirubin (if total 
bilirubin is elevated 
above ULN) 
Total protein 
Uric acid 
Amylase 
Lipase 
Complete blood 
count, including: 
• Hemoglobin 
• Hematocrit 
• Platelet count 
• Red blood cell 
count 
• White blood cell 
count 
 
Absolute values 
must be provided 
for WBC 
differential 
laboratory results: 
• Basophils 
• Eosinophils 
• Lymphocytes 
• Monocytes 
• Neutrophils 
Color and 
appearance 
pH and specific 
gravity 
Bilirubin 
Glucose 
Ketones 
Leukocytes 
Nitrite 
Occult blood 
Protein 
HBsAg 
anti-HBc antibody 
HBV-DNA 
HCV antibody 
HCV-RNA 
PT 
aPTT 
INR 
Pregnancy 
Testing 
Endocrine 
Monitoring 
Female subjects of 
childbearing 
potential only 
require a serum 
test at screening 
and EOT. 
Pregnancy tests 
(serum or urine) 
should be repeated 
if required by local 
regulations. 
Thyroid-stimulating 
hormone (TSH) 
Free thyroxine (T4) 
Total triiodothyronine 
(T3)/FT3b 
a No HCV-RNA test is required in case HCV antibody test result is negative.  No HBV DNA test is required in case HBsAg and 
anti-HBc antibody testing are negative. 
b If considered standard by your region. 
6.1. 
Screening 
Screening is the interval between signing the ICF and the day the subject is enrolled in the study 
(eg, Cycle 1 Day 1).  Screening may not exceed 28 days.  Informed consent must be obtained 
before performing any study-specific procedures that are not considered standard of care; 
however, procedures conducted as part of the subject's routine clinical management obtained 
before signing of informed consent may be used for screening or baseline purposes with approval 
of the medical monitor, provided that the procedure meets the Protocol-defined criteria and has 
been performed in the timeframe of the study.  Assessments that are required to demonstrate 
eligibility may be performed over the course of 1 or more days during the screening process. 
Results from the screening visit evaluations will be reviewed to confirm subject eligibility before 
enrollment.  Tests with results that fail eligibility requirements may be repeated once during 
screening if the investigator believes the results to be in error.  For screening assessments that are 
repeated, the most recent available result before enrollment will be used to determine subject 
eligibility.  Additionally, a subject who fails screening may repeat the screening process 1 time if 
the investigator believes there has been a change in eligibility status (eg, after recovery from an 
infection).  Treatment should start as soon as possible after the date of enrollment. 


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6.2. 
Treatment 
The treatment period begins on the day the subject receives the first dose of study treatment 
(Cycle 1 Day 1) through the point at which the investigator determines that the subject will be 
permanently discontinued from study treatment, or for up to 24 months from the first dose of 
study treatment, whichever occurs first.  Cycle 1 Day 1 must be no more than 28 days after the 
subject has signed the ICF and should be within 3 days of enrollment in the study.  Subjects will 
have regularly scheduled study visits as outlined in Table 10 and toxicities will be monitored 
continuously and will be graded using the NCI CTCAE v4.03 criteria. 
6.3. 
End of Treatment 
When the subject permanently discontinues study treatment, the EOT visit should be conducted.  
If the EOT visit coincides with a regular study visit, the EOT evaluations will supersede those of 
that scheduled visit, and the data should be entered in the EOT visit in the eCRF.  The subject 
should be encouraged to return for the safety and survival follow-up visits. 
Note:  As of Protocol Amendment 5, subjects who permanently discontinue study treatment will 
no longer be followed for survival beyond the last safety follow-up visit. 
6.4. 
Follow-Up 
6.4.1. 
Safety Follow-Up 
The safety follow-up period is the interval between the EOT visit and the scheduled follow-up 
visit, which should occur 30 days (+ 7 days) and 60 days (+ 7 days) after the last dose of study 
treatment.  Monitoring for the occurrence of new AEs should be continued for at least 60 days 
after the last dose of study treatment or until the start of new anticancer therapy, whichever 
occurs first.  Reasonable efforts should be made to have the subject return for the follow-up 
visits and report any AEs that may occur during this period.  If a subject is scheduled to begin a 
new anticancer therapy before the end of the 30-day or 60-day safety follow-up period, the safety 
follow-up visit should be performed before new anticancer therapy is started.  Once new 
anticancer therapy has been initiated, AEs and SAEs will no longer be collected, and the subject 
will move into the survival follow-up period. 
Note:  As of Protocol Amendment 5, the safety follow-up visits will include AE and concomitant 
medication assessment only and may be completed remotely (such as by televisit). 
Note:  As of Protocol Amendment 5, if a new anticancer therapy has been initiated before the 
end of the safety follow-up period, no further survival follow-up assessment will be required 
beyond the last safety follow-up visit. 
6.4.2. 
Disease Status Follow-Up 
Subjects who discontinue study treatment for a reason other than disease progression 
(eg, toxicity) will move into the disease status follow-up period and should be assessed every 
8 weeks (± 7 days), for 12 months.  After 12 months, radiologic assessments will be performed 
every 12 weeks until disease progression is determined.  Every effort should be made to collect 
information regarding disease status until: 


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• The start of new antineoplastic therapy. 
• Disease progression. 
• Death. 
• The end of the study. 
• Withdrawal of consent. 
Note:  As of Protocol Amendment 5, disease status follow-up will no longer be required beyond 
the last safety follow-up visit for subjects who discontinue study treatment for a reason other 
than disease progression.  The last disease status follow-up data will be recorded in the eCRF at 
the time of the last safety follow-up visit.  The last study visit will be the last safety follow-up 
visit. 
6.4.3. 
Survival Follow-Up 
Once a subject has received the last dose of study treatment, confirmed disease progression, or 
starts a new anticancer therapy, the subject moves into the survival follow-up period and should 
be contacted by telephone, email, or visit at least every 12 weeks (+ 7 days) to assess for survival 
status until death, withdrawal of consent, or the end of the study, whichever occurs first. 
Note:  As of Protocol Amendment 5, survival follow-up will no longer be required beyond the 
last safety follow-up visit for subjects who have confirmed disease progression or start a new 
anticancer therapy.  The last survival follow-up data will be recorded in the eCRF at the time of 
the last safety follow-up visit.  The last study visit will be the last safety follow-up visit. 
6.5. 
End of Study 
The end of the study will occur when all subjects have completed the last study follow-up visit or 
have discontinued study treatment and have completed applicable follow-up assessments.  
Additionally, subjects will be considered as having completed the study if they meet any of the 
following criteria: 
• Subject dies and a date of death is available. 
• Subject is known to have died; however, the date of death cannot be obtained.  
(NOTE:  Every effort must be made to obtain the date of death.) 
• Consent is withdrawn for any further contact related to this study. 
− Every reasonable effort should be made to determine the reason a subject 
withdraws prematurely, and this information should be recorded in the eCRF. 
• The study is terminated by the sponsor. 
• The study is terminated by the local health authority or IRB or IEC. 
6.6. 
Unscheduled Visits 
Unscheduled study visits may occur at any time if medically warranted.  Any assessments 
performed at those visits should be recorded in the eCRF. 


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7. 
CONDUCT OF STUDY ASSESSMENTS AND PROCEDURES 
Individual study procedures are described in detail below.  It may be necessary to perform these 
procedures at unscheduled timepoints if deemed clinically necessary by the investigator.  
Furthermore, additional evaluations/testing may be deemed necessary for reasons related to 
subject safety.  In some cases, such evaluation/testing may be potentially sensitive in nature 
(eg, HIV, HCV), and thus local regulations may require that additional informed consent be 
obtained from the subject.  In these cases, such evaluations/testing will be performed in 
accordance with those regulations.  Per Section 3.1, subjects of childbearing potential must agree 
to take appropriate measures to avoid pregnancy in order to participate in the study 
(Appendix A). 
7.1. 
Administration of Informed Consent Form 
Valid informed consent must be obtained from the study subject before conducting any 
study-specific procedures using an ICF approved by the local IRB/IEC that contains all elements 
required by ICH E6 and describes the nature, scope, and possible consequences of the study in a 
form understandable to the study subject.  Additional consent may also be required per local 
regulatory agencies.  Local and institutional guidelines for ICF content and administration must 
be followed; the original signed ICF must be retained by the investigator, and a copy of the 
signed ICF must be provided to the study subject.  The informed consent process for each subject 
must be documented in writing within the subject source documentation. 
7.2. 
Interactive Response Technology System Procedure 
The site will contact the IRT to obtain a subject identification number when a subject enters the 
prescreening phase.  Upon determining that the subject is eligible for study entry, the IRT will be 
contacted to obtain the treatment group assignment.  Additionally, the IRT will be contacted to 
update the subject's disposition, disease response, and for study drug resupply.  Refer to the IRT 
manual for detailed instructions.   
During Phase 2 of the study, the IRT system will be updated based on the PoS calculations 
discussed in Section 9.6.  Probability of success calculations will be performed based on 
response data available within the IRT system and treatment groups may be closed to subject 
assignment if the PoS for a treatment group-tumor type combination is below the futility 
threshold.  Subjects will be assigned sequentially to treatment groups that are open to assignment 
based on these PoS calculations.  Periodically, the sponsor will review the disease response data 
within the IRT system for consistency with the clinical database and request changes to resolve 
discrepancies. 


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7.3. 
Demography and Medical History 
7.3.1. 
Demographics and General Medical History 
Demographic data and a complete medical and medication history will be collected at screening 
by the investigator or qualified designee and will include date of birth, race, ethnicity, medical 
and surgical history, and current illnesses.  Medical history will include relevant medical or 
surgical treatment within the last 10 years that are considered to be clinically significant by 
the investigator. 
7.3.2. 
Disease Characteristics and Treatment History 
A disease-targeted medical and medication history will be collected at screening.  Details 
regarding the subject's malignancy under study including date of diagnosis, initial and current 
cancer stage, tumor histology, relevant disease characteristics, and prior treatments including 
systemic, radiation, and surgical procedures will be recorded. 
7.4. 
Prior and Concomitant Medications and Procedures 
Prior and concomitant medications and procedures will be reviewed to determine subject 
eligibility.  Any medication received or procedure performed within 28 days before the first dose 
of study treatment, up to the end of the safety follow-up phase, or until the subject starts a new 
anticancer therapy, whichever occurs first, will be recorded in the eCRF.  The medication record 
will be maintained after signing the ICF to document concomitant medications, including any 
changes to the dose or regimen.  Concomitant medications include any prescription, 
over-the-counter, or natural/herbal preparations taken or administered during the study period.  
Concomitant treatments and/or procedures that are required to manage a subject's medical 
condition during the study will also be recorded in the eCRF.  See Section 5.6 for details 
regarding restricted and prohibited medications. 
7.5. 
Poststudy Anticancer Therapy Status 
The investigator or qualified designee will review all new anticancer therapy initiated after the 
last dose of study treatment.  If a subject initiates a new anticancer therapy within 30 to 60 days 
after the last dose of study treatment, the 30-day or 60-day safety follow-up visit should occur 
before the first dose of the new anticancer therapy. 
Note:  As of Protocol Amendment 5, information on new anticancer therapy will no longer be 
collected beyond the last safety follow-up visit. 
7.6. 
Safety Assessments 
Nivolumab and ipilimumab are approved therapies; therefore, the investigator should refer to and 
follow the safety management guidelines as appropriate within the approved package insert for 
both compounds. 


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7.6.1. 
Adverse Events 
Adverse events will be monitored from the time the subject signs the ICF.  Subjects will be 
instructed to report all AEs during the study and will be assessed for the occurrence of AEs 
throughout the study.  In order to avoid bias in eliciting AEs, subjects will be asked general, 
nonleading questions such as "How are you feeling?"  All AEs (serious and nonserious) must be 
recorded on the source documents and eCRFs regardless of the assumption of a causal 
relationship with the study drug.  The definition, reporting, and recording requirements for AEs 
are described in Section 8. 
7.6.2. 
Physical Examinations 
Physical examinations must be performed by a medically qualified individual such as a licensed 
physician, physician's assistant, or an advanced registered nurse practitioner, as local law 
permits.  Clinically notable abnormalities that are considered clinically significant in the 
judgement of the investigator are to be reported as AEs. 
7.6.2.1. 
Comprehensive Physical Examination 
The comprehensive physical examination will include assessment(s) of the following organ or 
body systems:  skin; head, eyes, ears, nose, and throat; thyroid; lungs; cardiovascular system; 
abdomen (liver, spleen); extremities; and lymph nodes, as well as a brief neurological 
examination.  The screening physical examination should also include a measurement of height. 
7.6.2.2. 
Targeted Physical Examination 
The targeted physical examination will be a symptom-directed evaluation conducted by the 
investigator or a medically qualified designee.  The targeted physical examination will include 
assessment(s) of the body systems or organs, as indicated by subject symptoms, AEs, or other 
findings.   
7.6.3. 
Vital Signs 
Vital sign measurements include blood pressure, pulse, respiratory rate, and body temperature.  
Blood pressure and pulse will be taken with the subject in the recumbent, semirecumbent, or 
sitting position after 5 minutes of rest.  Weight will also be assessed at each study visit.  
Clinically notable abnormalities that are considered clinically significant in the judgment of the 
investigator are to be reported as AEs.   
7.6.4. 
Electrocardiograms 
All 12-lead ECGs will be performed at the study site with the subject in a recumbent or 
semirecumbent position after 5 minutes of rest as outlined in Table 10. 
The 12-lead ECG readings will be interpreted by the investigator at the site to be used for 
immediate subject management.  Additional 12-lead ECGs may be performed as clinically 
indicated, or as per the nivolumab prescribing instructions, to manage subject safety.  The 
decision to include or exclude a subject or withdraw a subject from the study treatment based on 
an ECG flagged as "Abnormal, Clinically Significant" is the responsibility of the investigator, in 
consultation with the medical monitor, as appropriate.  Clinically notable abnormalities that are 
considered clinically significant in the judgment of the investigator are to be reported as AEs.  


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In the event that a single QTc is > 470 milliseconds at screening, the subject may enroll if the 
average QTc for the 3 ECGs is < 470 milliseconds or with approval from the medical monitor.  
For subjects with an intraventricular conduction delay (QRS interval > 120 milliseconds) at 
screening, the JTc interval may be used in place of the QTc with medical monitor approval.  In 
addition, the JTc interval should be used for all subsequent assessments. 
7.6.5. 
Laboratory Assessments 
A certified laboratory local to the study site and subject will perform all clinical laboratory 
assessments for safety (ie, blood chemistries, hematology assessments, coagulation tests, 
endocrine function, and urinalysis).  The investigative site will enter the laboratory results and 
laboratory normal ranges into the eCRF.  All local laboratory assessments should be performed 
using standard procedures on the days indicated in Table 11.  Table 12 lists the specific 
laboratory analytes required for each test.  Additional testing may be required by the sponsor 
based on emerging safety data.  Additional tests may also be performed if clinically indicated. 
Screening laboratory assessments must be performed within 7 days of Cycle 1 Day 1.  If 
performed more than 7 days before Cycle 1 Day 1, then the tests must be repeated and eligibility 
confirmed before study drug administration on Cycle 1 Day 1.  Laboratory samples collected on 
study Day 1 must be performed before study drug administration.  After Cycle 1, predose 
laboratory procedures can be conducted up to 72 hours before study drug administration (within 
the 3-day study window), and results should be reviewed by the investigator or qualified 
designee and found to be acceptable before a new cycle of treatment is initiated. 
7.6.5.1. 
Pregnancy Testing 
A local laboratory serum pregnancy test will be required for all women of childbearing potential 
during screening and at EOT.  The serum pregnancy test performed at screening must be 
performed within 72 hours before the first dose of study drug.  Urine pregnancy tests will be 
performed locally as outlined in Table 11, as medically indicated (eg, in case of loss of menstrual 
cycle, when pregnancy is suspected), or per country-specific requirements (note that 
country-required urine  pregnancy testing will be outlined and communicated to investigational 
sites under separate cover).  If a urine pregnancy test is positive, then the results should be 
confirmed with a serum pregnancy test. 
If the serum pregnancy test is negative after a urine test was positive, then the investigator will 
assess the potential benefit/risk to the subject and determine whether it is in the subject's best 
interest to resume study treatment and continue participation in the study. 
7.6.5.2. 
Hepatitis Screening Tests 
Hepatitis screening assessments will be performed at the screening visit (Table 11) to rule out 
hepatitis infection; required analytes are shown in Table 12.  Generally, hepatitis tests should be 
performed early in the screening process due to the length of time needed to obtain the results.  
Additional tests may be performed if clinically indicated. 


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7.7. 
Efficacy Assessments 
7.7.1. 
Modified RECIST v1.1 Assessment Disease 
Modified RECIST will be applied by the site as the primary measure for assessment of tumor 
response and as a basis for Protocol guidelines related to disease status (eg, discontinuation of 
study therapy).  As noted in Section 1.5.4.1, RECIST v1.1 has been adapted to account for the 
unique tumor responses seen with immunotherapy (Wolchok et al 2009). 
If radiologic imaging shows progressive disease, tumor assessment should be repeated at a 
minimum of 4 weeks, but no later than 6 weeks later to confirm progression, with the option of 
continuing treatment while awaiting radiologic confirmation of progression.  Table 13 provides 
instructions on how to proceed with treatment based on the subject's clinical status once the 
initial scan showing radiologic evidence of progression is observed. 
Subjects may receive treatment while waiting for confirmation of progression if they are 
clinically stable as defined by the following criteria: 
• Absence of clinically significant signs and symptoms (including worsening of 
laboratory values) indicating disease progression. 
• No decline in ECOG performance status. 
• Absence of rapid progression of disease. 
• Absence of progressive tumor at critical anatomical sites (eg, cord compression) 
requiring urgent alternative medical intervention. 
Table 13: 
Imaging and Treatment After First Radiologic Evidence of Progressive 
Disease 
 
Clinically Stable 
Clinically Unstable 
Tumor Imaging 
Treatment 
Tumor Imaging 
Treatment 
First radiologic 
evidence of 
progression 
Repeat imaging 
4-6 weeks to confirm 
progression 
May continue study 
treatment at the 
investigator's discretion 
while awaiting 
confirmatory tumor 
imaging  
Repeat tumor imaging 
4-6 weeks to confirm 
progression per 
physician discretion 
only 
Discontinue 
treatment 
Repeat scan  
confirms 
progression 
No additional tumor 
imaging required 
Discontinue treatment 
No additional tumor 
imaging required 
N/A 
Repeat scan 
shows SD, PR, 
or CR 
Continue regularly 
scheduled tumor 
imaging assessments 
Continue study treatment 
at the investigator's 
discretion 
Continue regularly 
scheduled tumor 
imaging assessments 
May restart study 
treatment if 
condition has 
improved and/or 
clinically stable per 
investigator's 
discretion 




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7.7.1.1.2. Tumor Imaging During the Study 
The first imaging assessment should be performed 8 weeks after the first dose of 
INCAGN01876 and then every 8 weeks (56 days ± 7 days), for 12 months and then every 
12 weeks thereafter until disease progression is determined.  Imaging assessments may be 
done more frequently if clinically indicated.  Imaging should not be delayed for delays in 
cycle starts. 
Per mRECIST v1.1, response should be confirmed by a repeat radiographic assessment not less 
than 4 weeks from the date the response was first documented.  The scan for confirmation of 
response may be performed at the earliest 4 weeks after the first indication of response or at the 
next scheduled scan, whichever is clinically indicated. 
Imaging should continue to be performed until documented disease progression, the start of new 
anticancer treatment, withdrawal of consent, death, or the end of the study, whichever occurs 
first.  Disease progression should be confirmed at least 4 weeks, but no later than 6 weeks, after 
the first scan indicating progression in clinically stable subjects.  Subjects who have unconfirmed 
disease progression may continue on treatment until progression is confirmed, provided that they 
have met the conditions detailed in Section 7.7.1.  A central imaging vendor will not be used in 
this study. 
7.7.1.1.3. Imaging During Follow-Up 
If the subject discontinues study treatment for reasons other than disease progression, imaging 
assessments should continue at the Protocol-specified interval until documented disease 
progression, the start of new anticancer treatment, withdrawal of consent, death, or the end of the 
study, whichever occurs first. 
Note:  As of Protocol Amendment 5, follow-up imaging to monitor disease status is no longer 
required beyond the last safety follow-up visit (see Section 6.4.2) for subjects who discontinue 
study treatment for reasons other than disease progression. 
7.8. 
Performance and Quality-of-Life Assessments 
7.8.1. 
Eastern Cooperative Oncology Group Performance Status 
The ECOG performance status will be assessed as shown in Table 10 according to the criteria in 
Table 14. 










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7.11. 
Other Study Procedures 
7.11.1. 
Distribution of Subject Reminder Cards 
Subjects will be provided with a reminder card at each visit.  The subject reminder cards will 
remind the subject of the date/time of the next visit, as well as any necessary instructions.   
7.11.2. 
Data Collection for Survival Follow-Up 
For subjects having entered the survival follow-up period of the study, the site will use 
continuing subject records to supply data on subsequent treatment regimens, tumor assessments 
(if discontinued treatment for a reason other than progression), and OS in the eCRF.  For subjects 
who do not intend to return to the study investigator for their ongoing care, follow-up should be 
maintained by phone contact, patient records, and public records/databases at intervals of no 
longer than 12 weeks.  After the final primary analysis is performed, the follow-up interval for 
subsequent anticancer treatments and survival may be reduced to every 16 weeks or eliminated 
(see Section 6.4.3). 
Note:  As of Protocol Amendment 5, data collection for survival follow-up is no longer required 
beyond the last safety follow-up visit.  The last survival follow-up data will be recorded in the 
eCRF at the time of the last safety follow-up visit. 


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8. 
SAFETY MONITORING AND REPORTING 
8.1. 
Adverse Events 
8.1.1. 
Definitions 
For the purposes of this Protocol, an AE is defined as any untoward medical occurrence 
associated with the use of a drug in humans, whether or not considered drug related, that occurs 
after a subject provides informed consent.  Abnormal laboratory values or test results occurring 
after informed consent constitute AEs only if they induce clinical signs or symptoms, are 
considered clinically meaningful, require therapy (eg, hematologic abnormality that requires 
transfusion), or require changes in the study drug(s). 
8.1.2. 
Reporting 
Adverse events that begin or worsen after informed consent should be recorded on the Adverse 
Events form of the eCRF.  Conditions that were already present at the time of informed consent 
should be recorded on the Medical History form in the eCRF.  Monitoring for the occurrence of 
new AEs should be continued for at least 60 days after the last dose of study treatment or until 
the start of new anticancer therapy, whichever occurs first.  Adverse events (including laboratory 
abnormalities that constitute AEs) should be described using a diagnosis whenever possible 
rather than by individual underlying signs and symptoms.   
The disease/disorder being studied, or expected progression, signs, or symptoms of the 
disease/disorder being studied, should not be reported as an AE/SAE unless it is considered more 
severe than expected for the participant's condition or considered to be treatment-related by the 
investigator.  Additionally, efficacy endpoints as outlined in Section 2.2 will not be reported as 
AE/SAEs, specifically, any event that is related to disease progression of the cancer under study.  
Unblinded aggregated efficacy endpoint events and safety data will be monitored to ensure the 
safety of the subjects in the study.  Any suspected endpoint that upon review is not progression 
of the cancer under study will be forwarded to Incyte Pharmacovigilance as an SAE within 
24 hours of determination that the event is not progression of the cancer under study. 
The severity of AEs will be assessed using CTCAE v4.03 Grades 1 through 5.  If an event is not 
classified by CTCAE, the severity of the AE will be graded according to the scale below to 
estimate the grade of severity: 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
Grade 2 
Moderate; minimal, local, or noninvasive intervention indicated; limiting 
age-appropriate activities of daily living. 
Grade 3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care activities of daily living. 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 
Death due to AE 


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The occurrence of AEs should be sought by nondirective questioning of the subject during the 
screening process after signing the ICF and at each visit during the study.  Adverse events may 
also be detected when they are volunteered by the subject during the screening process or 
between visits, or through physical examination, laboratory test, or other assessments.  To the 
extent possible, each AE should be evaluated to determine: 
• The severity grade (CTCAE Grade 1 to 5). 
• Whether there is at least a reasonable possibility that the AE is related to the study 
treatment:  suspected (yes) or not suspected (no). 
− Note:  causality assessment for each agent administered per study must be 
indicated. 
• The start and end dates, unless unresolved at final follow-up. 
• The action taken with regard to study drug. 
• The event outcome (eg, not recovered/not resolved, recovered/resolved, 
recovering/resolving, recovered/resolved with sequelae, fatal, unknown). 
• The seriousness, as per SAE definition provided in Section 8.3.1. 
Unlike routine safety assessments, SAEs are monitored continuously and have special reporting 
requirements (see Section 8.3.2). 
All AEs should be treated appropriately.  If an AE is treated with a concomitant medication or 
nondrug therapy, this action should be recorded on Adverse Event form and the treatment should 
be specified on the Prior/Concomitant Medications or Procedures and Non-Drug Therapy form 
in the eCRF. 
Once an AE is detected, it should be followed until it has resolved or until it is judged to be 
permanent; assessment should be made at each visit (or more frequently if necessary) of any 
changes in severity, the suspected relationship to the study drug, the interventions required to 
treat the event, and the outcome. 
When the severity of an AE changes over time for a reporting period (eg, between visits), each 
change in severity will be reported as a separate AE until the event resolves.  For example, 
2 separate AEs will be reported if a subject has Grade 1 diarrhea, meeting the definition of an 
AE, that lasts for 3 days before worsening to a Grade 3 severity.  The Grade 1 event will be 
reported as an AE with a start date equal to the day the event met the Grade 1 AE definition and 
a stop date equal to the day that the event increased in severity from Grade 1 to Grade 3.  The 
Grade 3 event will also be reported as an AE, with the start date equal to the day the event 
changed in intensity from Grade 1 to Grade 3 and a stop date equal to the day that the event 
either changed severity again or resolved. 


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8.2. 
Laboratory Test Abnormalities 
Laboratory abnormalities that constitute an AE in their own right (considered clinically 
meaningful, induce clinical signs or symptoms, require concomitant therapy, or require 
interruption of study treatment) should be recorded on the Adverse Event form in the eCRF.  
Whenever possible, a diagnosis rather than a symptom should be provided (eg, "anemia" instead 
of "low hemoglobin").  Laboratory abnormalities that meet the criteria for AEs should be 
followed until they have returned to normal or an adequate explanation of the abnormality is 
found.  When an abnormal laboratory test result corresponds to a sign or symptom of a 
previously reported AE, it is not necessary to separately record the laboratory test result as an 
additional event. 
Laboratory abnormalities that do not meet the definition of an AE should not be reported as AEs.  
A Grade 3 or 4 (severe) AE does not automatically indicate an SAE unless it meets the definition 
of serious, as defined in Section 8.3.1.  A dose modification for the laboratory abnormality may 
be required (see Section 5.4) and should not contribute to the designation of a laboratory test 
abnormality as an SAE. 
8.3. 
Serious Adverse Events 
8.3.1. 
Definitions 
An SAE is defined as an event that meets at least 1 of the following criteria: 
• Is fatal or life-threatening. 
• Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is a result of: 
− A routine treatment or monitoring of the studied indication not associated with 
any deterioration in condition.  
− An elective surgery or preplanned treatment for a pre-existing condition that is 
unrelated to the indication under study and has not worsened since signing the 
ICF. 
− A treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE and not resulting in hospital admission. 
− Any social reasons and respite care, in the absence of any deterioration in the 
subject's general condition. 
• Results in persistent or significant disability, incapacity, or a substantial disruption of 
a person's ability to conduct normal life functions. 
• Constitutes a congenital anomaly or birth defect. 
• Is considered to be an important medical event or a medically significant event that 
may not result in death, be immediately life-threatening, or require hospitalization but 
may be considered serious when, based on appropriate medical judgment, the event 
may jeopardize the subject or may require medical or surgical intervention to prevent 
1 of the outcomes listed above. 


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8.3.2. 
Reporting 
Every SAE, regardless of suspected causality (eg, relationship to study drug(s) or study 
procedure or disease progression), occurring after the subject has signed the ICF through the last 
study visit (or 60 days after the last dose of study treatment, or until the subject receives a new 
anticancer therapy whichever occurs earlier) must be reported to the sponsor (or designee) within 
24 hours of learning of its occurrence, unless otherwise specified by the Protocol.  Any SAEs 
occurring more than 60 days after the last dose of study treatment should be reported to the 
sponsor or its designee only if the investigator suspects a causal relationship to the study drug.   
Information about all SAEs is collected and recorded on the Adverse Event form of the eCRF.  
The investigator must assess and record the causal relationship of each SAE to each specific 
study treatment.  The investigator must also complete the Incyte Serious Adverse Event Report 
Form, in English, and send the completed and signed form to the sponsor or designee within 
24 hours of becoming aware of the SAE.  The investigator must provide a causality assessment, 
that is, assess whether there is at least a reasonable possibility that the SAE is related to the 
specific study treatment:  suspected (yes) or not suspected (no).  Refer to the Incyte Reference 
Guide for Completing the Serious Adverse Event Report Form. 
The contact information of the sponsor's study-specific representatives is listed in the 
investigator manual provided to each site.  The original copy of the SAE Report Form and the 
confirmation sheet must be kept at the study site. 
Investigational site personnel must report any new information regarding the SAE within 
24 hours of becoming aware of the information in the same manner that the initial SAE Report 
Form was sent.  Follow-up information is recorded on an amended or new SAE Report Form, 
with an indication that it is follow-up to the previously reported SAE and the date of the original 
report.  The follow-up report should include information that was not provided on the previous 
SAE Report Form, such as the outcome of the event (eg, resolved or ongoing), treatment 
provided, action taken with study drug because of the SAE (eg, dose interrupted or 
discontinued), or subject disposition (eg, continued or withdrew from study participation).  Each 
recurrence, complication, or progression of the original event should be reported as follow-up to 
that event. 
If the SAE is not documented in the IB for the study drug (new occurrence) and is thought to be 
related to the sponsor's study drug, the sponsor or its designee may urgently require further 
information from the investigator for reporting to health authorities.  The sponsor or its designee 
may need to issue an Investigator Notification to inform all investigators involved in any study 
with the same drug that this SAE has been reported.  Suspected Unexpected Serious Adverse 
Reactions will be collected and reported to the competent authorities and relevant ethics 
committees in accordance with Directive 2001/20/EC, or as per national regulatory requirements 
in participating countries. 
8.4. 
Emergency Unblinding of Treatment Assignment 
Not applicable. 


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8.5. 
Pregnancy 
Pregnancy, in and of itself, is not regarded as an AE unless there is suspicion that study drug may 
have interfered with the effectiveness of a contraceptive medication or method.  When a 
pregnancy has been confirmed in a subject during maternal or paternal exposure to study drug, 
the following procedures should be followed in order to ensure subject safety: 
• The study treatment must be discontinued immediately (female subjects only). 
• The investigator must complete and submit the Incyte Clinical Trial Pregnancy form 
to the sponsor or its designee within 24 hours of learning of the pregnancy. 
• A serum pregnancy test must be performed to confirm the urine pregnancy test result.  
If a negative serum test does not confirm the urine pregnancy result, then: 
− The investigator will use his or her expert judgment, based on an assessment of 
the potential benefit/risk to the subject, to determine whether it is in the subject's 
best interest to resume study treatment and continue participation in the study. 
• The EOT visit evaluations must be performed. 
Data on fetal outcome and breastfeeding are collected for regulatory reporting and drug safety 
evaluation.  Follow-up should be conducted for each pregnancy to determine outcome, including 
spontaneous or voluntary termination, details of the birth, and the presence or absence of any 
birth defects, congenital abnormalities, or maternal and/or newborn complications, by following 
until the first well-baby visit.  Pregnancy should be recorded on a Clinical Trial Pregnancy form 
and reported by the investigator to the sponsor or its designee.  Pregnancy follow-up information 
should be recorded on the same form and should include an assessment of the possible causal 
relationship to the sponsor's study drug to any pregnancy outcome, as well as follow-up to the 
first well-baby visit or the duration specified in local regulations, whichever is later.  Refer to the 
Incyte Reference Guide for Completing the Clinical Trial Pregnancy Form. 
Any SAE occurring during pregnancy must be recorded on the SAE report form and 
submitted to the sponsor or designee. 
8.6. 
Warnings and Precautions 
Special warnings or precautions for the study drug, derived from safety information collected by 
the sponsor or its designee, are presented in the Investigator's Brochure.  Additional safety 
information collected between IB updates will be communicated in the form of Investigator 
Notifications.  Any important new safety information should be discussed with the subject during 
the study, as necessary.  If new significant risks are identified, they will be added to the ICF. 


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8.7. 
Data Monitoring Committee 
Formal safety data reviews will be conducted by the study team (eg, medical monitor, clinical 
scientist, and biostatistician) and an independent internal review committee at least every 
6 months.  Details regarding data monitoring will be addressed in the Data Safety Monitoring 
Charter. 
8.8. 
Product Complaints 
The sponsor collects product complaints on study drugs and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements. 
All product complaints associated with material packaged, labeled, and released by the sponsor 
or its designee will be reported to the sponsor.  All product complaints associated with other 
study material will be reported directly to the respective manufacturer. 
The investigator or his/her designee is responsible for reporting a complete description of the 
product complaint via email or other written communication to the sponsor contact or respective 
manufacturer as noted in the packaging information.  Any AE associated with a product 
complaint should be reported as described in Section 8.1.2 of this Protocol. 
If the investigator is asked to return the product for investigation, he/she will return a copy of the 
product complaint communication with the product. 




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Table 18: 
Probability of Dose Escalation for Various DLT Rates 
True DLT Rate 
Probability of Dose Escalation 
20% 
78.4% 
30% 
56.1% 
40% 
35.0% 
50% 
18.9% 
60% 
8.8% 
For example, if the true DLT rate is 50% at a given dose level, there is an 18.9% chance that the 
dose would be escalated.  Further, if the true DLT rate is 20%, there is a 78.4% chance that the 
dose would be escalated.  If the MTD is not determined at the highest dose level tested during 
the study, then the MTD is at or above the highest dose level.  The MTD is below the lowest 
dose level of INCAGN01876 if the Cohort 1 dose is not well-tolerated. 
9.2.2. 
Sample Size for Phase 2 
Phase 2 will further evaluate the safety, tolerability, preliminary efficacy, 
 
 of the recommended dose of INCAGN01876 in combination with immune therapies as 
part of doublet and triplet drug expansion cohorts.  In Phase 2, a Simon 2-stage design will be 
run for the cervical cancer, gastric cancer, SCCHN and PD-1/PD-L1 relapsed melanoma cohorts 
within a given doublet or triplet treatment group.  A Simon 2-stage design with an expansion 
stage will be used for the PD-1 refractory SCCHN cohort. 
The sample size for each tumor type within a given doublet or triplet expansion cohort will be 
guided by the Simon 2-stage design (except for the PD-1 refractory SCCHN cohort in Treatment 
Group F).  The planned Simon 2-stage designs are summarized in Table 19.  Each Simon 2-stage 
design will have a stopping rule to allow early termination of a particular tumor type within the 
given treatment combination at the end of Stage 1 if there is insufficient response observed 
(calculated response rate < p0), while enrolling enough subjects to predict possible target 
responses (≥ p1) worthy of cohort expansion and potentially further evaluation in future studies.  
The individual Simon 2-stage designs run for each tumor type within each doublet or triplet 
expansion cohort will have design parameters that are determined by historical response rates.  
The same Simon 2-stage design parameters will be used for alternative dosing sequences in the 
same tumor type and treatment combination.  For example, the gastric cohorts in Treatment 
Groups F, G, and H will all use the same Simon 2-stage parameters. 
In order to determine whether the target response rate (p1) is likely, an initial number of 
evaluable subjects (n1 subjects) treated at the MTD or PAD and schedule of INCAGN01876 
within the corresponding doublet or triplet expansion cohort will be enrolled in a cohort 
(Stage 1).  If there are r1 or fewer responses in the cohort, it will be concluded that the true 
response rate is unlikely to be greater than or equal to the target rate, and no more subjects will 
be enrolled in that tumor type in Stage 2.  In the cohorts in which greater than r1 responses are 
observed among the Stage 1 subjects, n2 additional evaluable subjects will be treated in Stage 2 
to estimate the response rate.  At the end of Stage 2, if ≤ r subjects have responded among the n 
evaluable subjects, the doublet or triplet schedule will be declared nonpromising for that cohort.  




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Table 20: 
Planned Simon 2-Stage Design with Expansion Stage for PD-1 Refractory 
SCCHN Cohort in Phase 2 
Indication 
Combination 
r1 
n1 
r2 
n2 
r 
n3 
n 
p0 
p1 
PD-1 refractory SCCHN 
GITR + Nivo 
0 
12 
3 
25 
6 
20 
57 
5% 
20% 
Note:  The definitions of p0, p1, r1, n, n1, and n2 are the same as those in Table 19. 
r2:  If r2 or fewer responses are observed by the end of Stage 2, the study cohort is stopped early for futility. 
r:  If r or fewer responses are observed by the end of expansion stage, then no further investigation of the drug combination is 
warranted in the study cohort. 
n3:  Number of subjects enrolled in the expansion stage. 
9.3. 
Level of Significance 
For the primary efficacy endpoints, the 1-sided Type I error will be controlled at 0.05 for each 
individual cohort expansion.  Note that this level of significance does not account for the 
multiple expansion cohorts.  For other endpoints, confidence intervals will be reported at a 95% 
confidence level. 
9.4. 
Statistical Analyses 
9.4.1. 
Efficacy Analyses 
9.4.1.1. 
Primary Efficacy Analyses 
In Phase 2, the proportion of subjects who meet the objective response criteria (CR + PR) per 
RECIST v1.1 will be summarized by tumor type. 
For the cohorts using a Simon 2-stage design, if there are no responses in each tumor type–
specific doublet or triplet treatment group out of the n1 evaluable subjects specific to that tumor 
type–specific doublet or triplet treatment group (consistent with a calculated response rate < p0) 
at Stage 1, then the study will be stopped for futility, and the null hypothesis is not rejected.  
Otherwise, in the tumor types in which greater than r1 responses among the evaluable Stage 1 
subjects is observed, where r1 is also specific to the tumor type and doublet or triplet expansion 
cohort, an additional n2 evaluable subjects will be treated in Stage 2.  If there are ≤ r responders 
among the evaluable subjects at the end of Stage 2, then the drug will be declared nonpromising 
for that tumor type within the given doublet or triplet expansion cohort, and the null hypothesis 
is not rejected.  Further investigation of the study drug will be considered interesting (predictive 
of ≥ p1 response rate) if > r responses are observed in the first n evaluable subjects.   
For the PD-1 refractory SCCHN cohort using a Simon 2-stage design with an expansion stage, if 
there is an insufficient number of responses observed at the end of Stage 1 or Stage 2, the cohort 
will be terminated early for futility.  If the number of responders observed is > r1 for Stage 1 and 
> r2 for Stage 2, an additional number of evaluable subjects needed for the next stage (n2 and n3, 
respectively) will be enrolled.  At the end of the expansion stage, if the number of responders 
observed is ≤ r among the n evaluable subjects, then the drug will be declared nonpromising for 
the PD-1 refractory SCCHN cohort.  If > r responders are observed, the drug will be declared 
promising for further investigation. 


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For the hypothesis tests in the Simon 2-stage design and Simon 2-stage design with expansion 
stage, the null response rate is p0 and alternative response rate is p1, where p0 and p1 are specific 
to the tumor type within a given doublet or triplet expansion cohort and are determined from 
historical response rates. 
9.4.1.2. 
Secondary Efficacy Analyses 
Disease control rate, defined as the proportion of subjects who have disease control (CR + PR + 
SD), as per RECIST v1.1 and mRECIST v1.1 will be summarized.  
Progression-free survival, DOR, and duration of disease control will be estimated using the 
Kaplan-Meier method as per RECIST v1.1 and mRECIST v1.1.  Overall survival will be 
estimated using the Kaplan-Meier method. 
In Phase 2, the proportion of subjects who meet the objective response criteria (CR + PR) per 
RECIST v1.1 and mRECIST v1.1 will be summarized by tumor type. 
9.4.2. 
Safety Analyses 
9.4.2.1. 
Adverse Events 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after 
first dose of study drug.  Analysis of AEs will be limited to TEAEs, but data listings will include 
all AEs regardless of their timing to study drug administration.  Adverse events will be tabulated 
by the MedDRA preferred term and system organ class.  Severity of AEs will be based on the 
NCI CTCAE v4.03 using Grades 1 through 5. 
The subset of AEs considered by the investigator to have a relationship to study drug will be 
considered to be treatment-related AEs.  If the investigator does not specify the relationship of 
the AE to study drug, the AE will be considered treatment-related.  The incidence of AEs and 
treatment-related AEs will be tabulated. 
9.4.2.2. 
Clinical Laboratory Tests 
Laboratory test values outside the normal range will be assessed for severity based on the normal 
ranges for the clinical reference laboratory.  The incidence of abnormal laboratory values and 
shift tables relative to baseline will be tabulated. 
Laboratory data will be classified into Grades 1 through 5 using CTCAE v4.03.  The following 
summaries will be produced for the laboratory data: 
• Number and percentage of subjects with worst postbaseline CTCAE grade (regardless 
of baseline value).  Each subject will be counted only for the worst grade observed 
postbaseline. 
• Shift tables from baseline to the worst postbaseline value using CTCAE grade. 
• For laboratory parameters where CTCAE grades are not defined, shift tables to the 
worst postbaseline value using the low/normal/high classifications based on 
laboratory reference ranges. 






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9.6.2. 
Integrated Bayesian Futility Analysis 
A second approach to determining whether the treatment is active or not across the cohorts will 
use an integrated Bayesian analysis of tumor and dosing strategies based on Simon et al (2016).  
The integrated Bayesian analysis will be used for the cervical cancer, gastric cancer, and SCCHN 
cohorts.  Pooling is performed within dosing strategies and tumor types to determine if 
INCAGN01876 is active within any of the given dosing strategies, given tumor types, or given 
dosing strategy-tumor type combinations.  The first Bayesian pooling analysis will allow sharing 
of information within a tumor type across dosing strategies based on a joint Bayesian prior.  The 
joint Bayesian prior incorporates the unacceptable and target response rates from the Simon 
2-stage designs with a parameter indicating the prior probability of homogeneity within the 
tumor types, which controls the degree of information sharing.  A separate analysis will allow 
sharing of information for dosing strategies across tumor types using a separate joint Bayesian 
prior.  For this analysis, the joint Bayesian prior incorporates the unacceptable and target 
response rates from the Simon 2-stage designs with a parameter indicating the prior probability 
of homogeneity within the dosing strategies, which controls the degree of information sharing. 
Each time a subject with the tumor type of interest is enrolled, two PoS calculations will be 
performed using the evaluable subjects:  the PoS in tumor type (tumor typei and dosing strategyj), 
PoS1ij, and PoS within dosing strategy (tumor typei and dosing strategyj), PoS2ij. 
Based on the results of the 2 calculated posterior PoS values, a tumor-sequence pair (i,j) will be 
considered open for enrollment if and only if either PoS1ij ≥ 20% or PoS2ij ≥ 20%.  Otherwise the 
tumor-sequence pair will be suspended. 
At the end of the study, overall PoS tests will be performed using both PoS1ij and PoS2ij.  A 
tumor-sequence strategy will be considered successful if either PoS1ij or PoS2ij > 80%. 


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10. 
ETHICAL CONSIDERATIONS AND ADMINISTRATIVE 
PROCEDURES 
10.1. 
Investigator Responsibilities 
This study will be performed in accordance with ethical principles that originate in the 
Declaration of Helsinki and conducted in adherence to the study Protocol; GCPs as defined in 
Title 21 of the US CFR Parts 11, 50, 54, 56, and 312; ICH E6 GCP consolidated guidelines; and 
local regulatory requirements as applicable to the study locations. 
The investigator will be responsible for: 
• Permitting study-related monitoring, sponsor audits, IRB/IEC review, and regulatory 
inspections by providing direct access to source data and other relevant clinical study 
documents. 
− Monitoring:  Qualified representatives of the sponsor or its designee, study 
monitors, will monitor the study according to a predetermined plan.  The 
investigator must allow the study monitors to review any study materials and 
subject records at each monitoring visit. 
− Auditing:  Qualified representatives of the sponsor or its designee may audit the 
clinical study site and study data to evaluate compliance with the Protocol, 
applicable local clinical study regulations, and overall study conduct.  The 
investigator must allow the auditors to review original source records and study 
documentation for all subjects. 
− Regulatory inspection:  Regulatory authorities may conduct an inspection of the 
study and the site at any time during the development of an investigational 
product.  The investigator and staff are expected to cooperate with the inspectors 
and allow access to all source documents supporting the eCRFs and other 
study-related documents.  The investigator must immediately notify the sponsor 
when contacted by any regulatory authority for the purposes of conducting an 
inspection. 
• Obtaining informed consent and ensuring that the study subjects' questions have been 
answered and the subjects fully understand study procedures: 
− Informed consent must be obtained before any study-related procedures are 
conducted, unless otherwise specified by the Protocol. 
− Informed consent must be obtained using the IRB/IEC-approved version in a 
language that is native and understandable to the subject.  A template will be 
provided by the sponsor or its designee.  The sponsor or its designee must review 
and acknowledge the site-specific changes to the ICF template.  The ICF must 
include a statement that the sponsor or its designee and regulatory authorities have 
direct access to subject records. 
• Obtaining approval from the IRB/IEC before the start of the study and for any 
changes to the clinical study Protocol, important Protocol deviations, routine updates, 
and safety information in accordance with institutional requirements and local law. 


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− The investigator is responsible for ensuring that the safety reports provided by the 
sponsor are reviewed and processed in accordance with regulatory requirements 
and with the policies and procedures established by the IRB/IEC. 
• Adhering to the Protocol as described in this document and agreeing that changes to 
the Protocol procedures, with the exception of medical emergencies, must be 
discussed and approved, first, by the sponsor or its designee and, second, by the 
IRB/IEC.  Each investigator is responsible for enrolling subjects who have met the 
specified eligibility criteria. 
• Retaining records in accordance with all local, national, and regulatory laws, but for a 
minimum period of at least 2 years after the last marketing application approval in an 
ICH region and until there are no pending or contemplated marketing applications in 
an ICH region, or if not approved, 2 years after the termination of the test article for 
investigation to ensure the availability of study documentation should it become 
necessary for the sponsor or a regulatory authority to review. 
− The investigator must not destroy any records associated with the study without 
receiving approval from the sponsor.  The investigator must notify the sponsor or 
its designee in the event of accidental loss or destruction of any study records.  If 
the investigator leaves the institution where the study was conducted, the sponsor 
or its designee must be contacted to arrange alternative record storage options. 
− All eCRF data entered by the site (including audit trail), as well as computer 
hardware and software (for accessing the data), will be maintained or made 
available at the site in compliance with applicable record retention regulations.  
The sponsor will retain the original eCRF data and audit trail. 
10.1.1. 
Identification of the Coordinating Principal Investigator 
A coordinating principal investigator will be appointed by the sponsor before the end of the 
study.  As part of his or her responsibilities, the coordinating principal investigator will review 
the final CSR.  Agreement with the final CSR will be documented by the dated signature of the 
coordinating principal investigator. 
10.2. 
Accountability, Handling, and Disposal of Study Drug 
The investigator is responsible for drug accountability at the study site; however, some of the 
drug accountability duties may be assigned to an appropriate pharmacist or other designee.  
Inventory and accountability records must be maintained and readily available for inspection by 
the study monitor and are open to inspection at any time by any applicable regulatory authorities.  
The investigator or designee must maintain records that document: 
• Delivery of study drug to the study site. 
• Inventory of study drug at the site. 
• Lot numbers and/or vial numbers (as applicable) of study drug used to prepare the 
infusion solution. 


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• Subject use of the study drug including pill or unit counts from each supply 
dispensed. 
The investigational product must be used only in accordance with the Protocol.  The investigator 
will also maintain records adequately documenting that the subjects were provided the specified 
study drug.  These records should include dates, quantities, and any available batch or serial 
numbers or unique code numbers assigned to the investigational product and study subjects. 
Completed accountability records will be archived by the site.  The investigator or designee will 
be expected to collect and retain all used, unused, and partially used containers of study drug 
until verified by the study monitor (unless otherwise agreed to by the sponsor).  At the 
conclusion of the study, the investigator or designee will oversee shipment of any remaining 
study drug back to the sponsor or its designee for destruction according to institutional standard 
operating procedures.  If local procedures mandate on-site destruction of investigational supply, 
the site should (where local procedures allow) maintain the investigational supply until the study 
monitor inspects the accountability records in order to evaluate compliance and accuracy of 
accountability by the investigative site.  At sites where the study drug is destroyed before 
monitor inspection, the monitors rely on documentation of destruction per the site SOP. 
10.3. 
Data Management 
Data management will be performed in a validated database via an EDC system.  All data entry, 
verification, and validation will be performed in accordance with the current standard operating 
procedures of the Data Management Department at the sponsor or its designee.  The database 
will be authorized for lock once all defined procedures are completed. 
The investigator will be provided with access to an EDC system so that an eCRF can be 
completed for each subject.  Entries made in the eCRF must be verifiable against source 
documents; if updates to the database are not possible, any discrepancies should be explained 
and documented.  The investigator will be responsible for reviewing all data and eCRF entries, 
and will sign and date the designated forms in each subject's eCRF, verifying that the 
information is true and correct.  The investigator is responsible for the review and approval of all 
query responses. 
Protocol deviations will be identified and recorded in the Protocol Deviation form of the eCRF.  
The study monitor will reference the Monitoring Plan in order to ensure that each issue identified 
is appropriately documented, reported, and resolved in a timely manner in accordance with the 
plan's requirements. 
10.4. 
Data Privacy and Confidentiality of Study Records 
The investigator and the sponsor or its designee must adhere to applicable data protection laws 
and regulations.  The investigator and the sponsor or its designee are responsible for ensuring 
that sensitive personal information is handled in accordance with local data protection laws 
(including but not limited to HIPAA and GDPR) as applicable.  Appropriate consent for 
collection, use and disclosure and/or transfer (if applicable) of personal information must be 
obtained in accordance with local data protection laws. 


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Subject names will not be supplied to the sponsor or its designee.  Only the subject number and 
subject's initials (subject's initials will only be recorded if allowable by local regulations) will be 
recorded in the eCRF, where permitted; if the subject's name appears on any other document 
(eg, laboratory report), it must be obliterated on the copy of the document to be supplied to the 
sponsor or its designee.  Study findings stored on a computer will be stored in accordance with 
appropriate technical and organizational measures as required by local data protection laws.  The 
subjects will be informed that representatives of the sponsor or its designee, IRB or IEC, or 
regulatory authorities may inspect their medical records to verify the information collected, and 
that all personal information made available for inspection will be handled in strictest confidence 
and in accordance with local data protection laws. 
10.5. 
Financial Disclosure 
Before study initiation, all clinical investigators participating in clinical studies subject to FDA 
Regulation Title 21 CFR Part 54 – Financial Disclosure by Clinical Investigators (ie, "covered 
studies") are required to submit a completed Clinical Investigator Financial Disclosure form that 
sufficiently details any financial interests and arrangements that apply.  For the purpose of this 
regulation, "clinical investigator" is defined as any investigator or subinvestigator who is directly 
involved in the treatment or evaluation of research subjects, including the spouse and each 
dependent child of the clinical investigator or subinvestigator.  These requirements apply to both 
US and foreign clinical investigators conducting covered clinical studies. 
Any new clinical investigators added to the covered clinical study during its conduct must also 
submit a completed Investigator Financial Disclosure Form.  During a covered clinical study, 
any changes to the financial information previously reported by a clinical investigator must be 
reported to the sponsor or its designee.  At the conclusion of the covered clinical study, the 
clinical investigators will be reminded of their obligations.  In the event that the clinical 
investigator is not reminded, they nevertheless will remain obligated to report to the sponsor or 
its designee any changes to the financial information previously reported, as well as any changes 
in their financial information for a period of 1 year after completion of the covered clinical study. 
10.6. 
Publication Policy 
By signing the study Protocol, the investigator and his/her institution agree that the results of the 
study may be used by the sponsor, Incyte Biosciences International Sàrl (Incyte), for the 
purposes of national and international registration, publication, and information for medical and 
pharmaceutical professionals.  Study results will be published in accordance with applicable 
local and national regulations.  If necessary, the authorities will be notified of the investigator's 
name, address, qualifications, and extent of involvement.  The terms regarding the publication of 
study results are contained in the agreement signed with the sponsor or its designee.  A signed 
agreement will be retained by the sponsor or its designee. 
The results of this study may be published or presented at scientific meetings.  If this is foreseen, 
the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission.  
This allows the sponsor to protect proprietary information and to provide comments. 
The sponsor will comply with the requirements for publication of study results.  In accordance 
with standard editorial and ethical practice, the sponsor will generally support publication of 


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multicenter studies only in their entirety and not as individual site data.  In this case, a 
coordinating investigator will be designated by mutual agreement. 
Authorship will be determined in line with International Committee of Medical Journal Editors 
authorship requirements and the sponsor's internal publication guidelines. 
10.7. 
Study and Site Closure 
The sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor.  Study sites will be closed upon study 
completion.  A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to: 
• Failure of the investigator to comply with the Protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines. 
• Inadequate recruitment of participants by the investigator. 
• Discontinuation of further study treatment development. 


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APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS 
For Subjects Participating in the Study: 
The following methods that can achieve a failure rate of less than 1% per year when used 
consistently and correctly are considered as highly effective birth control methods.  
Such methods include: 
• Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation1 
− oral 
− intravaginal 
− transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation1 
− oral 
− injectable 
− implantable2 
• Intrauterine device (IUD)2 
• Intrauterine hormone-releasing system (IUS)2 
• Bilateral tubal occlusion2 
• Vasectomized partner2,3 
• Sexual abstinence4 
 
1  Hormonal contraception may be susceptible to interaction with the IMP, which may reduce the efficacy of the 
contraception method. 
2  Contraception methods that in the context of this guidance are considered to have low user dependency. 
3  Vasectomised partner is a highly effective method of avoiding pregnancy provided that partner is the sole sexual 
partner of the WOCBP trial participant and that the vasectomized partner has received medical assessment of the 
surgical success.  
4  In the context of this guidance, sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with the study treatments.  The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the 
preferred and usual lifestyle of the subject. 
Source:  CTFG 2014. 


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APPENDIX B. PROCEDURES AND SUPPORTIVE CARE GUIDELINES 
FOR SUBJECTS EXHIBITING IMMUNE-RELATED 
ADVERSE EVENTS  
irAE 
Supportive Care 
Pneumonitis 
For Grade 2 (mild to moderate new symptoms): 
• 
Monitor symptoms daily and consider hospitalization.  
• 
Promptly start systemic steroids per institutional standard of care. 
• 
Consider adding prophylactic antibiotics for opportunistic infections in the 
case of prolonged steroid administration. 
• 
Reimaging as clinically indicated. 
• 
If no improvement within 3 to 5 days, additional work-up should be considered 
and prompt treatment with IV methylprednisolone should be started. 
• 
If still no improvement within 3 to 5 days despite IV methylprednisone, 
consider starting immunosuppressive therapy (eg, infliximab), after discussing 
with the medical monitor. 
Caution:  Important to rule out sepsis and refer to infliximab label for general 
guidance before using infliximab.  
• 
Once improving, gradually taper steroids over ≥ 4 weeks and consider 
prophylactic antibiotics, antifungal, or anti-PCP treatment (refer to current 
NCCN Guidelines for treatment of cancer-related infections 
(Category 2B recommendation).  
• 
Consider pulmonary and infectious disease consult.  
For Grade 3 or 4 (severe or new symptoms, new/worsening hypoxia, life 
threatening): 
• 
Promptly initiate empiric IV methylprednisolone or equivalent.  
• 
Carefully monitor subject, and institute medical intervention as appropriate for 
the management of symptoms.  Consider obtaining pulmonary and infectious 
disease consult.  
• 
If no improvement within 3-5 days, additional work-up should be considered 
and prompt treatment with additional immunosuppressive therapy 
(eg, infliximab), after discussing with the medical monitor. 
Caution: Rule out sepsis and refer to infliximab label for general guidance 
before using infliximab.  
• 
Once improving, gradually taper steroids over ≥ 4 weeks and consider 
prophylactic antibiotics, antifungals, and in particular, anti-PCP treatment 
(refer to current NCCN Guidelines for treatment of cancer-related infections 
(Category 2B recommendation).  


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irAE 
Supportive Care 
Diarrhea/Colitis 
Note:  Subjects should be carefully monitored for signs and symptoms of 
enterocolitis (such as diarrhea, abdominal pain, blood or mucus in stool, with or 
without fever) and of bowel perforation (such as peritoneal signs and ileus). 
For Grade 2 (mild to moderate new symptoms): 
• 
Consider symptomatic treatment, including hydration, electrolyte replacement, 
dietary changes (eg, American Dietetic Association colitis diet), and 
loperamide and/or budesonide. 
• 
Promptly start systemic steroids per institutional standard of care. 
• 
If event is not responsive within 3 to 5 days or worsens, gastrointestinal (GI) 
consult should be obtained for consideration of further work-up, and prompt 
treatment with IV methylprednisolone started. 
• 
If still no improvement within 3 to 5 days, consider starting 
immunosuppressives (eg, infliximab) after discussing with the medical 
monitor. 
Caution:  Important to rule out bowel perforation and refer to infliximab label 
for general guidance before using infliximab. 
• 
Consult medical monitor if no resolution to ≤ Grade 1 in 3 to 4 days. 
• 
Once improving, gradually taper steroids over ≥ 4 weeks and consider 
prophylactic antibiotics, antifungals, and anti-PCP treatment (refer to current 
NCCN Guidelines for treatment of cancer-related infections [Category 2B 
recommendation]). 
For Grade 3 or 4 (severe or new symptoms, new/worsening diarrhea, life 
threatening): 
• 
Treatment with systemic corticosteroids should be initiated per institutional 
standard of care. 
• 
Manage symptoms and consider GI consult for further work-up as appropriate. 
• 
If still no improvement within 3 to 5 days, consider starting 
immunosuppressives (eg, infliximab), after discussing with the medical 
monitor. 
Caution:  Ensure GI consult to rule out bowel perforation and refer to 
infliximab label for general guidance before using infliximab. 
• 
Once improving, gradually taper steroids over ≥ 4 weeks and consider 
prophylactic antibiotics, antifungals, and anti-PCP treatment (refer to current 
NCCN Guidelines for treatment of cancer-related infections [Category 2B 
recommendation]). 


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irAE 
Supportive Care 
Hepatitis 
For Grade 2 (mild to moderate new symptoms): 
• 
Observe subject with regular and frequent checking of liver chemistries until 
improving or resolved. 
• 
Rule out non-irAE etiologies. 
• 
If event is persistent (> 3-5 days) or worsens, consider starting systemic 
steroids per institutional standard of care. 
• 
If still no improvement within 3 to 5 days, consider additional work-up and 
prompt treatment with IV methylprednisolone. 
• 
If still no improvement within 3 to 5 days, consider starting 
immunosuppressives (eg, mycophenolate mofetil), after discussing with the 
medical monitor. 
• 
Infliximab should NOT be used. 
• 
Once improving, gradually taper steroids over ≥ 4 weeks and consider 
prophylactic antibiotics, antifungals, and anti-PCP treatment (refer to current 
NCCN Guidelines for treatment of cancer-related infections [Category 2B 
recommendation]). 
For Grade 3 or 4 (severe or new symptoms, new/worsening hepatitis, life 
threatening): 
• 
Promptly initiate empiric IV methylprednisolone or equivalent. 
• 
If still no improvement within 3 to 5 days, consider starting treatment with 
immunosuppressive therapy (eg, mycophenolate mofetil), after discussing with 
the medical monitor. 
• 
Infliximab should NOT be used. 
• 
Consider hepatology consult for additional work-up, as appropriate. 
• 
Once improving, gradually taper steroids over ≥ 4 weeks and consider 
prophylactic antibiotics, antifungals, and anti-PCP treatment (refer to current 
NCCN Guidelines for treatment of cancer-related infections [Category 2B 
recommendation]). 


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irAE 
Supportive Care 
Dermatitis 
Note:  Monitor subjects for signs and symptoms of dermatitis such as rash and 
pruritus.  Unless an alternate etiology has been identified, signs or symptoms of 
dermatitis should be considered immune-mediated.  If there is any bullous 
formation, the medical monitor should be contacted, and study treatment should be 
discontinued. 
For Grade 2 (mild to moderate new symptoms): 
• 
Consider dermatology consult. 
• 
Consider symptomatic treatment per institutional standard of care. 
• 
Consider moderate-strength topical steroid. 
• 
If no improvement of rash/skin lesions occurs within 3 to 5 days or is 
worsening despite symptomatic treatment and/or use of moderate strength 
topical steroid, discuss with medical monitor and promptly start systemic 
steroids. 
For Grade 3 or 4 (severe or new symptoms, new/worsening dermatitis, life 
threatening): 
• 
Consider dermatology consult. 
• 
Promptly initiate empiric IV methylprednisolone or equivalent. 
• 
Carefully monitor subject, and institute medical intervention as appropriate for 
the management of symptoms.   
• 
Consider hospitalization. 
• 
Once improving, gradually taper steroids over ≥ 4 weeks and consider 
prophylactic antibiotics, antifungals, and anti-PCP treatment (refer to current 
NCCN Guidelines for treatment of cancer-related infections [Category 2B 
recommendation]). 
• 
Discuss with medical monitor. 
Renal Failure or 
Nephritis 
Note:  Subjects should be monitored for signs and symptoms that may be related to 
changes in renal function.  Subjects should be thoroughly evaluated to rule out any 
alternative etiology.  Steroids should be considered in the absence of clear 
alternative etiology even for low-grade events (Grade 2) in order to prevent 
potential progression to higher grade event. 
For Grades 2 to 4:  
• 
Carefully monitor subject, and institute medical intervention as appropriate for 
the management of symptoms.  Consider consult with nephrologist, if 
clinically indicated.   
• 
If event is persistent (> 3-5 days) or worsens, promptly start systemic steroids 
per institutional standard of care. 
• 
If event is not responsive within 3-5 days or worsens despite steroids, 
additional work-up should be considered, and prompt treatment with IV 
methylprednisolone started. 
• 
Once improving, gradually taper steroids over ≥ 4 weeks and consider 
prophylactic antibiotics, antifungals, and anti-PCP treatment (refer to current 
NCCN Guidelines for treatment of cancer-related infections [Category 2B 
recommendation]). 


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irAE 
Supportive Care 
Endocrinopathies 
Note:  Subjects should be monitored for clinical signs and symptoms of 
hypophysitis, adrenal insufficiency (including adrenal crisis), and hyper- or 
hypothyroidism.  Subjects may present with fatigue, headache, mental status 
changes, abdominal pain, unusual bowel habits, and hypotension, or nonspecific 
symptoms which may resemble other causes such as brain metastasis or underlying 
disease.  Unless an alternate etiology has been identified, signs or symptoms of 
endocrinopathies should be considered immune-mediated. 
For Grade 2 (mild to moderate new symptoms):  
• 
In hypophysitis, treat with systemic corticosteroids, per institutional standard 
of care.  When symptoms improve to Grade 1 or less, steroid taper should be 
started and continued over no less than 4 weeks.  Replacement of appropriate 
hormones may be required as the steroid dose is tapered. 
Note:  These suggested supportive care measures also apply to Grade 3 
hypophysitis  
• 
In hyperthyroidism, nonselective beta-blockers (eg, propranolol) are suggested 
as initial therapy. 
• 
In hypothyroidism, thyroid hormone replacement therapy, with levothyroxine 
or liothyronine, is indicated per standard of care. 
Note:  Isolated hypothyroidism may be treated with replacement therapy 
without treatment interruption and without corticosteroids. 
• 
Evaluate endocrine function and, as clinically indicated, consider pituitary 
scan. 
• 
For subjects with abnormal endocrine work-up, except for those with isolated 
hypothyroidism, consider short-term, high-dose corticosteroids 
(eg, methylprednisolone or IV equivalent) and initiate appropriate hormone 
replacement therapy. 
• 
For subjects with normal endocrine work-up (labs or MRI), repeat labs/MRI as 
clinically indicated. 
For Grade 3 or 4 (severe or new symptoms, new/worsening endocrinopathies, 
life threatening): 
• 
Hypothyroidism may be treated with replacement therapy without treatment 
interruption and without corticosteroids. 
• 
In hyperthyroidism, treat with an initial dose of IV corticosteroid followed by 
oral corticosteroids.  Consider initiation of systemic corticosteroids at a dose of 
1-2 mg/kg per day of prednisone or equivalent, and initiate appropriate 
hormone replacement therapy.  Once improving, gradually taper 
immunosuppressive steroids over ≥ 4 weeks. 
• 
In hypophysitis, treat with an initial dose of IV corticosteroids followed by oral 
corticosteroids.  When symptoms improve to Grade 1 or less, steroid taper 
should be started and continued over no less than 4 weeks.  Replacement of 
appropriate hormones may be required as the steroid dose is tapered. 
• 
For adrenal crisis, severe dehydration, hypotension, or shock:  immediately 
initiate intravenous corticosteroids with mineralocorticoid activity. 
• 
Consult endocrinologist. 
• 
Consult medical monitor. 


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irAE 
Supportive Care 
Neuropathies 
Note:  Monitor subjects for symptoms of motor or sensory neuropathy such as 
unilateral or bilateral weakness, sensory alterations, or paresthesia. 
For Grade 2 (mild to moderate new symptoms):  
• 
Consider systemic corticosteroids per institutional standard of care in addition 
to appropriate symptomatic treatment. 
• 
If no improvement within 3-5 days, consider additional work-up and consider 
treating with additional immunosuppressive therapy (eg, IV IgG), after 
discussing with the medical monitor. 
For Grade 3 or 4 (severe or new symptoms, new/worsening neuropathies, life 
threatening): 
• 
Consider initiation of systemic corticosteroids (IV administration should be 
strongly considered) for severe neuropathies. 
• 
Institute medical intervention as appropriate for management of severe 
neuropathy. 
• 
If no improvement within 3-5 days despite IV corticosteroids, consider 
additional workup and consider treating with additional immunosuppressants 
(eg, IV IgG) after discussing with the medical monitor. 
• 
Once stable, gradually taper steroids over ≥ 4 weeks. 


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APPENDIX C. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
DOCUMENT HISTORY 
Document 
Date 
Amendment (Version) 1: 
12 JUN 2017 
Amendment (Version) 2: 
22 AUG 2017 
Amendment (Version) 3: 
18 DEC 2017 
Amendment (Version) 4: 
24 OCT 2018 
Amendment (Version) 5: 
22 JAN 2021 
Amendment 5 (22 JAN 2021) 
Overall Rationale for the Amendment: 
The primary purpose of this amendment is to provide guidance for the management of ongoing 
subjects, as enrollment is complete and sufficient data have been collected for primary and 
secondary endpoint analysis. 
1. Synopsis; Section 5.5.1, Withdrawal Criteria; Section 5.5.2, Withdrawal 
Procedures; Section 6, Study Assessments (Table 10:  Schedule of Clinical 
Assessments); Section 6.3, End of Treatment; Section 6.4.1, Safety Follow-Up; 
Section 6.4.2, Disease Status Follow-Up; Section 6.4.3, Survival Follow-Up; 
Section 7.5, Poststudy Anticancer Therapy Status; Section 7.7.1.1.3, Imaging During 
Follow-Up; Section 7.11.2, Data Collection for Survival Follow-Up 
Description of change:  Disease status and survival follow-up data will only be collected 
until the last safety follow-up visit.  Safety follow-up visits will only include AE and 
concomitant medication assessments. 
Rationale for change:  To update the study assessments as enrollment is complete and 
all ongoing subjects have either been on study treatment for more than 15 months or are 
in follow-up after treatment discontinuation (for any of the treatment withdrawal criteria 
outlined in Section 5.5). 
2. Section 10.1.1, Identification of the Coordinating Principal Investigator; 
Section 10.6, Publication Policy; Section 10.7, Study and Site Closure 
Description of change:  Included the process for identification of the coordinating 
principal investigator and for study and site closure.  Clarified the policy for study 
publications. 
Rationale for change:  To update applicable sections as per current protocol template. 
3. Incorporation of administrative changes:  Other minor administrative changes have 
been incorporated throughout the Protocol to correct inadvertent inconsistencies or 
improve the readability and are noted in the redline version of the amendment. 




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• Other relevant sections were updated accordingly and are noted in the redline version 
of the amendment. 
Rationale for change:  A large proportion of patients fail to respond to anti–PD-1 
treatment; there are very limited remaining treatment options available.  Combining an 
anti-GITR and an anti–PD-1 treatment may synergistically restore T-cell activation, 
enhance antitumor immunity, and overcome the resistance of tumors to the PD-1 therapy. 
3. Synopsis; Section 3.1, Subject Inclusion Criteria 
Description of change:  Addition of a note to inclusion criterion 6c that subjects with 
SCCHN enrolled in Stage 2 of the Phase 2 portion of the study should have progressive 
disease during or within 6 months after their platinum-based therapy. 
Rationale for change:  To more closely define the SCCHN population to be enrolled in 
Stage 2 of the Phase 2 portion of the study. 
4. Synopsis; Section 4.3.1, Planned Number of Subjects 
Description of change:  The total number of subjects to be enrolled in the Phase 2 
portion of the study was updated to reflect changes made to the subject population 
(ie, addition of subjects with PD-1 refractory SCCHN to Treatment Group F) in the Phase 
2 portion of the study. 
Rationale for change:  The sample size is guided by the Simon 2-stage design for 
cervical, gastric, SCCHN, and PD-1/L-1 relapsed melanoma tumor types within a given 
doublet or triplet treatment group and Simon 2-stage design with an expansion stage for 
the PD-1 refractory SCCHN cohort in Treatment Group F. 
5. Synopsis; Section 5.2.2, Standard Immune Therapies 
Description of change:  Update in the infusion times for nivolumab and ipilimumab. 
Rationale for change:  Following recent updates to the recommended infusion times for 
nivolumab and ipilimumab in their respective package inserts, the recommended infusion 
times of nivolumab and ipilimumab have been updated in this study to allow for more 
flexibility with respect to nivolumab/ipilimumab infusion times as per the respective 
package inserts or institutional guidelines. 
6. Section 1.5.2.5, Subjects With Melanoma Who Have Relapsed After Prior 
Treatment With an Anti–PD-1 or Anti–PD-L1 Therapy 
Description of change:  Reference to melanoma subjects has been added to this section. 
Rationale for change:  Reference to subjects with melanoma has been made to clarify 
that this section describes the rationale for inclusion of melanoma subjects who have 
relapsed after prior treatment with an anti–PD-1 or anti–PD-L1 therapy. 
7. Section 3.1, Inclusion Criteria; Section 7.10.1, Tumor Biopsies 
Description of change:  Updated the requirements for the amount of previously collected 
formalin-fixed paraffin embedded baseline tumor tissue material. 
Rationale for change:  To allow for more flexibility with respect to the amount of 
available previously collected baseline tumor tissue material required for eligibility. 








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8. Synopsis; Section 4.1, Overall Study Design; Section 5.2, Study Drugs; Section 6, 
Study Assessments; Section 7.10.1.1, Tumor Tissue Collection Requirements 
Description of change:  Section 4.1 was updated to include the following changes; other 
relevant sections were updated accordingly. 
• The Phase 2 subject population was updated to remove endometrial cancer, 
include cervical cancer, and include PD-1 or PD-L1 relapsed melanoma. 
• Language was added to allow for alternate dose administration schedules and/or 
fixed doses of INCAGN01876 comparable to or less than the highest dose levels 
determined to be safe or pharmacologically active in the Phase 2 portion of the 
study. 
• Figure 1 (Overall Study Design) was updated to reflect changes made to the 
subject population and treatment groups. 
• Treatment Group G (run-in with INCAGN01876 × 2 doses followed by 
monotherapy nivolumab) and Treatment Group K (run-in with INCAGN01876 × 
2 doses followed by nivolumab + ipilimumab) were removed from the study.  
Treatment Group E was updated from sequenced INCAGN01876 × 2 doses 
followed by nivolumab and ipilimumab to a run-in with INCAGN01876 × 
2 doses followed by INCAGN01876 concurrent with nivolumab and ipilimumab. 
• A new Treatment Group C2 (INCAGN01876 + ipilimumab) was added to the 
Phase 2 portion of the study. 
Rationale for change:  The rationale for the subject population and fixed dosing are 
described above. 
Removal of Treatment Groups G and K and revision of Treatment Group E to sequenced 
INCAGN01876 × 2 doses followed by concurrent nivolumab and ipilimumab dosing is 
based on emerging clinical and translational data from the Phase 1 portion of the study.  
Data thus far have not shown sufficient clinical responses or meaningful translational 
changes in immune markers for subjects enrolled in Treatment Group B.  However, a 
clinical response and changes in immune markers were observed in Treatment Group A 
(concurrent dosing).  Therefore, treatment groups investigating sequential monotherapy 
dosing schedule will no longer be explored in the Phase 2 portion of the study. 
Treatment Group C (INCAGN01876 + ipilimumab) will be expanded in the Phase 2 
portion of the study (as Treatment Group C2).  This is based on emerging clinical and 
translational data from the Phase 1 portion of the study showing clinical responses and 
meaningful translational changes in immune markers for subjects enrolled in Treatment 
Group C. 




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13. Section 8.1, Adverse Events 
Description of change:  Clarification was provided regarding reporting of AEs related to 
study disease and/or disease progression.  Adverse events related to study disease or 
disease progression should not be reported as an AE/SAE unless it is considered more 
severe than expected for the participant's condition or considered to be treatment-related 
by the investigator.  Additionally, efficacy endpoints as outlined in Section 2.2 will not 
be reported as AE/SAEs, specifically, any event that is related to disease progression of 
the cancer under study. 
Rationale for change:  The original Protocol language was not clear regarding reporting 
of AEs related to study disease or disease progression. 
14. Incorporation of administrative changes:  Other minor administrative typographical 
changes have been incorporated throughout the Protocol and are noted in the redline 
version of the amendment. 
 


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Amendment 2 (22 AUG 2017) 
Overall Rationale for the Amendment: 
The primary purpose of this amendment is to address clinical trial application review comments 
from the Belgian and Spanish regulatory agencies. 
1. Section 3.1, Subject Inclusion Criteria 
Description of change:  In inclusion criterion 9, clarification was provided that men and 
women of childbearing potential must take appropriate precautions to avoid pregnancy 
from screening through the safety follow-up period, or as required in the nivolumab and 
ipilimumab package insert, whichever is longer. 
Rationale for change:  The Protocol only addressed contraceptive measures that should 
be adopted for the investigational product INCAGN01876 but did not include 
contraceptive measures for the combination drugs nivolumab and ipilimumab.  
2. Section 5.4.1, Dose Modifications; Section 7.6, Safety Assessments 
Description of change:  Clarification was added that subject safety management 
guidelines as outlined within the respective package inserts for nivolumab and 
ipilimumab should be followed as appropriate. 
Rationale for change:  To ensure that the approved safety management guidelines for 
nivolumab and ipilimumab are being followed. 
3. Section 6, Study Assessments (Table 10, Schedule of Clinical Assessments); 
Section 7.6.4, Electrocardiograms 
Description of change:  A 12-lead electrocardiogram (ECG) will be collected every 
8 weeks during the treatment period.  Additional 12-lead ECGs may be performed as 
clinically indicated to manage subject safety. 
Rationale for change:  Per the package insert for nivolumab in Europe, continuous 
monitoring for cardiac adverse reactions is recommended when nivolumab is given in 
combination with ipilimumab. 
4. Section 7.6.5.1, Pregnancy Testing 
Description of change:  Clarification was provided regarding when urine pregnancy 
testing would be medically indicated (eg, in case of loss of menstrual cycle or when 
pregnancy is suspected), as well as how country-specific requirements for urine 
pregnancy testing would be communicated to investigational sites. 
Rationale for change:  To clarify when additional urine pregnancy testing would be 
considered medically indicated and how additional urine pregnancy testing requirements 
will be communicated to investigational sites. 
5. Incorporation of administrative changes:  Other minor administrative typographical 
changes have been incorporated throughout the Protocol and are noted in the redline 
version of the amendment. 


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Amendment 1 (12 JUN 2017) 
Overall Rationale for the Amendment: 
The primary purpose of this amendment is to update the sponsor name and address to Incyte 
Biosciences International Sàrl.   
1. Title Page; Document Headers; Section 10.6, Publication Policy  
Description of change:  The name and address of the sponsor were updated from Incyte 
Europe Sàrl to Incyte Biosciences International Sàrl. 
Rationale for change:  The corporate entity Incyte Europe Sàrl will be merged into 
Incyte Biosciences International Sàrl. 
2. Synopsis; Section 2.1.2, Secondary Objectives; Section 2.2.2, Secondary Endpoints; 
Section 9.4.1.2, Secondary Efficacy Analysis 
Description of change:  Added secondary objective and defined endpoint of disease 
control rate. 
Rationale for change:  Disease control rate can be an important measure of therapeutic 
activity. 
3. Synopsis; Section 3.1, Subject Inclusion Criteria; Section 4.1, Overall Study Design; 
Section 7.10.1.1, Tumor Tissue Collection Requirements 
Description of change:  Clarification was added to specify that only subjects with 
mucosal or cutaneous melanoma will be enrolled.  Additionally, alternative tumor types 
not listed may be allowed to enroll with approval of the medical monitor.   
Rationale for change:  As described in Section 1.5.1 of the Protocol, tumor types that 
have demonstrated clinical responses following blockage of immune checkpoint 
inhibitors were included in Part 1 of the study.  As data in subjects treated with immune 
modulators continues to emerge, the list of indications provided in the Protocol may not 
be comprehensive; therefore, tumor types not listed may be allowed following review of 
the medical monitor. 
4. Synopsis; Section 3.2, Subject Exclusion Criteria 
Description of change:  The laboratory exclusion criterion for total bilirubin was 
updated to exclude subjects with total bilirubin ≥ 1.2 × ULN. 
Rationale for change:  As the safety of novel combinations of immune therapies are 
being assessed in this study, only subjects with sufficient liver function should be 
enrolled into this Phase 1/2 study. 
5. Synopsis; Section 4.1, Overall Study Design 
Description of change:  Added language to allow flexibility in prioritizing enrollment to 
specific treatment groups or cohorts. 
Rationale for change:  Allows the sponsor and investigational sites to prioritize more 
promising treatment groups or cohorts (or deprioritize less promising treatment groups or 
cohorts) based on emerging data. 




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11. Section 10.2, Accountability, Handling, and Disposal of Study Drug 
Description of change:  Clarification was provided regarding records required for study 
drugs that are infused.  Bullet referring to self-administered oral study drugs was 
removed. 
Rationale for change:  Changes were applicable based on administration method of 
study drugs. 
12. Incorporation of administrative changes:  Other minor administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


Signature Page for VV-CLIN-000577 v6.0
Signature Page for VV-CLIN-000577 v6.0
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SAP_001.pdf: 
Official Title: 
A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of 
INCAGN01876 in Combination With Immune Therapies in Subjects 
With Advanced or Metastatic Malignancies 
NCT Number: 
NCT03126110 
Document Date: 
Statistical Analysis Plan (Original Version): 05-December-2017 


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INCAGN 1876-201 Statistical Analysis Plan 
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CONFIDENTIAL 
STATISTICAL ANALYSIS PLAN 
 
INCAGN 1876-201 
 
A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy 
of INCAGN01876 in Combination With Immune Therapies in 
Subjects With Advanced or Metastatic Malignancies 
 
 
 
 
 
IND Number: 
 
Sponsor: 
Incyte Biosciences International Sàrl 
Route de la Corniche 1 
1066 Epalinges, Switzerland 
Protocol Version: 
Protocol Amendment 2 dated 22 AUG 2017 
CRF Approval Date: 
02 MAY 2017 
SAP Version: 
Original  
SAP Author:  
, Ph.D. 
, Biostatistics 
Date of Plan: 
05 DEC 2017 
 
 
This study is being conducted in compliance with good clinical practice, 
including the archiving of essential documents. 


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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS ..........................................................................................................7 
1. 
INTRODUCTION ........................................................................................................9 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS.................................9 
2.1. 
Protocol and Case Report Form Version ......................................................................9 
2.2. 
Study Objectives ...........................................................................................................9 
2.2.1. 
Primary Objectives .......................................................................................................9 
2.2.2. 
Secondary Objectives ...................................................................................................9 
 
10 
2.3. 
Study Endpoints ..........................................................................................................10 
2.3.1. 
Primary Endpoints ......................................................................................................10 
2.3.2. 
Secondary Endpoints ..................................................................................................10 
 
11 
3. 
STUDY DESIGN .......................................................................................................12 
3.1. 
Dose Escalation ..........................................................................................................14 
3.2. 
Phase 2 – Dose Expansion ..........................................................................................15 
3.3. 
Control of Type I Error ...............................................................................................16 
3.4. 
Sample Size Considerations .......................................................................................17 
3.4.1. 
Sample Size in Phase 1 ...............................................................................................17 
3.4.2. 
Sample Size in Phase 2 ...............................................................................................17 
3.5. 
Schedule of Assessments ............................................................................................19 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS ..................................20 
4.1. 
Scheduled Study Evaluations and Study Periods .......................................................20 
4.1.1. 
Day 1 ...........................................................................................................................20 
4.1.2. 
Study Day ...................................................................................................................20 
4.1.3. 
Baseline Value ............................................................................................................20 
4.1.4. 
Last Available Value ..................................................................................................20 
4.1.5. 
Handling of Missing and Incomplete Data .................................................................20 
4.1.6. 
Cycle Length and Duration .........................................................................................21 
4.2. 
Variable Definitions ....................................................................................................22 
4.2.1. 
Variables to Be Derived Only If Not Provided on Case Report Form .......................22 
4.2.2. 
Prior and Concomitant Medication .............................................................................22 


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5. 
STATISTICAL METHODOLOGY ...........................................................................23 
5.1. 
General Methodology .................................................................................................23 
5.2. 
Treatment Groups .......................................................................................................23 
5.3. 
Analysis Populations ..................................................................................................25 
5.3.1. 
Full Analysis Set .........................................................................................................25 
5.3.2. 
Response Evaluable Populations ................................................................................27 
5.3.2.1. 
Phase 1 Response Evaluable Population ....................................................................27 
5.3.2.2. 
Phase 2 Response Evaluable Population ....................................................................28 
 
28 
 
28 
 
28 
 
28 
6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES ...............................................................................................................29 
6.1. 
Baseline and Demographics, Physical Characteristics, and Disease History .............29 
6.1.1. 
Demographics .............................................................................................................29 
6.1.2. 
Baseline Disease Characteristics and Disease History ...............................................29 
6.1.3. 
Prior Therapy ..............................................................................................................29 
6.1.4. 
Medical History ..........................................................................................................29 
6.2. 
Disposition of Subjects ...............................................................................................30 
6.3. 
Protocol Deviations and Violations ............................................................................30 
6.4. 
Exposure .....................................................................................................................30 
6.4.1. 
Exposure for INCAGN01876 .....................................................................................30 
6.4.2. 
Exposure for Nivolumab .............................................................................................31 
6.4.3. 
Exposure for Ipilimumab ............................................................................................31 
6.5. 
Prior and Concomitant Medication .............................................................................32 
7. 
EFFICACY .................................................................................................................32 
7.1. 
General Considerations ...............................................................................................32 
7.2. 
Efficacy Hypotheses ...................................................................................................32 
7.3. 
Analysis of the Primary and Secondary Efficacy Parameters ....................................32 
7.3.1. 
Response Criteria ........................................................................................................32 
7.3.2. 
Objective Response Rate and Best Overall Response ................................................32 
7.3.2.1. 
Confirmed ORR and Confirmed BOR by RECIST v1.1 ............................................32 


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7.3.2.2. 
Unconfirmed ORR and Unconfirmed BOR by RECIST v1.1 – Sensitivity 
and Supportive Analyses for Confirmed ORR and Confirmed BOR by 
RECIST v1.1...............................................................................................................35 
7.3.2.3. 
Confirmed ORR and Confirmed BOR by mRECIST v1.1.........................................36 
7.3.2.4. 
Unconfirmed ORR and Unconfirmed BOR by mRECIST v1.1 – Sensitivity 
and Supportive Analyses for Confirmed ORR and Confirmed BOR by 
mRECIST v1.1 ...........................................................................................................37 
7.3.3. 
Duration of Response .................................................................................................37 
7.3.3.1. 
Duration of Response by RECIST v1.1 ......................................................................37 
7.3.3.2. 
Duration of Response by mRECIST v1.1 ...................................................................37 
7.3.4. 
Duration of Disease Control and Disease Control Rate .............................................38 
7.3.5. 
Largest Percentage Reduction in Sum of Diameters of Target Lesions .....................38 
7.3.6. 
Percentage Change in Sum of Diameters of Target Lesions Over Time ....................38 
7.3.7. 
Progression-Free Survival ..........................................................................................38 
7.3.7.1. 
Progression-Free Survival by RECIST v1.1 ...............................................................39 
7.3.7.2. 
Progression-Free Survival by mRECIST v1.1 ............................................................39 
7.3.8. 
Overall Survival ..........................................................................................................40 
 
.40 
 
40 
8. 
SAFETY AND TOLERABILITY ..............................................................................40 
8.1. 
General Considerations ...............................................................................................40 
8.2. 
Adverse Events ...........................................................................................................40 
8.2.1. 
Adverse Event Definitions ..........................................................................................40 
8.2.2. 
Dose-Limiting Toxicities ............................................................................................41 
8.2.3. 
Maximum Tolerated Dose ..........................................................................................41 
8.2.4. 
Adverse Events of Special Interest or Adverse Events of Clinical Interest ...............42 
8.2.4.1. 
Immune-Related Adverse Events ...............................................................................42 
8.2.4.2. 
Infusion-Related Reactions .........................................................................................42 
8.2.5. 
Adverse Event Summaries ..........................................................................................42 
8.3. 
Clinical Laboratory Tests ...........................................................................................44 
8.3.1. 
Laboratory Value Definitions .....................................................................................44 
8.3.2. 
Laboratory Value Summaries .....................................................................................44 
8.4. 
Vital Signs ..................................................................................................................45 
8.5. 
Electrocardiograms .....................................................................................................46 


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9. 
INTERIM ANALYSES ..............................................................................................47 
9.1. 
Overview of Interim Analyses ....................................................................................47 
9.1.1. 
Interim Analyses for Safety ........................................................................................47 
9.1.2. 
Interim Analyses for Futility ......................................................................................47 
9.1.2.1. 
Simon 2-Stage Futility Rules ......................................................................................47 
9.1.2.2. 
Integrated Bayesian Futility Analysis .........................................................................49 
9.2. 
Data Cutoff for Interim Analysis ................................................................................51 
10. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................51 
10.1. 
Changes to Protocol-Defined Analyses ......................................................................51 
10.2. 
Changes to the Statistical Analysis Plan .....................................................................51 
11. 
REFERENCES ...........................................................................................................52 
APPENDIX A. PLANNED TABLES AND FIGURES .............................................................53 
APPENDIX B. TECHNICAL REPORT FOR INTEGRATED BAYESIAN FUTILITY 
ANALYSIS.................................................................................................................64 
 


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LIST OF TABLES 
Table 1: 
INCAGN01876 Dose Levels and Cohorts .................................................................15 
Table 2: 
Planned Simon 2-Stage Designs for Phase 2 ..............................................................16 
Table 3: 
Probability of Dose Escalation by DLT Rate for 3 + 3 + 3 Design ............................17 
Table 4: 
Derivation of Confirmed Best Overall Response .......................................................34 
Table 5: 
RECIST Evaluation Criteria for Overall Response:  Measurable Disease at 
Baseline .......................................................................................................................35 
Table 6: 
Rules for Determining PD Event Status After an Unconfirmed PD Under 
mRECIST v1.1 ...........................................................................................................36 
Table 7: 
Evaluation and Censoring of Progression-Free Survival ............................................39 
Table 8: 
Identification of Records for Postbaseline By-Visit Summaries ................................45 
Table 9: 
Criteria for Clinically Notable Vital Sign Abnormalities ...........................................46 
Table 10: Criteria for Clinically Notable Electrocardiogram Abnormalities .............................46 
Table 11: Probability of Early Termination of Stage 1 for Simon 2-Stage Design of 
SCCHN in Treatment Groups F, G, and H .................................................................48 
Table 12: Bayesian Pooling Strategy by Tumor Type and Sequencing Strategy .......................50 
Table 13: Operating Characteristics for the Integrated Bayesian Futility Analysis 
Under the Global Null Hypothesis .............................................................................51 
Table 14: Statistical Analysis Plan Versions ..............................................................................51 
 
LIST OF FIGURES 
Figure 1: 
Overall Study Design ..................................................................................................13 
Figure 2: 
Power and Type 1 Error for Various Response Rates for 4 Unique Simon 
2-Stage Designs ..........................................................................................................19 
Figure 3: 
Probabilities of Early Termination for Futility at the End of Simon Stage 1 
for All Simon 2-Stage Designs Based on Various Assumed Rates of 
Response to a Given Dose Level ................................................................................49 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
1876 
INCAGN01876 
 
 
AE 
adverse event 
AUC 
area under the concentration-time curve 
AUC(0-∞) 
AUC from time zero (predose) extrapolated to infinite time 
AUC(0-τ) 
AUC from time zero (predose) to time of last observed quantifiable concentration 
within a subject across all treatments 
BOR 
best overall response 
CI 
confidence interval 
Cmin 
minimum observed concentration 
Cmax 
maximum observed concentration 
CR 
complete response 
CRF 
case report form 
CTCAE 
Common Terminology Criteria for Adverse Events 
DCR 
disease control rate 
DLT 
dose-limiting toxicity 
DMC 
Data Monitoring Committee 
DOR 
duration of response 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
FAS 
full analysis set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GEJ 
gastroesophageal junction 
IL 
interleukin 
Ipi 
ipilimumab 
irAE 
immune-related AE 
JTc 
corrected JT interval 
KM 
Kaplan-Meier 
MedDRA 
Medical Dictionary for Regulatory Activities  
mRECIST v1.1 
modified Response Evaluation Criteria in Solid Tumors version 1.1 
MSI 
microsatellite instability 
MTD 
maximum tolerated dose 
NE 
not evaluable 


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Abbreviation 
Term 
Nivo 
nivolumab 
ORR 
objective response rate 
OS 
overall survival 
PAD 
pharmacologically active dose 
PD 
progressive disease 
PD-1 
programmed death-1 
PD-L1 
programmed death ligand-1 
PFS 
progression-free survival 
 
 
PoS 
probability of success 
PR 
partial response 
PT 
preferred term 
Q2W 
every 2 weeks 
QTcF 
QT interval corrected using the Fridericia formula 
QRS 
QRS is the combination of three of the graphical deflections on an ECG.  It is 
usually the most central and most visually obvious part of the tracing.  It 
corresponds to the depolarization of the right and left ventricles of the human heart. 
RECIST v1.1 
Response Evaluation Criteria in Solid Tumors version 1.1 
RP2D 
recommended Phase 2 dose 
RR 
RR is the interval from the beginning of a QRS complex to the beginning of the next 
QRS complex 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SCCHN 
squamous cell carcinoma of the head and neck 
SD 
stable disease 
SMT 
Safety Management Team 
SOC 
system organ class 
T 
time of last observed quantifiable concentration 
TEAE 
treatment-emergent adverse event 
TFLs 
tables, figures, and listings 
WHO 
World Health Organization  


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1. 
INTRODUCTION 
This is a Phase 1/2 open-label, nonrandomized, multicenter study to determine the safety, 
tolerability, and efficacy of INCAGN01876 when given in combination with immune therapies.  
This study will be conducted in 2 phases.  Phase 1 will use a 3 + 3 + 3 design to determine the 
MTD, or PAD, for INCAGN01876 when given in combination with immune therapies in 
subjects with advanced or metastatic tumors.  Phase 2 of the study will further evaluate the 
safety, tolerability, and efficacy of the recommended dose(s) of INCAGN01876 selected in 
Phase 1 when given in combination with immune therapies in subjects with advanced or 
metastatic endometrial cancer, gastric cancer, and SCCHN.  Section 1 of the Protocol provides a 
detailed description of the investigational product, target patient population, rationale for doses 
to be examined, and potential risks and benefits of treatment with INCAGN01876.  
The purpose of this SAP is to provide details of the statistical analyses that have been outlined in 
the Study INCAGN 1876-201 Protocol.  The scope of this plan includes the interim and final 
analyses that are planned and will be executed by the Department of Biostatistics or designee.  
   
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This SAP is based on INCAGN 1876-201 Protocol Amendment 2 dated 22 AUG 2017 and CRFs 
approved 02 MAY 2017.  Unless superseded by an amendment, this SAP will be effective for all 
subsequent Protocol amendments and CRF versions. 
2.2. 
Study Objectives 
2.2.1. 
Primary Objectives 
Phase 1 
• To evaluate the safety, tolerability, and DLTs of INCAGN01876 in combination with 
immune therapies and to define the RP2D(s) of INCAGN01876 when given in 
combination with immune therapies. 
Phase 2 
• To evaluate the efficacy of INCAGN01876 when given in combination with immune 
therapies by assessing ORR per RECIST v1.1. 
2.2.2. 
Secondary Objectives 
Phase 1 and Phase 2 
• To evaluate the efficacy of INCAGN01876 when given in combination with immune 
therapies by assessing ORR, DOR, duration of disease control, and PFS per 
RECIST v1.1 and mRECIST v1.1. 






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3. 
STUDY DESIGN 
This is an open-label, nonrandomized, Phase 1/2 study to determine the safety, tolerability, and 
efficacy of INCAGN01876 when given in combination with immune therapies.  The MTD or 
PAD of INCAGN01876 when given in combination with immune therapies will be determined 
in Phase 1 of the study.  In Phase 1, subjects will receive escalating doses of INCAGN01876 on 
Day 1 of each cycle.  Phases 1 and 2 of the study will utilize 14-day cycles.  The study will be 
conducted in 2 phases: 
• Phase 1 – Dose Escalation will consist of a 3 + 3 + 3 dose escalation to determine 
the MTD or PAD, defined as a dose that provides a maximal biochemical effect or an 
increase in biomarkers of immune activity of INCAGN01876 when given in 
combination with immune therapies.  Phase 1 will begin with 3 doublet treatment 
groups evaluating the MTD or PAD of INCAGN01876 plus nivolumab (Treatment 
Groups A and B) and the MTD or PAD of INCAGN01876 plus ipilimumab 
(Treatment Group C), which will be explored in parallel.  Dose escalation of the 
triplet immune therapy combinations (Treatment Groups D and E) of INCAGN01876 
plus nivolumab plus ipilimumab will begin enrolling once all of the applicable 
doublet combinations have cleared 3 INCAGN01876 dose levels or the MTD or PAD 
of INCAGN01876 has been determined (whichever occurs first).  Alternative dosing 
schedules will be explored in Phase 1, including concurrent dosing (Treatment 
Group A for the doublet combination of INCAGN01876 plus nivolumab and 
Treatment Group D for the triplet combination) and run-in with INCAGN01876 
× 2 doses followed by immune therapy(ies) (Treatment Group B for the doublet 
combination of INCAGN01876 plus nivolumab and Treatment Group E for the triplet 
combination). 
• Phase 2 – Dose Expansion will further evaluate the safety, tolerability, and efficacy 
of the recommended dose(s) of INCAGN01876 selected in Phase 1 when given in 
combination with immune therapies in subjects with advanced or metastatic 
endometrial cancer, gastric cancer, and SCCHN.  Alternative dosing schedules will be 
explored in Phase 2, including concurrent dosing (Treatment Group F for the doublet 
combination of INCAGN01876 plus nivolumab and Treatment Group J for the triplet 
combination), run-in with INCAGN01876 × 2 doses followed by immune 
therapy(ies) (Treatment Group G for the doublet and Treatment Group K for the 
triplet), and run-in with INCAGN01876 × 2 doses followed by concurrent dosing 
with immune therapy(ies) (Treatment Group H for the doublet and Treatment 
Group L for the triplet). 
See Figure 1 for overall study design. 


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Figure 1: 
Overall Study Design 


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3.1. 
Dose Escalation 
In Phase 1 of the study, the MTD is defined as 1 dose level below that at which ≥ one-third of 
subjects in a particular cohort have DLTs.  The PAD is defined as a dose that provides a 
maximal biochemical effect or an increase in biomarkers of immune activity of INCAGN01876 
when given in combination with immune therapies. 
A DLT will be defined as the occurrence of any toxicity, with the exception of events clearly 
associated with the underlying disease, disease progression, a concomitant medication, or 
comorbidity; the list of toxicities that will be designated as DLTs are provided in Table 6 of the 
Protocol. 
In the dose escalation part of the study, a 3 + 3 + 3 design will be used to determine the MTD or 
PAD of INCAGN01876 when given in combination with immune therapies. 
Phase 1 will begin with 3 doublet treatment groups A, B, and C, which will be explored in 
parallel.  Dose escalation of the triplet treatment groups D and E will be explored in parallel and 
will begin enrolling once all of the applicable doublet combinations have cleared 
3 INCAGN01876 dose levels or the MTD or PAD of INCAGN01876 has been determined 
(whichever occurs first).  The starting dose of INCAGN01876 will be 2 dose levels below the 
last dose cohort deemed safe in the doublet combination.  For example, if 3 mg/kg of 
INCAGN01876 is safe in the doublet combinations with both nivolumab and ipilimumab, then 
the starting dose in the triplet will be 0.3 mg/kg.  If the MTD of INCAGN01876 is 1 mg/kg in 
the doublet combinations, then the starting dose of INCAGN01876 for the triplet immune 
therapy combination will be 0.1 mg/kg.  If there are different MTDs of INCAGN01876 with 
nivolumab and ipilimumab, then the starting dose of the triplet will be 2 dose levels below the 
lowest MTD in the doublet. 
Based on safety data from monotherapy (INCAGN 1876-101), a minimum of 3 evaluable 
subjects will be enrolled in each treatment group beginning with INCAGN01876 Dose Cohort 3 
(1.0 mg/kg; starting dose). 
The first 3 evaluable subjects enrolled within an INCAGN01876 dose cohort will be observed 
for the specified DLT observation period before the next dose cohort begins enrollment.  If 
0 DLTs occur in a cohort of 3 evaluable subjects, a new cohort of 3 evaluable subjects will be 
treated at the next higher dose level.  If 1 of 3 evaluable subjects experiences a DLT, that cohort 
will be expanded to 6 evaluable subjects.  If 1 of 6 evaluable subjects experiences a DLT, a new 
cohort of 3 evaluable subjects will be treated at the next higher dose level.  If 2 of 6 evaluable 
subjects experience a DLT, that cohort will be expanded to 9 evaluable subjects.  If ≥ 2 of 3, 3 of 
6, or 3 of 9 evaluable subjects experience DLTs within a cohort, then that dose level will be 
determined to have exceeded the MTD, and the previous dose level will be considered the MTD.  
If only 3 evaluable subjects were treated at the MTD or PAD, then a minimum of 3 additional 
evaluable subjects will be enrolled before this dose is administered in Phase 2 of the study. 
Additional subjects will be enrolled in a dose cohort to achieve the minimum of 3 evaluable 
subjects.  Depending on the treatment group, a subject must receive at least 2 doses of the 
cohort-specified dose of INCAGN01876, 2 doses of nivolumab, and 1 dose of ipilimumab, or 
must have had a DLT during the DLT observation period, to be considered evaluable.  Subjects 
who dropout for reasons other than a DLT (eg, events clearly associated with the underlying 


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disease, disease progression, concomitant medication, or comorbidity), during the DLT 
observation period will result in the subject being nonevaluable and the subject being replaced.  
Dose modifications should not be made during the DLT observation period without discussion 
with the medical monitor.  The doses of INCAGN01876 to be evaluated in each treatment group 
are summarized in Table 1.  
Table 1: 
INCAGN01876 Dose Levels and Cohorts 
Cohort 
Dose of INCAGN01876 
3 (Starting Dose) 
1.0 mg/kga 
4 
3.0 mg/kg 
5 
5.0 mg/kg 
6 
10.0 mg/kg 
a Based on safety data from the monotherapy (INCAGN 1876-101), the starting dose of INCAGN01876 was 
determined to be 1.0 mg/kg. 
3.2. 
Phase 2 – Dose Expansion 
Enrollment in Phase 2 will begin when the MTD or PAD of INCAGN01876 for a given 
treatment group in Phase 1 has been determined.  Phase 2 of the study will further evaluate the 
safety, tolerability, efficacy, 
and pharmacologic activity of the immune therapy 
combinations in subjects with advanced or metastatic endometrial cancer, gastric cancer 
(including stomach, esophageal, and GEJ), and SCCHN.  Additional tumor-specific cohorts may 
be added, by protocol amendment, based on emerging data. 
Biopsy cohorts will be added at specific institutions for each treatment group (F, G, H, J, K, and 
L), where serial mandatory pretreatment and on-treatment biopsies will be collected 
 
  Approximately 5 subjects who have tumor lesions that 
are amenable to percutaneous biopsy will be enrolled in each biopsy cohort.  The biopsy-specific 
cohorts will be limited to subjects with cervical cancer, endometrial cancer, gastric cancer 
(including stomach, esophageal, and GEJ), hepatocellular carcinoma, melanoma (mucosal or 
cutaneous), Merkel cell carcinoma, mesothelioma, MSI-high colorectal cancer, non–small cell 
lung cancer, ovarian cancer, SCCHN, small cell lung cancer, renal cell carcinoma, 
triple-negative breast cancer, and urothelial carcinoma. 
In Phase 2, a Simon 2-stage design will be run for a cohort of endometrial, gastric, and SCCHN 
subjects within a given doublet or triplet drug expansion cohort to allow for early termination of 
a particular cohort at the end of Stage 1 if there are insufficient responses observed.  The design 
parameters for the individual Simon 2-stage designs are determined by historical response rates 
and will result in different sample sizes and different futility rules, depending on the historical 
response rate for the tumor type and treatment combination.  The planned Simon 2-stage designs 
are summarized in Table 2.  The same Simon 2-stage design parameters will be used for 
alternative dosing sequences in the same tumor type and treatment combination.  For example, 
the gastric cohorts in Treatment Groups F, G, and H will all use the same Simon 2-stage 
parameters. 


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Table 2: 
Planned Simon 2-Stage Designs for Phase 2 
Indication 
Treatment 
Groups 
𝒓𝟏 
𝒏𝟏 
𝒓 
𝒏𝟐 
𝒏 
𝒑𝟎 
𝒑𝟏 
SCCHN 
F, G, H 
3 
16 
10 
30 
46 
15% 
35% 
Gastric 
F, G, H 
3 
16 
10 
30 
46 
15% 
35% 
Endometrial 
F, G, H 
4 
17 
14 
34 
51 
20% 
40% 
SCHHN 
J, K, L 
5 
18 
17 
32 
50 
25% 
45% 
Gastric 
J, K, L 
5 
18 
17 
32 
50 
25% 
45% 
Endometrial 
J, K, L 
7 
21 
19 
27 
48 
30% 
50% 
• 𝑟1:  if 𝑟1 or fewer responses are observed during Stage 1, the study cohort is stopped 
early for futility. 
• 𝑛1:  number of subjects initially enrolled in Stage 1. 
• 𝑛2:  number of subjects enrolled in Stage 2. 
• 𝑟:  if 𝑟 or fewer responses are observed by the end of Stage 2, then no further 
investigation of the drug combination is warranted in the selected tumor type and 
dosing schedule. 
• 𝑛:  total number of subjects. 
• 𝑝0:  insufficient response rate. 
• 𝑝1:  target response rate. 
In Phase 2 of the study, toxicities will continue to be monitored.  If the cumulative incidence of 
Grade 3 to 5 INCAGN01876-related AEs occurs in > 40% of subjects in a particular treatment 
group after 6 subjects have been enrolled, then further enrollment in that treatment group will be 
interrupted until the sponsor, investigators, and regulatory authorities (if applicable) determine 
the appropriate course of action (eg, lower the dose of INCAGN01876, change dose frequency, 
etc).  If a treatment group is discontinued due to toxicity, it may be re-initiated at a previously 
tested lower dose level and/or alternate dosing schedule.  All AEs, regardless of the time of 
occurrence on study, may be considered for DLT determination purposes. 
3.3. 
Control of Type I Error 
For the primary efficacy endpoints, the 1-sided Type I error will be controlled at 0.05 for each 
individual cohort expansion.  Note that this level of significance does not account for the 
multiple expansion cohorts.  For other endpoints, CIs will be reported at a 95% confidence level. 
During the Phase 1 portion of the study, telephone conferences will be scheduled by the sponsor 
with study investigators in order to review cohort-specific data and overall safety data, to agree 
on dose escalation, adjudicate individual high-grade AEs as potentially dose-limiting, and guide 
other major study decisions.  An internal DMC will be assembled to monitor safety data and 


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study conduct on a regular and ongoing basis during the Phase 2 portion of the study.  See 
Section 9 for details regarding the interim analyses conducted in this study. 
3.4. 
Sample Size Considerations 
3.4.1. 
Sample Size in Phase 1 
The primary objective in Phase 1 of the study is to determine the MTD or PAD of 
INCAGN01876 when given in combination with immune therapies.  The total number of 
subjects will depend on the number of dose levels tested in each treatment group before the MTD 
or PAD is established.  Approximately 90 (3 subjects per dose level for 6 dose levels in 
5 treatment groups) to 270 (9 subjects per dose level for 6 dose levels in 5 treatment groups) 
evaluable subjects.  Dose escalation will follow the 3 + 3 + 3 design algorithm.  Based on this 
algorithm, a minimum of 3 evaluable subjects will be enrolled in each cohort beginning with 
Cohort 3 (1 mg/kg; starting dose) and a maximum of 9 evaluable subjects will be enrolled in 
each cohort.  The probability of declaring a dose as safe for various DLT rates in the 3 + 3 + 3 is 
summarized in Table 3. 
Table 3: 
Probability of Dose Escalation by DLT Rate for 3 + 3 + 3 Design 
True DLT Rate 
Probability of Declaring Dose Cohort as Safe 
10% 
94.9% 
20% 
78.4% 
30% 
56.1% 
40% 
35.0% 
50% 
18.9% 
60% 
8.8% 
For example, if the true DLT rate is 50% at a given dose level, there is an 18.9% chance that the 
dose would be escalated.  Further, if the true DLT rate is 20%, there is a 78.4% chance that the 
dose would be escalated.  If the MTD is not determined at the highest dose level tested during 
the study, then the MTD is at or above the highest dose level.  The MTD is below the lowest 
dose level of INCAGN01876 if Cohort 1 is not well-tolerated.  The PAD may be used in lieu of 
the MTD and/or prescribed doses may need to be altered in order to determine the MTD. 
3.4.2. 
Sample Size in Phase 2 
Phase 2 will further evaluate the safety, tolerability, preliminary efficacy, 
and pharmacologic 
activity of the recommended dose of INCAGN01876 in combination with immune therapies as 
part of doublet and triplet drug expansion cohorts.  In Phase 2, a Simon 2-stage design will be 
run for each tumor type within a given doublet or triplet drug expansion cohort. 
The sample size for each tumor type within a given doublet or triplet expansion cohort will be 
guided by the Simon 2-stage design (Simon 1989).  As discussed in Section 3.3, the Simon 
2-stage designs conducted for each tumor type within each doublet or triplet expansion cohort 
have design parameters that are determined by historical response rates and will have different 
sample sizes and different futility rules, depending on the historical response rate. 


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In order to determine whether the target response rate (p1) is likely, an initial number of 
evaluable subjects (n1 subjects) treated at the MTD or PAD and schedule of INCAGN01876 
within the corresponding doublet or triplet expansion cohort will be enrolled in a cohort (Stage 
1).  If there are r1 or fewer responses in the cohort, it will be concluded that the true response rate 
is unlikely to be greater than or equal to the target rate, and no more subjects will be enrolled in 
that tumor type in Stage 2.  In the cohorts in which greater than r1 responses are observed among 
the Stage 1 subjects, n2 additional evaluable subjects will be treated in Stage 2 to estimate the 
response rate.  At the end of Stage 2, if ≤ r subjects have responded among the n evaluable 
subjects, the doublet or triplet schedule will be declared nonpromising for that cohort.  In other 
words, after the study is finished, if there is a sufficient number of responses in the 2 stages 
combined, the study doublet or triplet is considered promising; otherwise it is considered 
nonpromising.  The detailed calculations for each tumor type-specific doublet and triplet cohort 
are based on a 1-sided Type I error of 0.05 and power of 85%.  The individual p0 and p1 values 
for the tumor types within doublet or triplet expansion cohorts are listed in Table 2.  Table 2  
shows that there are 4 unique Simon 2-Stage designs:  the Simon 2-stage designs for gastric and 
SCCHN within the INCAGN01876 + nivolumab cohorts use the same assumptions as the Simon 
2-stage designs for gastric and SCCHN within the INCAGN01876 + nivolumab + ipilimumab 
cohorts.  Figure 2 shows the power to reject the null hypothesis under various response rates for 
the 4 unique Simon 2-stage designs, in which each line of the figure represents the power for a 
unique Simon 2-stage design. 


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Figure 2: 
Power and Type 1 Error for Various Response Rates for 4 Unique Simon 
2-Stage Designs 
 
For the biopsy cohorts, if a predictive biomarker with 33% prevalence is associated with 
response, n = 5 subjects provides an 86.5% probability of enrolling at least 1 subject with the 
predictive biomarker in the cohort in question. 
3.5. 
Schedule of Assessments 
Refer to Protocol Amendment 2 dated 22 AUG 2017 for a full description of all study procedures 
and assessment schedules for this study. 


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4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS 
4.1. 
Scheduled Study Evaluations and Study Periods 
4.1.1. 
Day 1 
Day 1 is the date that the first dose of study treatment (INCAGN01876, nivolumab, or 
ipilimumab) is administered to the subjects.  
4.1.2. 
Study Day  
If a visit/reporting date is on or after Day 1, then the study day at the visit/reporting date will be 
calculated as  
Day # = (Visit/Reporting Date – Day 1 date + 1). 
If the visit/reporting date is before Day 1, then the study day at the visit/reporting date will be 
calculated as  
Day # = (Visit/Reporting Date – Day 1 date). 
A study day of -1 indicates 1 day before Day 1. 
4.1.3. 
Baseline Value 
Baseline is the last nonmissing measurement obtained before the first administration of 
INCAGN01876, nivolumab, or ipilimumab, unless otherwise defined. 
When scheduled assessments and unscheduled assessments occur on the same day and time of 
the assessment or time of first dose is not available, use the following convention to determine 
baseline: 
• If both a scheduled and an unscheduled visit are available on the day of the first dose 
and the time is missing, use the scheduled assessment as baseline. 
• If all scheduled assessments are missing on the day of the first dose and an 
unscheduled assessment is available, use the unscheduled assessment as baseline. 
4.1.4. 
Last Available Value 
The last available value is the last nonmissing measurement obtained after starting 
INCAGN01876, nivolumab, or ipilimumab and within 60 days after the last dose of 
INCAGN01876, nivolumab or ipilimumab. 
4.1.5. 
Handling of Missing and Incomplete Data  
In general, values for missing data will not be imputed unless methods for handling missing data 
are specified in this section or relevant sections.  


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Partial disease diagnosis date will be handled as follows:  
• If only the day is missing, then the imputed day will be the first of the month.  
• If both the month and day are missing, then the imputed day and month will be 
01 JAN.  
• No imputation will be done if the date is completely missing.  
Missing or partial date of last dose will be handled as follows:  
• If only the day is missing, then the imputed date of the last dose will be the earlier 
date of the first day of the month or the date that the subject discontinued treatment.  
• Otherwise, the date that the subject discontinued treatment will be used as the date of 
the last dose.  
For relevant efficacy endpoints, partial death date will be imputed as follows:  
• If mmyyyy for the last contact date = mmyyyy for the death date, then the death date 
will be set to the day after the last contact date.  
• If mmyyyy for the last contact date < mmyyyy for the death date, then the death date 
will be set to the first day of the death month.  
• Otherwise, the partial death date will not be imputed.  
4.1.6. 
Cycle Length and Duration 
Cycle 1 Day 1 is the day that the first dose of INCAGN01876, nivolumab, or ipilimumab is 
administered.  One treatment cycle consists of 14 days.  The first cycle of therapy is defined as 
the period beginning with the first dose of INCAGN01876, nivolumab, or ipilimumab and 
ending the earlier of the following 1) 14 calendar days (inclusive later) or 2) permanent 
discontinuation of 1 or more of the following:  INCAGN01876, nivolumab, and ipilimumab.  
Subsequent cycles have Day 1 as the corresponding visit date associated with the corresponding 
cycle.  Note that dosing of ipilimumab is once every 6 weeks. 
In Phase 2, subjects in Treatment Groups F and H will be administered INCAGN01876 at the 
RP2D determined by Treatment Group A along with nivolumab and subjects in Treatment 
Group G will be administered INCAGN01876 at the RP2D determined by Treatment Group B 
along with nivolumab.  Subjects in Treatment Groups J and L will be administered 
INCAGN01876 at the RP2D determined by Treatment Group D along with nivolumab and 
ipilimumab and subjects in Treatment Groups K will be administered INCAGN01876 at the 
RP2D determined by Treatment Group E along with nivolumab and ipilimumab. 
Subjects will continue to receive INCAGN01876, nivolumab, and ipilimumab as defined in the 
protocol as long as the subject is deriving benefit and has not met any of the Protocol-defined 
conditions for treatment withdrawal. 


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4.2. 
Variable Definitions 
4.2.1. 
Variables to Be Derived Only If Not Provided on Case Report Form 
The following variables will only be calculated if not reported on the CRF: 
• Subject age will be calculated as the integer part of the number of years from date of 
birth to the date of signing the informed consent form (ICF), using the following 
formula: 
Age = integer part of (date of informed consent – date of birth + 1) / 365.25 
4.2.2. 
Prior and Concomitant Medication 
Prior medication is defined as any nonstudy medication started before the first dose of 
INCAGN01876, nivolumab, or ipilimumab. 
Concomitant medication is defined as any nonstudy medication that is started accordingly:  
• Before the date of first administration of INCAGN01876, nivolumab, or ipilimumab 
and is ongoing throughout the study or ends on/after the date of first study treatment 
administration. 
• On/after the date of first administration of INCAGN01876, nivolumab, or ipilimumab 
and is ongoing or ends during the course of study treatment. 
A prior medication could also be classified as "both prior and concomitant medication" if the end 
date is on or after first dose of INCAGN01876, nivolumab, or ipilimumab.  In the listing, it will 
be indicated whether a medication is prior-only, concomitant-only, or both prior and concomitant 
medication. 
For the purposes of analysis, all medications will be considered concomitant medications unless 
the medications can unequivocally be defined as not concomitant. 


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5. 
STATISTICAL METHODOLOGY 
5.1. 
General Methodology 
Unless otherwise noted, SAS software (SAS Institute Inc, Cary, NC; Version 9 or later) will be 
used for the generation of all tables, graphs, and statistical analyses.  Descriptive summaries for 
continuous variables will include, but not be limited to, the number of observations, mean, 
standard deviation, median, minimum, and maximum.  Descriptive summaries for categorical 
variables will include the number and percentage of subjects in each category. 
Interim analyses are planned for this study as defined in Section 9. 
5.2. 
Treatment Groups 
This is a Phase 1/2, open-label, nonrandomized, multicenter, dose-escalation study.  In Phase 1, 
because the starting dose of INCAGN01876 is 1.0 mg/kg in Cohort 3, up to 4 doses of 
INCAGN01876 will be tested.  Data will be summarized by treatment group and by dose level. 
Dose escalation of the triplet immune therapy combinations will begin enrolling once all of the 
applicable doublet combinations have cleared 3 INCAGN01876 dose levels (see Table 1) or the 
MTD or PAD of INCAGN01876 has been determined (whichever occurs first).  The starting 
dose of INCAGN01876 will be 2 dose levels below the last dose cohort deemed safe in the 
doublet combination.  The triplet immune therapy combinations will be explored in parallel as 
outlined in Figure 1. 
• Treatment Group A: 
− INCAGN01876 1.0 mg/kg + nivolumab 240 mg 
− INCAGN01876 3.0 mg/kg + nivolumab 240 mg 
− INCAGN01876 5.0 mg/kg + nivolumab 240 mg 
− INCAGN01876 10.0 mg/kg + nivolumab 240 mg 
• Treatment Group B 
− 1.0 mg/kg run-in with INCAGN01876 × 2 doses followed by nivolumab 240 mg 
− 3.0 mg/kg run-in with INCAGN01876 × 2 doses followed by nivolumab 240 mg 
− 5.0 mg/kg run-in with INCAGN01876 × 2 doses followed by nivolumab 240 mg 
− 10.0 mg/kg run-in with INCAGN01876 × 2 doses followed by nivolumab 240 mg  
• Treatment Group C 
− INCAGN01876 1.0 mg/kg + ipilimumab 1 mg/kg 
− INCAGN01876 3.0 mg/kg + ipilimumab 1 mg/kg 
− INCAGN01876 5.0 mg/kg + ipilimumab 1 mg/kg 
− INCAGN01876 10.0 mg/kg + ipilimumab 1 mg/kg 


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• Treatment Group D 
− INCAGN01876 1.0 mg/kg + nivolumab 3 mg/kg + ipilimumab 1 mg/kg 
− INCAGN01876 3.0 mg/kg + nivolumab 3 mg/kg + ipilimumab 1 mg/kg 
− INCAGN01876 5.0 mg/kg + nivolumab 3 mg/kg + ipilimumab 1 mg/kg 
− INCAGN01876 10.0 mg/kg + nivolumab 3 mg/kg + ipilimumab 1 mg/kg 
• Treatment Group E 
− 1.0 mg/kg run-in with INCAGN01876 × 2 doses followed by nivolumab 3 mg/kg 
+ ipilimumab 1 mg/kg 
− 3.0 mg/kg run-in with INCAGN01876 × 2 doses followed by nivolumab 3 mg/kg 
+ ipilimumab 1 mg/kg 
− 5.0 mg/kg run-in with INCAGN01876 × 2 doses followed by nivolumab 3 mg/kg 
+ ipilimumab 1 mg/kg 
− 10.0 mg/kg run-in with INCAGN01876 × 2 doses followed by nivolumab 
3 mg/kg + ipilimumab 1 mg/kg 
In Phase 2, endometrial, gastric, SCCHN subjects and a separate biopsy cohort will be enrolled 
in each treatment group.  Data will be summarized by treatment group and tumor type–specific 
cohort. 
• Treatment Group F:  RP2D from Treatment Group A INCAGN01876 + nivolumab 
240 mg 
− Cohort 1:  Endometrial 
− Cohort 2:  Gastric 
− Cohort 3:  SCCHN 
− Cohort 4:  Biopsy 
• Treatment Group G:  RP2D from Treatment Group B INCAGN01876 run-in Q2W 
× 2 doses followed by nivolumab 240 mg Q2W 
− Cohort 1:  Endometrial 
− Cohort 2:  Gastric 
− Cohort 3:  SCCHN 
− Cohort 4:  Biopsy 
• Treatment Group H:  RP2D from Treatment Group A INCAGN01876 run-in Q2W 
× 2 doses followed by nivolumab 240 mg Q2W + INCAGN01876 Q2W 
− Cohort 1:  Endometrial 
− Cohort 2:  Gastric 


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− Cohort 3:  SCCHN 
− Cohort 4:  Biopsy 
• Treatment Group J:  RP2D from Treatment Group D INCAGN01876 + nivolumab 
3 mg/kg Q2W + ipilimumab 1 mg/kg Q6W 
− Cohort 1:  Endometrial 
− Cohort 2:  Gastric 
− Cohort 3:  SCCHN 
− Cohort 4:  Biopsy 
• Treatment Group K:  RP2D from Treatment Group E INCAGN01876 run-in Q2W 
× 2 doses followed by nivolumab 3 mg/kg Q2W + ipilimumab 1 mg/kg Q6W  
− Cohort 1:  Endometrial 
− Cohort 2:  Gastric 
− Cohort 3:  SCCHN 
− Cohort 4:  Biopsy 
• Treatment Group L:  RP2D from Treatment Group D INCAGN01876 run-in Q2W 
× 2 doses followed by INCAGN01876 Q2W + nivolumab 3 mg/kg Q2W + 
ipilimumab 1 mg/kg Q6W 
− Cohort 1:  Endometrial 
− Cohort 2:  Gastric 
− Cohort 3:  SCCHN 
− Cohort 4:  Biopsy 
5.3. 
Analysis Populations 
5.3.1. 
Full Analysis Set 
The FAS includes all subjects enrolled in the study who received at least 1 dose of 
INCAGN01876, nivolumab, or ipilimumab.  The FAS will be used for the summary of 
demographics, baseline characteristics, subject disposition, safety, study treatment 
administration, and analyses of all efficacy data. 
• Phase 1 FAS Population 
The Phase 1 FAS population includes all subjects in the FAS population who are 
enrolled in the Phase 1 portion of the study and received at least 1 dose of 
INCAGN01876, nivolumab, or ipilimumab. 


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• Phase 1 FAS INCAGN01876 Population 
The Phase 1 FAS population includes all subjects in the FAS population who are 
enrolled in the Phase 1 portion of the study and received at least 1 dose of 
INCAGN01876. 
• Phase 1 FAS Weighted Nivolumab Population 
The Phase 1 FAS weighted nivolumab population includes all subjects in the FAS 
population who are enrolled in the Phase 1 portion of the study and received at least 
1 dose of nivolumab administered in mg/kg.  This includes subjects enrolled into 
Treatment Groups D and E. 
• Phase 1 FAS Fixed Nivolumab Population 
The Phase 1 FAS fixed nivolumab population includes all subjects in the FAS 
population who are enrolled in the Phase 1 portion of the study and received at least 
1 dose of nivolumab administered in mg.  This includes subjects enrolled into 
Treatment Groups A and B. 
• Phase 1 FAS Ipilimumab Population 
The Phase 1 FAS ipilimumab population includes all subjects in the FAS population 
who are enrolled in the Phase 1 portion of the study and received at least 1 dose of 
ipilimumab. 
• Phase 2 FAS Population 
The Phase 2 FAS population includes all subjects in the FAS population enrolled in 
Phase 2 of the study who received at least 1 dose of INCAGN01876, nivolumab, or 
ipilimumab. 
Specific analysis populations to be used for evaluating the Simon 2-stage efficacy 
rules include the following subgroups: 
− Treatment Group F adenocarcinoma of the endometrium 
− Treatment Group F with gastric cancer  
− Treatment Group F with SCCHN cancer  
− Treatment Group G with adenocarcinoma of the endometrium 
− Treatment Group G with gastric cancer  
− Treatment Group G with SCCHN cancer  
− Treatment Group H with adenocarcinoma of the endometrium 
− Treatment Group H with gastric cancer  
− Treatment Group H with SCCHN cancer  
− Treatment Group J with adenocarcinoma of the endometrium 
− Treatment Group J with gastric cancer  
− Treatment Group J with SCCHN cancer  


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− Treatment Group K with adenocarcinoma of the endometrium 
− Treatment Group K with gastric cancer  
− Treatment Group K with SCCHN cancer  
− Treatment Group L with adenocarcinoma of the endometrium 
− Treatment Group L with gastric cancer  
− Treatment Group L with SCCHN cancer  
Table summaries, unless otherwise indicated, will be provided by treatment group 
and tumor type–specific cohort. 
• Phase 2 FAS INCAGN01876 Population 
The Phase 2 FAS population includes all subjects in the FAS population who are 
enrolled in the Phase 2 portion of the study and received at least 1 dose of 
INCAGN01876. 
• Phase 2 FAS Weighted Nivolumab Population 
The Phase 2 FAS weighted nivolumab population includes all subjects in the FAS 
population who are enrolled in the Phase 2 portion of the study and received at least 
1 dose of nivolumab administered in mg/kg.  This includes subjects enrolled into 
Treatment Groups J, K, and L. 
• Phase 2 FAS Fixed Nivolumab Population 
The Phase 2 fixed FAS nivolumab population includes all subjects in the FAS 
population who are enrolled in the Phase 2 portion of the study and received at least 
1 dose of nivolumab administered in mg.  This includes subjects enrolled into 
Treatment Groups F, G, and H. 
• Phase 2 FAS Ipilimumab Population 
The Phase 2 FAS ipilimumab population includes all subjects enrolled in the Phase 2 
portion of the study who received at least 1 dose of ipilimumab. 
5.3.2. 
Response Evaluable Populations 
5.3.2.1. 
Phase 1 Response Evaluable Population 
The Phase 1 response evaluable population includes all subjects enrolled in Phase 1 of the study 
who have received at least 1 dose of INCAGN01876, nivolumab, or ipilimumab; completed a 
baseline scan; and met at least 1 of the following criteria: 
• ≥ 1 postbaseline scan OR 
• The subject has been on the study for a minimum of 64 days of follow-up OR 
• The subject has discontinued from treatment. 




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6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES 
Appendix A provides a list of data displays.  Sample data displays will be provided in a separate 
document. 
6.1. 
Baseline and Demographics, Physical Characteristics, and Disease 
History 
6.1.1. 
Demographics 
The following demographics will be summarized for the Phase 1 FAS population by treatment 
group and dose level and for the Phase 2 FAS population by treatment group and tumor type:  
age, sex, race, ethnicity, and ECOG performance status. 
6.1.2. 
Baseline Disease Characteristics and Disease History 
For each type of tumor, primary tumor histology, time from initial diagnosis in months, stage at 
initial diagnosis, current stage of disease, current site of disease, and tumor markers will be 
summarized for all subjects in the Phase 1 FAS population by treatment group and dose level and 
Phase 2 FAS population by treatment group and tumor type. 
6.1.3. 
Prior Therapy 
Number of prior systemic cancer therapy regimens will be summarized for all subjects in the 
Phase 1 FAS population by treatment group and dose level and Phase 2 FAS population by 
treatment group and tumor type.  Regimen name, component drugs, start and stop date, purpose 
of the regimen, best response, reason for discontinuation, and date of relapse/progression will be 
listed by total number and by number of prior systemic cancer therapies taken for both advanced 
and metastatic disease. 
Number of subjects who received prior radiation will be summarized for the FAS population.  
Radiotherapy type, body site, start and stop date, total dose, and best response will be listed. 
Number of subjects who had prior surgery or surgical procedure for the malignancies under 
study will be summarized for the FAS population.  Date and description of the surgery/procedure 
will be listed. 
Number of subjects with prior immunotherapy and prior anti–PD-1/PD-L1 therapy will be 
summarized for the Phase 1 FAS population by treatment group and dose level and the Phase 2 
FAS population by treatment group and tumor type.  Prior immunotherapy type, start and stop 
date, total dose, and best response will be listed. 
6.1.4. 
Medical History 
Medical history will be summarized according to assigned treatment group by dose level for 
subjects in the Phase 1 FAS population and by tumor type for the Phase 2 FAS population.  This 
summation will include the number and percentage of subjects with significant medical history 
for each body system/organ class as documented on the CRF. 


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6.2. 
Disposition of Subjects 
The number and percentage of subjects who were enrolled, treated, completed the study, 
discontinued study treatment with a primary reason for discontinuation, and discontinued from 
the study with a primary reason for withdrawal will be summarized for the Phase 1 FAS 
population by treatment group and dose level and for the Phase 2 population by treatment group 
and tumor type.  The number of subjects enrolled by site will also be provided by treatment 
group. 
6.3. 
Protocol Deviations and Violations 
Protocol deviations and violations recorded on the CRF will be presented in the subject data 
listings. 
6.4. 
Exposure 
6.4.1. 
Exposure for INCAGN01876 
For subjects in the FAS population, exposure to INCAGN01876 will be summarized 
descriptively as the following: 
• Total number of infusions:  Total number of infusions per subject with a nonzero 
dose of INCAGN01876. 
• Dose administered per cycle (mg/kg):  The actual dose administered in mg/kg per 
cycle. 
• Total dose administered (mg/kg):  The total cumulative, actual dose administered 
(in mg/kg) across cycles for each subject will be determined according to the 
following calculation: 
− For an infusion 𝑖, let 𝐶𝑖 be the concentration (in mg/mL) of INCAGN01876 and 
𝑉𝑖 be the total volume administered (in mL) reported on the INCAGN01876 
dosing CRF; let 𝑊 be the subject's baseline weight (in kg), and 𝑁 be the total 
number of infusions: 
Total dose administered (in mg/kg) = ∑
𝐶𝑖×𝑉𝑖
𝑊
𝑁
𝑖=1
. 
• Average dose of INCAGN01876 (mg/kg):  The average dose (mg/kg) will be the 
total dose administered (in mg/kg) divided by the total number of infusions. 
• Dose administered per cycle (mg):  The actual dose administered in mg per cycle. 
• Total dose administered (mg):  Total cumulative, actual dose administered (in mg) 
across cycles for each subject will be determined according to the following 
calculation: 
− For an infusion 𝑖, let 𝐶𝑖, 𝑉𝑖, and 𝑁 be defined as above: 
Total dose administered (in mg) = ∑
𝐶𝑖× 𝑉𝑖
𝑁
𝑖=1
. 
• Average dose of INCAGN01876 (mg):  The average dose (mg) will be the total dose 
administered (in mg) divided by the total number of infusions. 


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6.4.2. 
Exposure for Nivolumab 
For subjects in the Phase 1 FAS population by treatment group and dose level and the Phase 2 
FAS population by treatment group and tumor type, exposure to nivolumab will be summarized 
descriptively as the following:  
• Total number of infusions:  Number of infusions of nivolumab (mg) for a subject 
will be the number of administered, nonzero infusions of nivolumab (mg) recorded on 
the Nivolumab Dosing CRF. 
• Dose administered per cycle of nivolumab (mg):  The actual dose administered in 
mg per cycle.  Dose administered per cycle of nivolumab (mg) will only be 
summarized for subjects in the Phase 1 FAS Fixed Nivolumab Population and 
Phase 2 FAS Fixed Nivolumab Population. 
• Average dose of nivolumab (mg):  The average dose of nivolumab (mg) will be the 
sum of the doses of nivolumab recorded (mg) on the Nivolumab Dosing CRF divided 
by the number of infusions of nivolumab (mg).  Average dose of nivolumab (mg) will 
only be summarized for subjects in the Phase 1 FAS Fixed Nivolumab Population and 
Phase 2 FAS Fixed Nivolumab Population. 
• Dose administered per cycle of nivolumab (mg/kg):  The actual dose administered 
in mg/kg per cycle.  Dose administered per cycle of nivolumab (mg/kg) will only be 
summarized for subjects in the Phase 1 FAS Weighted Nivolumab Population and 
Phase 2 FAS Weighted Nivolumab Population. 
• Average dose of nivolumab (mg/kg):  The average dose of nivolumab (mg/kg) will 
be the sum of the doses of nivolumab recorded (mg/kg) on the Nivolumab Dosing 
CRF divided by the number of infusions of nivolumab (mg/kg).  Average dose of 
nivolumab (mg/kg) will only be summarized for subjects in the Phase 1 FAS 
Weighted Nivolumab Population and Phase 2 FAS Weighted Nivolumab Population. 
6.4.3. 
Exposure for Ipilimumab 
• Total number of infusions:  Number of doses of ipilimumab for a subject will be the 
number of administered, nonzero infusions of ipilimumab recorded on the 
Ipilimumab Dosing CRF. 
• Dose administered per cycle of ipilimumab (mg/kg):  The actual dose administered 
in mg/kg per cycle. 
• Average dose of ipilimumab (mg/kg):  The average dose of ipilimumab (mg/kg) 
will be the sum of the doses of ipilimumab recorded on the Ipilimumab Dosing CRF 
divided by the number of infusions of ipilimumab. 


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6.5. 
Prior and Concomitant Medication 
Prior medications and concomitant medications will be coded using the WHO Drug Dictionary 
March 2017 version and summarized by WHO drug class and WHO drug term by treatment 
group and dose level in the Phase 1 FAS population and by treatment group and tumor type in 
the Phase 2 FAS population.  Results will be summarized as number and percentage of subjects 
with prior and concomitant medications by preferred term and WHO drug class. 
7. 
EFFICACY 
Sample data displays are provided in a separate document. 
7.1. 
General Considerations 
The primary efficacy endpoint for this study is ORR per RECIST v1.1 assessed in the Phase 2 
Response Evaluable Population.  Secondary efficacy endpoints of this study include ORR, DOR, 
duration of disease control, DCR, and PFS by investigator assessment based on RECIST v1.1 
and mRECIST v1.1 as well as OS assessed at 1 year and 2 years. 
7.2. 
Efficacy Hypotheses 
Each Simon 2-stage design will test the null hypothesis that the true ORR is less than or equal to 
the clinically insignificant response rate 𝑝0 against the alternative hypothesis that the true ORR is 
equal to the target rate of 𝑝1.  For each Simon 2-stage design, the value for 𝑝0 is determined by a 
historical response rate.  The same values for 𝑝0and 𝑝1will be used for alternative dosing 
sequences in the same tumor type and treatment combination.  For example, the gastric cohorts 
in Treatment Groups F, G, and H will all use the same value for 𝑝0 and 𝑝1. 
7.3. 
Analysis of the Primary and Secondary Efficacy Parameters 
7.3.1. 
Response Criteria 
Overall disease status will be categorized using RECIST v1.1 and mRECIST v1.1.  Subjects will 
have their overall response evaluated as CR, PR, SD, PD, or NE at each postbaseline radiological 
assessment based on changes in target lesions, nontarget lesions, and appearance of new lesions.  
7.3.2. 
Objective Response Rate and Best Overall Response 
7.3.2.1. 
Confirmed ORR and Confirmed BOR by RECIST v1.1 
Per RECIST v1.1, in nonrandomized studies where response is the primary endpoint, 
confirmation of PR and CR is required to ensure responses are not the result of measurement 
error.  Therefore, a subject is defined as a confirmed objective responder if the subject has an 
overall response of CR or PR at any postbaseline visit that is confirmed at a subsequent 
timepoint at least 4 weeks later, before the first occurrence of PD.  Confirmed objective 
responders will be assessed based on RECIST v1.1. 


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Confirmed ORR is defined as the proportion of subjects with confirmed overall responses.  
Confirmed ORR will be estimated with 95% CIs.  Confidence intervals will be based on the 
method for Simon 2-stage CIs of response rates outlined in Koyama and Chen (2008). 
Confirmed ORR will be summarized by treatment group and tumor type as primary endpoint for 
the Phase 2 response evaluable population. 
In general, confirmed BOR is the best response recorded postbaseline before and including the 
first PD, in the order of CR, PR, SD, PD and NE, in which CR and PR must be confirmed at a 
subsequent timepoint at least 4 weeks after the CR or PR is observed.  Responses of CR, PR, or 
SD after the first assessment of PD will not be considered.  In the case of SD, measurements 
must meet the SD criteria at least once after the date of first dose at a minimum interval of 
49 (56 – 7) days.  Subjects who fail to meet this criterion will have confirmed BOR of PD if the 
next available assessment indicates PD or NE if there is no additional assessment available. 
Under RECIST v1.1, if radiologic imaging shows CR or PR, a tumor assessment should be 
repeated at a minimum of 4 weeks to confirm the response in order to claim the CR or PR as the 
confirmed BOR.  If there is no second CR or PR tumor assessment, the CR or PR will be 
unconfirmed.  Table 4 lists the scenarios of responses that can occur after an unconfirmed CR or 
PR and provides a rule for determining the confirmed BOR in each scenario.  A sensitivity 
analysis for the ORR, in which BOR is determined using unconfirmed PR and CR, is detailed in 
Section 7.3.2.2.  
For determination of confirmed BOR, confirmatory scans with a response of NE will be 
subsequently followed by another scan at a minimum of 4 weeks.  For example, in the case of PR 
at the first timepoint followed by NE at a subsequent timepoint, if a third scan shows a PR, then 
the confirmed BOR will be PR.  There will be no third confirmatory scans performed for a loss 
of response.  For example, if a response of PR at the first timepoint is followed by a response of 
SD or PD at a subsequent timepoint, the confirmed BOR will be determined using the rules in 
Table 4. 


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Table 4: 
Derivation of Confirmed Best Overall Response 
Overall Response at 
First Timepoint 
Overall Response at 
Subsequent Timepoint 
Confirmed Best Overall 
Response 
CR 
CR 
CR 
CR 
PR 
SD, PD, or PRa 
CR 
SD 
SD provided minimum criteria for 
SD duration met, otherwise, PD 
CR 
PD 
SD provided minimum criteria for 
SD duration met, otherwise, PD 
CR 
NE 
SD provided minimum criteria for 
SD duration met, otherwise NE 
PR 
CR 
PR 
PR 
PR 
PR 
PR 
SD 
SD 
PR 
PD 
SD provided minimum criteria for 
SD duration met, otherwise, PD 
PR 
NE 
SD provided minimum criteria for 
SD duration met, otherwise NE 
NE 
NE 
NE 
a If a CR is truly met at the first timepoint, then any disease seen at a subsequent timepoint, even disease meeting 
PR criteria relative to baseline, makes the disease status PD at that point (since disease must have reappeared after 
CR).  Confirmed BOR would depend on whether the minimum duration for SD was met.  However, sometimes 
CR may be claimed when subsequent scans suggest small lesions were likely still present and in fact the subject 
had a PR, not a CR at the first timepoint.  Under these circumstances, the original CR should be changed to a PR, 
and the confirmed BOR is PR. 
For subjects with measurable disease at baseline, the RECIST v1.1 assessment criteria presented 
in Table 5 can be used to determine the overall disease status at a given timepoint based on the 
target lesion, nontarget lesion, and new lesion assessment. 


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Table 5: 
RECIST Evaluation Criteria for Overall Response:  Measurable Disease at 
Baseline 
Target Lesions 
Nontarget Lesions 
New Lesions 
Overall Response 
CR 
CR 
No 
CR 
CR 
Non-CR/non-PD 
No 
PR 
CR 
NE 
No 
PR 
PR 
Non-PD or NE 
No 
PR 
SD 
Non-PD or NE 
No 
SD 
Not all evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
7.3.2.1.1. Subgroup Analyses for Confirmed Best Overall Response Under RECIST v1.1 
in Phase 2 
Subgroups will be formed based on the following subject characteristics and baseline variables 
for those subjects enrolled in Phase 2 of the study whose data are available. 
• PD-L1 expression within tumor type:  high, negative/low, unknown 
• Number of prior therapies for advanced and metastatic disease within tumor type 
• Subjects with > 1 postbaseline scan within tumor type 
• Tumor-type disease characteristics including the following: 
− Endometrium – MSI status (high, low, stable, unknown) 
− SCCHN – human papilloma virus status (positive vs negative) 
7.3.2.2. 
Unconfirmed ORR and Unconfirmed BOR by RECIST v1.1 – Sensitivity and 
Supportive Analyses for Confirmed ORR and Confirmed BOR by RECIST v1.1 
A sensitivity analysis for the ORR assessed under RECIST v1.1 will be performed using 
unconfirmed CRs and PRs.  The unconfirmed BOR is defined as the best response recorded 
postbaseline prior to and including the first PD, in the order of CR, PR, SD, PD, and NE.  For 
this definition, responses of CR and PR do not need to be confirmed at a subsequent timepoint.  
In the case of SD, measurements must meet the SD criteria at least once after the date of first 
dose at a minimum interval of 49 (56 – 7) days.  Subjects who fail to meet this criterion will have 
BOR of PD if the next available assessment indicates PD or NE if there is no additional 
assessment available. 
Unconfirmed ORR will be summarized by treatment group and tumor type as a sensitivity 
analysis for the primary endpoint ORR for the Phase 2 Response Evaluable Population and as a 
sensitivity analysis for the secondary endpoint ORR for the Phase 1 Response Evaluable 
Population. 


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7.3.2.2.1. Subgroup Analyses for Unconfirmed Best Overall Response by RECIST v1.1 in 
Phase 1 
For the sensitivity analysis for unconfirmed BOR, subgroups will be formed based on the 
following subject characteristics and baseline variables for those subjects enrolled in Phase 1 of 
the study whose data are available. 
• Prior treatment with an anti–PD-1/PD-L1 therapy within tumor type:  Yes/No 
7.3.2.3. 
Confirmed ORR and Confirmed BOR by mRECIST v1.1 
Under mRECIST v1.1, if radiologic imaging shows CR or PR, a tumor assessment should be 
repeated at a minimum of 4 weeks to confirm the response in order to claim the CR or PR as the 
confirmed BOR.  If there is no second CR or PR tumor assessment, the CR or PR will be 
unconfirmed.  Table 4 lists the scenarios that can occur after an unconfirmed CR or PR in and 
provides a rule for determining the confirmed BOR in each scenario.  A sensitivity analysis for 
the ORR assessed under mRECIST v1.1, in which BOR is determined using unconfirmed PR 
and CR, is detailed in Section 7.3.2.4. 
The mRECIST v1.1 instrument was adapted from RECIST v1.1 to include criteria that accounts 
for new lesions that can occur in immuno-oncology subjects before the occurrence of an SD, PR, 
or CR.  Under mRECIST v1.1, if radiologic imaging shows PD, tumor assessment should be 
repeated at a minimum of 4 weeks but not more than 6 weeks later to confirm the progression.  If 
there is no second PD tumor assessment in the 4- to 6-week follow-up time, the PD will be 
defined as unconfirmed.  Table 6 lists the scenarios that can occur after an unconfirmed PD in at 
least 4 weeks and no more than 6 weeks and provides rules for determining whether or not the 
unconfirmed PD will be counted as an event in the corresponding scenario. 
Table 6: 
Rules for Determining PD Event Status After an Unconfirmed PD Under 
mRECIST v1.1 
Event Occurring After Unconfirmed PD in the 
Confirmation Window (4-6 weeks) 
PD Event Status 
Subject had end of study/end of treatment or started 
new anticancer therapy.  
PD will be confirmed as a PD.  
Subject had a confirmed PD.  
PD will be confirmed as a PD.  
Subject had a CR, PR, SD, or NE.  
PD will not be considered as a PD and counted as 
corresponding CR, PR, SD, or NE for the second 
timepoint only.  
Confirmed ORR by mRECIST v1.1 will be summarized by treatment group and tumor type for 
the Phase 2 response evaluable population. 


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7.3.2.4. 
Unconfirmed ORR and Unconfirmed BOR by mRECIST v1.1 – Sensitivity and 
Supportive Analyses for Confirmed ORR and Confirmed BOR by 
mRECIST v1.1  
A sensitivity analysis for the ORR assessed under mRECIST v1.1 will be performed using 
unconfirmed CRs and PRs.  The unconfirmed BOR is defined as the best response recorded 
postbaseline prior to and including the first PD, in the order of CR, PR, SD, PD and NE.  For this 
definition, responses of CR and PR do not need to be confirmed at a subsequent timepoint.  In 
the case of SD, measurements must meet the SD criteria at least once after the date of first dose 
at a minimum interval of 49 (56 – 7) days.  Subjects who fail to meet this criterion will have 
confirmed BOR of PD if the next available assessment indicates PD or NE if there is no 
additional assessment available. 
Unconfirmed ORR as assessed by mRECIST v1.1 will be summarized by treatment group and 
dose level for the Phase 1 response evaluable population and by treatment group and tumor type 
for the Phase 2 response evaluable population. 
7.3.3. 
Duration of Response 
Duration of response will be assessed with RECIST v1.1 and mRECIST v1.1 criteria.  
Censoring of DOR will follow the same algorithm as the censoring of PFS (as described in 
Section 7.3.7).  Kaplan-Meier curves for DOR will be presented by cohort-specific tumor types.  
The KM estimate of median DOR will be presented with its 95% CI.  The 95% CI will be 
calculated using Brookmeyer and Crowley's method (Brookmeyer and Crowley 1982).  A swim 
plot for DOR will be generated under both RECIST v1.1 and mRECIST v1.1 criteria. 
Duration of response as assessed by RECIST v1.1 and mRECIST v1.1 will be summarized by 
treatment group and dose level for the Phase 1 response evaluable population and by treatment 
group and tumor type for the Phase 2 response evaluable population. 
7.3.3.1. 
Duration of Response by RECIST v1.1 
Under RECIST v1.1, for unconfirmed objective responders, DOR is defined as the time from the 
first overall response contributing to an unconfirmed objective response (CR or PR) to the earlier 
of the subject's death from any cause or first assessment of PD. 
7.3.3.2. 
Duration of Response by mRECIST v1.1 
Under mRECIST v1.1, for unconfirmed objective responders, DOR is the time from the first 
unconfirmed overall response contributing to an unconfirmed objective response (CR or PR) to 
the earlier of the subject's death from any cause or first confirmed assessment of PD.  Note that 
the criteria for the assessment of PD in DOR are the same with ORR, which are presented in 
Section 7.3.2.3. 


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7.3.4. 
Duration of Disease Control and Disease Control Rate 
Duration of disease control (CR, PR, and SD) is defined as the time from the first report of SD or 
better until disease progression or death from any cause, if occurring sooner than progression, as 
determined by investigator assessment of radiographic disease per RECIST v1.1 and mRECIST 
v1.1.  Note that the criteria for the assessment of PD in duration of disease control are the same 
with ORR, which are presented in Section 7.3.2.3.  
The duration of disease control will be estimated with 95% CIs overall and by treatment group.  
Confidence intervals will be calculated based on the exact method for binomial distributions.  
Swim plots for duration of disease control will be generated separately for RECIST v1.1 and 
mRECIST v1.1 criteria.  
Disease control rate, defined as the proportion of subjects who have disease control (CR, PR, or 
SD), as per RECIST v1.1 and mRECIST v1.1 will be summarized.  For the determination of 
DCR, response of CR and PR do not need to be confirmed at a subsequent timepoint.  In the case 
of SD, measurements must meet the SD criteria at least after the date of first dose at a minimum 
of 49 (56 – 7) days.  Subjects who fail to meet this criterion will have confirmed BOR of PD if 
the next available assessment indicated PD or NE if there is no additional assessment available.  
Disease control rate will be estimated with 95% CIs. 
Duration of disease control and DCR as assessed per RECIST v1.1 and mRECIST v1.1 will be 
summarized by treatment group and dose level for the Phase 1 response evaluable population and 
by treatment group and tumor type for the Phase 2 response evaluable population. 
7.3.5. 
Largest Percentage Reduction in Sum of Diameters of Target Lesions 
For each subject in the FAS population with target lesions at baseline, target lesion sizes will be 
measured by sum of diameters.  The best percentage change from baseline, defined as the largest 
decrease in target lesion size for each subject, will be summarized descriptively, and a waterfall 
plot of the best percentage change will be generated.  
Per RECIST criteria, target lesions considered "too small to measure" will be assigned a default 
value of 5 mm for purposes of this analysis.  Likewise, target lesions identified as "not present" 
at postbaseline assessments will be assigned 0 mm for this analysis.  In the event a target lesion 
is unaccounted for in a particular postbaseline timepoint (ie, assessment missing or NE), then the 
overall sum of diameters for target lesions will not be evaluable for that postbaseline timepoint. 
7.3.6. 
Percentage Change in Sum of Diameters of Target Lesions Over Time 
For each subject in the FAS population with target lesions at baseline, target lesion sizes will be 
measured by sum of diameters.  The percentage change in sum of diameter of target lesions over 
time will be listed and a spider plot will be generated. 
7.3.7. 
Progression-Free Survival 
Progression-free survival is defined as the length of time between the baseline visit (Day 1) and 
the earlier of death or PD as assessed by RECIST v1.1 and mRECIST v1.1.  Date of death will 
be determined using the Death Report CRF. 


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Censoring for PFS will follow the algorithm outlined in Table 7 which is based on the FDA –
Guidance for Industry:  Clinical Trial Endpoints for the Approval of Cancer Drugs and Biologics 
(FDA 2007). 
Kaplan-Meier curves for PFS will be presented by cohort-specific tumor types.  The KM 
estimate of median PFS will be presented with its 95% CI.  The 95% CI will be calculated using 
the Brookmeyer and Crowley's method (Brookmeyer and Crowley 1982). 
Table 7: 
Evaluation and Censoring of Progression-Free Survival 
Situation 
Outcome 
Date of Progression or Censoring 
No baseline tumor assessments 
Censored 
Date of Day 1  
No valid postbaseline response assessments 
Censored 
Date of Day 1  
Progression documented between scheduled 
response assessments 
Progressed 
Date of first overall response of PD  
No progression 
Censored 
Date of last valid radiologic assessment 
(not NE and not missing)  
Study discontinuation for undocumented 
progression 
Censored 
Date of last valid radiologic assessment 
(not NE and not missing)  
Study discontinuation for toxicity or other 
reason 
Censored 
Date of last valid radiologic assessment 
(not NE and not missing)  
New anticancer treatment started 
Censored 
Date of last valid radiologic assessment 
(not NE and not missing) on/before 
starting a new anticancer treatment. 
(Date of PD assessment if the new 
anticancer treatment started after PD.)  
Death before first progressive response 
assessment 
Progressed 
Date of death  
Death between adequate response assessments 
Progressed 
Date of death  
Death or progression after more than 1 missed 
assessment 
Censored 
Date of last valid radiologic assessment 
(not NE and not missing) before death  
NE = not evaluable. 
7.3.7.1. 
Progression-Free Survival by RECIST v1.1 
Under RECIST v1.1, PFS is defined as the length of time between the baseline visit (Day 1) and 
the earlier of death or first assessment of PD as assessed by RECIST v1.1. 
7.3.7.2. 
Progression-Free Survival by mRECIST v1.1 
Under mRECIST v1.1, PFS is defined as the length of time between the baseline visit (Day 1) 
and the earlier of death or first confirmed assessment of PD (as described in Section 7.3.2.3 
Table 6). 




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Adverse events will be tabulated by MedDRA PT and SOC.  Severity of AEs will be graded 
using the National Cancer Institute CTCAE.  The CTCAE version 4.03 is used for this study.  
The CTCAE reporting guidelines and grading details are available on the Cancer Therapy 
Evaluation Program website. 
The subset of AEs considered by the investigator to be related to INCAGN01876, nivolumab, or 
ipilimumab will be considered to be treatment-related AEs and will be summarized.  If the 
investigator does not specify the relationship of the AE to study treatment, the AE will be 
considered to be treatment-related.  The incidence of AEs and treatment-related AEs will be 
tabulated.  In addition, SAEs will also be tabulated. 
A grading (severity) scale is provided for each AE term.  If the toxicity is not included in the 
CTCAE v4.03 criteria, it will be rated on a scale of 1 to 5 as follows:  1 = mild, 2 = moderate, 
3 = severe, 4 = life threatening, and 5 = death related to AE.  All toxicities will be graded based 
on the worst level reached, not the level they may have reached if they had not been treated.  
When the intensity of an AE changes over time for a reporting period (eg, between visits), each 
change in intensity will be collected as an AE until the event resolves.  Only the worst grade will 
be reported in AE summaries.  Also, the Grade 3 or higher AEs will be reported in a listing. 
Any missing onset date, causality, or severity must be queried for resolution.  Unresolved 
missing causality and severity will be handled according to the following rules: 
• An unresolved missing causality will be considered treatment-related. 
• An unresolved missing severity will be identified as an unknown severity.  
For purposes of analysis, all AEs will be considered TEAEs unless the AE can unequivocally be 
defined as not treatment emergent.   
8.2.2. 
Dose-Limiting Toxicities 
The number of subjects with DLTs and the type of DLT will be listed by dose level and 
treatment group.  An AE for a subject will be identified as a DLT if the event is recorded as a 
protocol-defined DLT on the AE CRF. 
8.2.3. 
Maximum Tolerated Dose 
The MTD, or PAD, is defined as a dose that provides a maximal biochemical effect, or an 
increase in biomarkers of immune activity of INCAGN01876 when given in combination with 
immune therapies.  
• In Phase 1 of the study, the MTD will be defined as 1 dose level below that at which 
≥ one-third of subjects in a particular cohort have DLTs. 
• In Phase 2 of the study, toxicities will continue to be monitored.  If the cumulative 
incidence of Grade 3 or higher related AEs occurs in > 40% of subjects in a particular 
treatment group after 6 subjects have been enrolled, then further enrollment may be 
interrupted until the sponsor, investigators, and regulatory authorities (if applicable) 
determine the appropriate course of action (eg, lower the dose of INCAGN01876, 
change dose frequency).  If a treatment group is discontinued due to toxicity, it may 
be re-initiated at a previously tested lower dose level and/or alternate dosing 
schedule. 


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• All AEs, regardless of the time of occurrence on study, may be considered in DLT 
determination purposes. 
8.2.4. 
Adverse Events of Special Interest or Adverse Events of Clinical Interest 
8.2.4.1. 
Immune-Related Adverse Events 
The number of subjects with irAEs and type of irAE will be listed by treatment group and dose 
level for the Phase 1 FAS population and by treatment group and tumor type in the Phase 2 FAS 
population.  Adverse event terms will be reviewed periodically without respect to treatment 
group by the medical monitor and clinical scientist to determine which AE terms correspond to 
irAEs.  This periodic review may also occur after database lock.  The medical monitor and 
clinical scientist will also review investigator-reported AEs to determine whether they qualify as 
irAEs.  For example, a rash will be counted as an irAE even if the investigator did not report it as 
an irAE. 
8.2.4.1.1. Adverse Events Identified as Inycte MedDRA Queries 
Prospectively defined Incyte MedDRA Queries will be used to conduct analyses to evaluate the 
safety profile.  Incyte MedDRA Queries are queries constructed by Incyte based on MedDRA 
preferred terms identified through review of standardized MedDRA queries for clinically 
relevant terms.  Sets of included terms will be identified and archived before database lock for 
the individual studies.  Incyte MedDRA Queries searches are to be conducted for the following 
TEAEs:  hemorrhage events, dizziness, weight gain, thrombotic events, urinary tract infections, 
herpes zoster infections, tuberculosis, hepatitis B reactivation, and infections other than those 
stated previously.  In addition, these other infections will be analyzed by subcategories of upper 
respiratory tract infections, lower respiratory tract infections, skin and soft tissue infections, 
alimentary tract infections, other viral infections, and miscellaneous infections with each 
tabulated by MedDRA preferred term. 
8.2.4.2. 
Infusion-Related Reactions 
Infusion-related reactions, defined as AEs that are identified as infusion-related reaction by the 
investigator on the infusion-related reaction case report form, will be summarized in a table and 
listing.  The summaries will include the treatment group, dose level, cycle number, study day, 
date of onset of AE, date of the associated infusion, and signs and symptoms of the 
infusion-related reaction. 
8.2.5. 
Adverse Event Summaries 
An overall summary of AEs by treatment group and by tumor type as applicable will include the 
following: 
• Number (%) of subjects reporting any TEAEs 
• Number (%) of subjects reporting any DLTs 
• Number (%) of subjects reporting any SAEs 
• Number (%) of subjects reporting any Grade 3 or 4 TEAEs 


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• Number (%) of subjects reporting any TEAEs related to INCAGN01876 
• Number (%) of subjects reporting any TEAEs related to nivolumab 
• Number (%) of subjects reporting any TEAEs related to ipilimumab 
• Number (%) of subjects who temporarily interrupted INCAGN01876  because of 
TEAEs 
• Number (%) of subjects who temporarily interrupted nivolumab because of TEAEs 
• Number (%) of subjects who temporarily interrupted ipilimumab because of TEAEs 
• Number (%) of subjects who permanently discontinued INCAGN01876 because of 
TEAEs 
• Number (%) of subjects who permanently discontinued nivolumab because of TEAEs 
• Number (%) of subjects who permanently discontinued ipilimumab because of 
TEAEs 
• Number (%) of subjects with INCAGN01876 dose reductions because of TEAEs  
• Number (%) of subjects who had a fatal TEAE 
• Number (%) of subjects who withdrew from study because of a TEAE 
The following summaries will be produced by MedDRA term: 
• Summary of TEAEs by SOC and PT 
• Summary of TEAEs by PT in decreasing order of frequency 
• Summary of TEAEs by SOC, PT, and maximum severity 
• Summary of Grade 3 or higher TEAEs by SOC and PT 
• Summary of INCAGN01876 treatment-related AEs by SOC and PT 
• Summary of nivolumab treatment-related AEs by SOC and PT 
• Summary of ipilimumab treatment-related AEs by SOC and PT 
• Summary of Grade 3 or higher INCAGN01876 treatment-related AEs by SOC and 
PT 
• Summary of Grade 3 or higher nivolumab treatment-related AEs by SOC and PT 
• Summary of Grade 3 or higher ipilimumab treatment-related AEs by SOC and PT 
• Summary of INCAGN01876 treatment-related AEs with a fatal outcome by SOC and 
PT 
• Summary of nivolumab treatment-related AEs with a fatal outcome by SOC and PT 
• Summary of ipilimumab treatment-related AEs with a fatal outcome by SOC and PT 
• Summary of treatment-emergent SAEs by SOC and PT 
• Summary of treatment-emergent SAEs by PT in descending order of frequency 


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• Summary of INCAGN01876 treatment-related SAEs by SOC and PT 
• Summary of nivolumab treatment-related SAEs by SOC and PT 
• Summary of ipilimumab treatment-related SAEs by SOC and PT 
• Summary of treatment-emergent non-SAE by SOC and PT.  
• Summary of TEAEs leading to INCAGN01876 dose reduction by SOC and PT 
• Summary of TEAEs leading to any dose interruption by SOC and PT 
• Summary of TEAEs leading to discontinuation of INCAGN01876 by SOC and PT 
• Summary of treatment-emergent irAEs (investigator identified) by SOC and PT 
• Summary of treatment-emergent irAEs (sponsor identified) by SOC and PT 
• Summary of treatment-emergent irAEs (investigator identified) by SOC, PT, and 
maximum severity 
• Summary of Grade 3 or higher treatment-emergent irAEs (investigator identified) by 
SOC and PT 
• Life table estimate of time to first Grade 3 or higher TEAEs  
• Summary of TEAEs leading to death by SOC and PT 
• Summary of infusion reactions 
8.3. 
Clinical Laboratory Tests 
8.3.1. 
Laboratory Value Definitions 
Laboratory values and change from baseline values will be summarized descriptively by visit.  
Baseline will be determined according to Section 4.1.3.  If there are multiple values that meet the 
criteria for baseline, additional rules may be provided after consultation with the medical monitor 
to delineate which value will be defined as baseline. 
Laboratory test values outside the normal range will be assessed for severity based on CTCAE 
grade or similar criteria where clinical intervention is required for CTCAE grading.  The 
incidence of abnormal laboratory values and shift tables relative to baseline will be tabulated. 
8.3.2. 
Laboratory Value Summaries 
Laboratory values and change from baseline values will be summarized descriptively by visit.  
The baseline value will be determined using the nonmissing values collected before the first 
dose, prioritizing scheduled assessments for baseline identification over unscheduled visits.  The 
last record before administration in the highest priority will be considered the baseline record.  
For baseline laboratory candidates with the same date and time in the same priority category, 
additional rules may be provided after consultation with the medical monitor to delineate which 
value will be defined as baseline. 
All test results and associated normal ranges from local laboratories will be reported in SI units.  
All tests with numeric values will have a unique unit per test.  Any laboratory test results and 


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associated normal ranges from local laboratories will be converted to SI units.  For the limited 
number of cases where the associated normal ranges from a local laboratory cannot be obtained 
despite due diligence, if query is unsuccessful at resolving the issue and analysis is mandatory 
then the clinical scientist and medical monitor can provide a suitable normal range to be used in 
determining CTC grading and flags for above and below normal. 
When there are multiple laboratory nonmissing values for a subject's particular test at a 
scheduled visit, the laboratory value with the smallest laboratory sequence number will be used 
in by-visit summaries (Table 8). 
Table 8: 
Identification of Records for Postbaseline By-Visit Summaries 
Priority 
Laboratory Visit 
Proximity to Visit 
Window 
Tiebreaker 
1 
Scheduled 
In-window 
Use smallest laboratory 
sequence number 
2 
Unscheduled 
In-window 
3 
Scheduled 
Out-of-window 
Numeric laboratory values will be summarized descriptively in SI units, and non-numeric test 
values will be tabulated when necessary.  In addition, line graphs and box-and-whisker plots will 
be provided for hemoglobin, platelet counts, white blood cells, and neutrophils. 
For test results that will be summarized with available normal ranges, the number and percentage 
of subjects with the laboratory values being low (but never high), normal, high (but never low), 
and both low and high will be calculated for each test.  This shift summary will be produced for 
each test for the safety population.  The denominator for the percentage calculation will use the 
number of subjects in the baseline category (ie, low, high, normal, missing) as the denominator 
for the percentage in each of the categories during the treatment period. 
In cases where differentials of hematology parameters are obtained without corresponding 
absolute count data, efforts will be made to investigate if the conversion to an absolute value will 
lead to additional abnormalities.  This will be discussed with the clinical team regarding 
appropriate documentation and action. 
8.4. 
Vital Signs 
Values at each scheduled visit, change, and percentage change from baseline for vital signs, 
including systolic blood pressure, diastolic blood pressure, pulse, respiration rate, and body 
temperature will be summarized descriptively.   
Criteria for clinically notable vital sign abnormalities are defined in Table 9.  The abnormal 
values for subjects exhibiting clinically notable vital sign abnormalities will be listed along with 
their assigned treatment group.  Alert vital signs are defined as an absolute value outside the 
defined range and percentage change > 25%.  The abnormal values for subjects exhibiting alert 
vital sign abnormalities will be listed. 


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Table 9: 
Criteria for Clinically Notable Vital Sign Abnormalities 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
> 155 mmHg 
< 85 mmHg 
Diastolic blood pressure 
> 100 mmHg 
< 40 mmHg 
Pulse 
> 100 bpm 
< 45 bpm 
Temperature 
> 38ºC 
< 35.5ºC 
Respiratory rate 
> 24/min 
< 8/min 
8.5. 
Electrocardiograms 
Twelve-lead ECGs including heart rate, PR, QRS, QT, QTcF, QTcB, JTc, and RR intervals will 
be obtained for each subject at the screening, end of treatment, and safety follow-up visits during 
the study.  Values at each scheduled visit, change, and percentage change from baseline will be 
summarized for each ECG parameter.  Baseline will be determined as the average of all 
nonmissing values before the first administration of INCAGN01876, nivolumab, or ipilimumab. 
Criteria for clinically notable ECG abnormalities are defined in Table 10.  Subjects exhibiting 
clinically notable ECG abnormalities will be listed with study visit and assigned treatment group.  
Abnormal values for subjects with alert ECG values, defined as both the absolute value and the 
percentage change from baseline being outside normal ranges, will be identified and listed. 
Table 10: 
Criteria for Clinically Notable Electrocardiogram Abnormalities 
Parameter  
High Threshold  
Low Threshold  
QTcF 
> 460 msec 
< 295 msec 
PR  
> 220 msec 
< 75 msec 
QRS  
> 120 msec 
< 50 msec 
QT  
> 500 msec 
< 300 msec 
RR  
> 1330 msec 
< 600 msec 
QTcF = Fridericia correction. 


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9. 
INTERIM ANALYSES 
9.1. 
Overview of Interim Analyses 
9.1.1. 
Interim Analyses for Safety 
There will be no planned, formal interim analyses for the Phase 1 dose escalation portion of the 
study.  The review of accrued clinical data will be conducted by Incyte and provided to study 
investigators via teleconferences at the end of Phase 1 of the study.  Based on review of the most 
current safety data, the sponsor (in consultation with the study investigators and using the 
dose-escalation/de-escalation rules) will determine if and at what dose additional subjects should 
be treated in the study. 
A DMC will be charged with evaluating interim safety results.  The DMC will be comprised of 
members who are internal to the sponsor but not members of the study team.  The DMC 
members will include a medical monitor who will serve as the DMC chair and meeting 
facilitator, the head of biostatistics or a designee, the head of regulatory affairs or a designee, and 
the study medical monitor who will be a nonvoting member.  The DMC will meet at least every 
6 months to review the rate of DLTs and irAEs in each treatment group and the overall safety of 
the subjects treated with INCAGN01876, nivolumab, and ipilimumab.  Additional operational 
details of the interim analyses, including TFLs provided to the DMC, will be provided in the 
DMC Charter.  Additional safety analyses may be performed at the discretion of the DMC chair. 
Formal quarterly safety reviews will be conducted by the SMT to review safety data with the 
obligation to hold an SMT meeting on a quarterly basis.  Per the Data Monitoring Charter, the 
DMC is obligated to meet at least every 6 months starting after the first 10 subjects have been 
dosed to review safety data with key tables, listings, and figures for review specified in the Data 
Monitoring Charter.  During Phase 2, the study team will review efficacy and safety data every 
6 months, with the key tables, listings, and figures for review also specified in the Data 
Monitoring Charter. 
9.1.2. 
Interim Analyses for Futility 
9.1.2.1. 
Simon 2-Stage Futility Rules 
An interim analysis of efficacy will be conducted in Phase 2 by applying the Simon 2-stage 
design for each tumor within a given treatment group.  During Stage 1, 𝑛1 evaluable subjects 
treated at the recommended dose and schedule will be enrolled, and if 𝑟1 or fewer responses 
(Table 2) are observed by the Week 16 assessment, then the cohort will be discontinued.  To be 
counted as evaluable for the calculation in Stage 1, subjects must have discontinued from the 
study, reached the Week 16 assessment, or had at least 2 scans.  As discussed in Section 3.2, the 
Simon 2-stage designs conducted for each tumor type within each treatment group have design 
parameters that are determined by historical response rates and will have different sample sizes 
and futility results depending on the historical response rate. 
As an example, the probability of early termination for Stage 1 in the SCCHN tumor cohort for 
the doublet combination of INCAGN01876 and nivolumab in Treatment Groups F, G, and H is 


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summarized in Table 11.  If at least 4 responses (CR or PR) are observed in the first evaluable 
16 subjects, then 30 additional evaluable subjects will be enrolled in this cohort for Stage 2. 
Per mRECIST v1.1, the tumor response should be confirmed by a repeat radiographic 
assessment not less than 4 weeks from the date that the first response was documented.  Disease 
progression will be confirmed by a second tumor assessment in at least 4 weeks and no later than 
6 weeks after the first scan indicating PD in clinically stable subjects.  The first tumor 
assessment is conducted in the eighth week.  If a CR or PR occurs after an unconfirmed PD in at 
least 4 weeks but no more than 6 weeks, then the tumor assessment will be counted as a 
corresponding CR or PR (Section 7.3.2.3). 
Table 11: 
Probability of Early Termination of Stage 1 for Simon 2-Stage Design of 
SCCHN in Treatment Groups F, G, and H 
True Response Rate 
Probability of Early Termination at Stage 1 
15% 
79.0% 
20% 
59.8% 
25% 
40.5% 
30% 
24.6% 
35% 
13.4% 
Table 11 provides the probabilities of early termination at the end of Simon Stage 1 for various 
response rates with regard to the efficacy analysis of the primary endpoint for the 4 unique 
Simon 2-stage designs given in Table 2.  Each line in Figure 3 represents the probability of early 
termination for a unique Simon 2-stage design. 


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Figure 3: 
Probabilities of Early Termination for Futility at the End of Simon Stage 1 
for All Simon 2-Stage Designs Based on Various Assumed Rates of Response 
to a Given Dose Level 
 
9.1.2.2. 
Integrated Bayesian Futility Analysis 
In Phase 2, individual cohorts will be closed for futility depending on the results of an integrated 
Bayesian analysis in which the pooling model requires a priori specification of 2 parameters:  the 
probability of correlation among the cohorts 𝜆 and the common probability of activity in the 
cohorts 𝛾.  The integrated Bayesian analysis will be performed each time a subject with 
endometrial, gastric, or head and neck cancer enters screening.  Data will be pooled from cohorts 
with a common dose sequencing strategy and from cohorts with a common tumor type, with 𝜆 
and 𝛾 specified separately for pooling within the 2 strategies.  The pooled model will produce a 
posterior PoS calculation for each cohort based on pooling within dose sequencing strategy, 
denoted by PoS1, and pooling within tumor type, denoted by PoS2.  PoS is defined as the 
probability that the ORR for the cohort is greater than or equal to the target response rate, 𝑝1, 
from the Simon 2-stage design for the cohort.  The PoS calculations are adapted from Simon et al 
(2016). 


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The futility rule will stop enrollment in a tumor-sequence pair (𝑖, 𝑗) if both 𝑃𝑃𝑃1𝑖𝑖 or 𝑃𝑃𝑃2𝑖𝑖 are 
< 20% with the possibility to re-open after more data has accrued and subsequent posterior PoS 
values are ≥ 20% for the tumor-sequence pair. 
For the futility analyses, we specify λ = 0.4 and γ=0.4 for pooling within the tumor types and 
λ = 0.4 and γ = 0.4 for pooling within the sequencing strategies.  In other words, a priori, the 
correlation between cohorts within the same tumor type and same dose sequencing strategy is 
assumed to be 40%, and all cohorts within the same tumor type and same dose sequencing 
strategy are assumed to have a 40% probability of activity. 
Further details regarding the Bayesian methodology can be found in Simon et al (2016) and in 
the technical report in Appendix B. 
Table 12 shows the dose sequencing strategy and tumor-type specific strategy for each of the 
18 cohorts used for pooling in the integrated Bayesian analysis.  Each cell in the table contains a 
number 1 to 3 representing the dose sequencing strategy and a number 4 to 9 representing the 
tumor type and treatment information.  For pooling within dose sequencing strategy, all cohorts 
with a common dose sequencing number will be pooled.  For pooling within the tumor types, all 
cohorts with a common tumor type number will be pooled.  For example, for pooling within the 
concurrent dosing sequence, all cohorts with representative cells in the table containing a 1 will 
be pooled.  For pooling within the tumor type strategy of gastric within INCAGN01876 + 
nivolumab, all cohorts with representative cells in the table containing a 5 will be pooled. 
Table 12: 
Bayesian Pooling Strategy by Tumor Type and Sequencing Strategy 
Dosing Schedule 
Tumor Types Within Treatment Group 
Endometrial 
Gastric 
SCCHN 
Treatment Group F 
1, 4 
1, 5 
1, 6 
Treatment Group G 
2, 4 
2, 5 
2, 6 
Treatment Group H 
3, 4 
3, 5 
3, 6 
Treatment Group J 
1, 7 
1, 8 
1, 9 
Treatment Group K 
2, 7 
2, 8 
2, 9 
Treatment Group L 
3, 7 
3, 8 
3, 9 
1 = Concurrent dosing 
2 = Run-in only dosing 
3 = Run-in + concurrent dosing 
4 = Endometrial within 1876 + Nivo 
5 = Gastric within 1876 + Nivo 
6 = SCCHN within 1876 + Nivo 
7 = Endometrial within 1876 + Nivo + Ipi 
8 = Gastric within 1876 + Nivo + Ipi 
9 = SCCHN within 1876 + Nivo + Ipi 
Table 13 provides the operating characteristics for 1000 simulated clinical trials under the global 
null hypothesis, under which none of the 18 cohorts are active.  The table summarizes the 
expected sample size, expected number of false rejections, and the probability of at least 1 false 
positive result (family wise error rate) for the integrated Bayesian analysis.  For comparison 
purposes, the table summarizes the expected sample size, and expected number false rejections 


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for 18 separate Simon 2-stage designs in which the cohorts are stopped for futility according to 
only the Simon 2-stage rules.  In the integrated Bayesian analysis, a cohort can be stopped for 
futility if either PoS1 or PoS2 is not ≥ 20% or because the cohort does not meet the response rate 
requirement of the Simon 2-stage rule at Stage 1.  From the table, under the global null 
hypothesis and certain enrollment assumptions, the integrated Bayesian analysis will result in 
22% fewer subjects on average. 
Table 13: 
Operating Characteristics for the Integrated Bayesian Futility Analysis 
Under the Global Null Hypothesis 
Integrated Bayesian Analysis 
18 Simon 2-Stage Designs 
Expected 
Sample Size 
Probability of at 
Least 1 False Positive 
Expected Number 
of False Rejections 
Expected 
Sample Size 
Expected Number of 
False Rejections 
355.2 
0.0876 
0.104 
457.2 
0.9 
9.2. 
Data Cutoff for Interim Analysis 
As discussed in Section 9.1.1, the DMC will meet every 6 months to review safety analyses.  All 
efficacy and safety analyses will use a clinical data cutoff of 3 weeks before execution of the 
planned safety or interim analysis.  This period will help ensure accuracy of the interim data by 
providing the sponsor time to perform data review, issue queries regarding data quality issues to 
sites, and to resolve such queries. 
As per Section 9.1.2.2, the IRT system will use the number of responses and number of 
evaluable subjects in each cohort to perform the pooled PoS1 and PoS2 calculations for futility 
whenever a subject with endometrial, gastric, or head and neck cancer enters screening.  To 
perform quality control checks of the futility analysis within the IRT system, the sponsor will 
review the disease response data within the IRT system for consistency with the clinical database 
and request changes to resolve discrepancies.  There will be periodic data extracts to identify 
discrepancies between the IRT system and the clinical database. 
10. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN 
All versions of the SAP are listed in Table 14. 
Table 14: 
Statistical Analysis Plan Versions 
SAP Version 
Date 
Original 
05 DEC 2017 
10.1. 
Changes to Protocol-Defined Analyses 
Not applicable. 
10.2. 
Changes to the Statistical Analysis Plan 
Not applicable. 


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11. 
REFERENCES 
Brookmeyer R, Crowley J. A confidence interval for the median survival time. Biometrics 
1982;38:29-41. 
Food and Drug Administration. Guidance for Industry: Clinical Trial Endpoints for the Approval 
of Cancer Drugs and Biologics. 2007. 
http://www.fda.gov/downloads/Drugs/.../Guidances/ucm071590.pdf. Accessed January 4, 2016. 
Koyama T, Chen H. Proper inference from Simon's two-stage designs. Stat Med 
2008;27:3145-154. 
Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials 1989;10:1-10. 
Simon R, Geyer S, Subramanian J, Roychowdhury S. The Bayesian basket design for genomic 
variant-driven phase II trials. Semin Oncol 2016;43:13-18. 


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APPENDIX A. PLANNED TABLES AND FIGURES 
This appendix provides a list of the planned tables and figures for the Clinical Study Report.  
Standard tables will follow the conventions in the Standard Safety Tables initial version.  Shells 
are provided for nonstandard tables in a separate document.  In-text tables are identical in 
structure and content as appendix tables, but follow a Rich Text Format. 
The list of tables, figures, and the shells are to be used as guideline.  Modifications of the list or 
shells that do not otherwise affect the nature of the analysis will not warrant an amendment to the 
SAP. 
Tables 
Table No. 
Title 
Population 
Standard 
In-Text 
1.1 Baseline and Demographic Characteristics 
1.1 
Disposition 
1.1.1.1 
Analysis Populations 
Phase 1 FAS 
Population 
X 
X 
1.1.1.2 
Analysis Populations 
Phase 2 FAS 
Population 
X 
X 
1.1.2.1 
Summary of Subject Disposition 
Phase 1 FAS 
Population 
X 
X 
1.1.2.2 
Summary of Subject Disposition 
Phase 2 FAS 
Population 
X 
X 
1.1.2.3 
Summary of Subject Disposition 
FAS Population 
X 
 
1.1.3.1 
Summary of Number of Subjects Enrolled by Country 
and Site 
Phase 1 FAS 
Population 
X 
 
1.1.3.2 
Summary of Number of Subjects Enrolled by Country 
and Site 
Phase 2 FAS 
Population 
X 
 
1.2 Demography 
1.2.1 
Summary of Demographics  
Phase 1 FAS 
Population 
X 
X 
1.2.2 
Summary of Demographics - by Tumor Type 
Phase 2 FAS 
Population 
X 
X 
1.3 Baseline Characteristics 
1.3.1.1 
Summary of Baseline Disease Characteristics and 
Disease History for Phase 1 Solid Tumor Types 
Phase 1 FAS 
Population 
 
 
1.3.2.1 
Summary of Baseline Disease Characteristics and 
Disease History for Phase 2 Solid Tumor Types 
Phase 2 Biopsy 
FAS Population 
 
 
1.3.2.2 
Summary of Baseline Disease Characteristics and 
Disease History  
Phase 2 
Endometrium FAS 
Population 
 
 
1.3.2.3 
Summary of Baseline Disease Characteristics and 
Disease History  
Phase 2 Gastric 
FAS Population 
 
 
1.3.2.4 
Summary of Baseline Disease Characteristics and 
Disease History  
Phase 2 SCCHN 
FAS Population 
 
 


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Table No. 
Title 
Population 
Standard 
In-Text 
1.4 Prior Medication and Concomitant Medication 
1.4.1.1 
Summary of Prior Systemic Therapy  
Phase 1 FAS 
Population 
 
 
1.4.1.2 
Summary of Prior Systemic Therapy - by Tumor Type 
Phase 2 FAS 
Population 
 
 
1.4.2.1 
Summary of Prior Medications 
Phase 1 FAS 
Population 
 
 
1.4.2.2 
Summary of Prior Medications - by Tumor Type 
Phase 2 FAS 
Population 
 
 
1.4.3.1 
Summary of Concomitant Medications 
Phase 1 FAS 
Population 
X 
 
1.4.3.2 
Summary of Concomitant Medications - by Tumor 
Type 
Phase 2 FAS 
Population 
X 
 
1.5 Others 
1.5.1 
Summary of General Medical History 
Phase 1 FAS 
Population 
X 
 
1.5.2 
Summary of General Medical History - by Tumor 
Type 
Phase 2 FAS 
Population 
X 
 
1.5.3 
Summary of Protocol Deviations 
FAS Population 
 
 
2 Efficacy 
2.1.1.1 
Summary of Confirmed Best Response, Duration of 
Response, and Duration of Disease Control Under 
RECIST v1.1 - by Treatment Group and Tumor Type 
Phase 2 Response 
Evaluable 
Population 
 
X 
2.1.1.2 
Summary of Unconfirmed Best Response Under 
RECIST v1.1 - by Treatment Group and Tumor Type 
Phase 2 Response 
Population 
 
X 
2.2.1 
Summary of Unconfirmed Best Response, Duration of 
Response, and Duration of Disease Control Under 
RECIST v1.1 - by Treatment Group and Dose 
Phase 1 Response 
Evaluable 
Population 
 
X 
2.2.2 
Summary of Unconfirmed Best Response, Duration of 
Response, and Duration of Disease Control Under 
mRECIST v1.1 - by Treatment Group and Dose 
Phase 1 Response 
Evaluable 
Population 
 
X 
2.2.3.1 
Summary of Confirmed Best Response, Duration of 
Response, and Duration of Disease Control Under 
mRECIST v1.1 - by Treatment Group and Tumor Type 
Phase 2 Response 
Evaluable 
Population 
 
X 
2.2.3.2 
Summary of Unconfirmed Best Response Under 
mRECIST v1.1 - by Treatment Group and Tumor Type 
Phase 2 Response 
Evaluable 
Population 
 
X 
2.4.1 
Summary of Progression-Free Survival Under 
RECIST v1.1  
Phase 1 FAS 
Population 
 
X 
2.4.2 
Summary of Progression-Free Survival Under 
RECIST v1.1 - by Tumor Type 
Phase 2 FAS 
Population 
 
X 
2.5.1 
Summary of Progression-Free Survival Under 
mRECIST v1.1  
Phase 1 FAS 
Population 
 
X 
2.5.2 
Summary of Progression-Free Survival Under 
mRECIST v1.1 - by Tumor Type 
Phase 2 FAS 
Population 
 
X 
2.6.1 
Summary of Overall Survival  
Phase 1 FAS 
Population 
 
X 
2.6.2 
Summary of Overall Survival - by Tumor Type 
Phase 2 FAS 
Population 
 
X 


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Table No. 
Title 
Population 
Standard 
In-Text 
Safety 
3.1 Dose Exposure 
3.1.1.1 
Summary of Drug Exposure to INCAGN01876 - by 
Treatment Group and Dose 
Phase 1 FAS 
INCAGN01876 
Population 
 
X 
3.1.1.2 
Summary of Drug Exposure to INCAGN01876 - by 
Treatment Group and Tumor Type 
Phase 2 FAS 
INCAGN01876 
Population 
 
X 
3.1.2.1 
Summary of Drug Exposure to Nivolumab - by 
Treatment Group and Dose 
Phase 1 FAS Fixed 
Nivolumab 
Population 
 
X 
3.1.2.2 
Summary of Drug Exposure to Nivolumab - by 
Treatment Group and Dose 
Phase 1 FAS 
Weighted 
Nivolumab 
Population 
 
X 
3.1.2.3 
Summary of Drug Exposure to Nivolumab - by 
Treatment Group and Tumor Type 
Phase 2 FAS Fixed 
Nivolumab 
Population 
 
X 
3.1.2.4 
Summary of Drug Exposure to Nivolumab - by 
Treatment Group and Tumor Type 
Phase 2 FAS 
Weighted 
Nivolumab 
Population 
 
X 
3.1.3.1 
Summary of Drug Exposure to Ipilimumab - by 
Treatment Group and Dose 
Phase 1 FAS 
Ipilimumab 
Population 
 
X 
3.1.3.2 
Summary of Drug Exposure to Ipilimumab - by 
Treatment Group and Tumor Type 
Phase 2 FAS 
Ipilimumab 
Population 
 
X 
3.1.4.1 
Summary of Drug Exposure to INCAGN01876 by 
Visit - by Treatment Group and Dose 
Phase 1 FAS 
INCAGN01876 
Population 
 
 
3.1.4.2 
Summary of Drug Exposure to INCAGN01876 by 
Visit - by Treatment Group and Tumor Type 
Phase 2 FAS 
INCAGN01876 
Population 
 
 
3.1.5.1 
Summary of Drug Exposure to Nivolumab by Visit - 
by Treatment Group and Dose 
Phase 1 FAS Fixed 
Nivolumab 
Population 
 
 
3.1.5.2 
Summary of Drug Exposure to Nivolumab by Visit - 
by Treatment Group and Dose 
Phase 1 FAS 
Weighted 
Nivolumab 
Population 
 
 
3.1.5.3 
Summary of Drug Exposure to Nivolumab by Visit - 
by Treatment Group and Tumor Type 
Phase 2 FAS Fixed 
Nivolumab 
Population 
 
 


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Table No. 
Title 
Population 
Standard 
In-Text 
3.1.5.4 
Summary of Drug Exposure to Nivolumab by Visit - 
by Treatment Group and Tumor Type 
Phase 2 FAS 
Weighted 
Nivolumab 
Population 
 
 
3.1.6.1 
Summary of Drug Exposure to Ipilimumab by Visit - 
by Treatment Group and Dose 
Phase 1 FAS 
Ipilimumab 
Population 
 
 
3.1.6.2 
Summary of Drug Exposure to Ipilimumab by Visit - 
by Treatment Group and Tumor Type 
Phase 2 FAS 
Ipilimumab 
Population 
 
 
3.2 Adverse Events 
3.2.1.1 
Overall Summary of Treatment-Emergent Adverse 
Events - by Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
X 
3.2.1.2 
Overall Summary of Treatment-Emergent Adverse 
Events - by Treatment Group and Tumor Type 
Phase 2 FAS 
Population 
X 
X 
3.2.2.1 
Summary of Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term - by 
Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
 
3.2.2.2 
Summary of Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term - by 
Treatment Group and Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.2.3.1 
Summary of Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of 
Frequency - by Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
X 
3.2.3.2 
Summary of Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of 
Frequency - by Treatment Group and Tumor Type 
Phase 2 FAS 
Population 
X 
X 
3.2.4.1 
Summary of Treatment-Emergent Adverse Events by 
MedDRA System Organ Class, Preferred Term, and 
Maximum Severity - by Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
 
3.2.4.2 
Summary of Treatment-Emergent Adverse Events by 
MedDRA System Organ Class, Preferred Term, and 
Maximum Severity - by Treatment Group and Tumor 
Type 
Phase 2 FAS 
Population 
X 
 
3.2.5.1 
Summary of Grade 3 or Higher Treatment-Emergent 
Adverse Events by MedDRA System Organ Class and 
Preferred Term - by Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
X 
3.2.5.2 
Summary of Grade 3 or Higher Treatment-Emergent 
Adverse Events by MedDRA System Organ Class and 
Preferred Term - by Treatment Group and Tumor Type 
Phase 2 FAS 
Population 
 
X 
X 
3.2.6.1 
Summary of Any INCAGN01876 Treatment-Related 
Adverse Events by MedDRA System Organ Class and 
Preferred Term - by Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
X 
3.2.6.2 
Summary of Any INCAGN01876 Treatment-Related 
Adverse Events by MedDRA System Organ Class and 
Preferred Term - by Treatment Group and Tumor Type 
Phase 2 FAS 
Population 
X 
X 
3.2.6.3 
Summary of Any Nivolumab Treatment-Related 
Adverse Events by MedDRA System Organ Class and 
Preferred Term - by Treatment Group and Dose 
Phase 1 FAS 
Nivolumab 
Population 
X 
X 


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Table No. 
Title 
Population 
Standard 
In-Text 
3.2.6.4 
Summary of Any Nivolumab Treatment-Related 
Adverse Events by MedDRA System Organ Class and 
Preferred Term - by Treatment Group and Tumor Type 
Phase 2 FAS 
Nivolumab 
Population 
X 
X 
3.2.6.5 
Summary of Any Ipilimumab Treatment-Related 
Adverse Events by MedDRA System Organ Class and 
Preferred Term - by Treatment Group and Dose 
Phase 1 FAS 
Ipilimumab 
Population 
X 
X 
3.2.6.6 
Summary of Any Ipilimumab Treatment-Related 
Adverse Events by MedDRA System Organ Class and 
Preferred Term - by Treatment Group and Tumor Type 
Phase 2 FAS 
Ipilimumab 
Population 
X 
X 
3.2.7.1 
Summary of Any Grade 3 or Higher INCAGN01876 
Treatment-Related Adverse Events by MedDRA 
System Organ Class and Preferred Term - by 
Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
 
3.2.7.2 
Summary of Any Grade 3 or Higher INCAGN01876 
Treatment-Related Adverse Events by MedDRA 
System Organ Class and Preferred Term - by 
Treatment Group and Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.2.7.3 
Summary of Any Grade 3 or Higher Nivolumab 
Treatment-Related Adverse Events by MedDRA 
System Organ Class and Preferred Term - by 
Treatment Group and Dose 
Phase 1 FAS 
Nivolumab 
Population 
X 
 
3.2.7.4 
Summary of Any Grade 3 or Higher Nivolumab 
Treatment-Related Adverse Events by MedDRA 
System Organ Class and Preferred Term - by 
Treatment Group and Tumor Type 
Phase 2 FAS 
Nivolumab 
Population 
X 
 
3.2.7.5 
Summary of Any Grade 3 or Higher Ipilimumab 
Treatment-Related Adverse Events by MedDRA 
System Organ Class and Preferred Term - by 
Treatment Group and Dose 
Phase 1 FAS 
Ipilimumab 
Population 
X 
 
3.2.7.6 
Summary of Any Grade 3 or Higher Ipilimumab 
Treatment-Related Adverse Events by MedDRA 
System Organ Class and Preferred Term - by 
Treatment Group and Tumor Type 
Phase 2 FAS 
Ipilimumab 
Population 
X 
 
3.2.8.1 
Summary of Any INCAGN01876 Treatment-Related 
Adverse Events With a Fatal Outcome by MedDRA 
System Organ Class and Preferred Term - by 
Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
 
3.2.8.2 
Summary of Any INCAGN01876 Treatment-Related 
Adverse Events With a Fatal Outcome by MedDRA 
System Organ Class and Preferred Term - by 
Treatment Group and Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.2.8.3 
Summary of Any Nivolumab Treatment-Related 
Adverse Events With a Fatal Outcome by MedDRA 
System Organ Class and Preferred Term - by 
Treatment Group and Dose 
Phase 1 FAS 
Nivolumab 
Population 
X 
 
3.2.8.4 
Summary of Any Nivolumab Treatment-Related 
Adverse Events With a Fatal Outcome by MedDRA 
System Organ Class and Preferred Term - by 
Treatment Group and Tumor Type 
Phase 2 FAS 
Nivolumab 
Population 
X 
 


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Table No. 
Title 
Population 
Standard 
In-Text 
3.2.8.5 
Summary of Any Ipilimumab Treatment-Related 
Adverse Events With a Fatal Outcome by MedDRA 
System Organ Class and Preferred Term - by 
Treatment Group and Dose 
Phase 1 FAS 
Ipilimumab 
Population 
X 
 
3.2.8.6 
Summary of Any Ipilimumab Treatment-Related 
Adverse Events With a Fatal Outcome by MedDRA 
System Organ Class and Preferred Term - by 
Treatment Group and Tumor Type 
Phase 2 FAS 
Ipilimumab 
Population 
X 
 
3.2.9.1 
Summary of Serious Treatment-Emergent Adverse 
Events by MedDRA System Organ Class and Preferred 
Term - by Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
 
3.2.9.2 
Summary of Serious Treatment-Emergent Adverse 
Events by MedDRA System Organ Class and Preferred 
Term - by Treatment Group and Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.2.10.1 
Summary of Serious Treatment-Emergent Adverse 
Events by MedDRA Preferred Term in Decreasing 
Order of Frequency - by Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
X 
3.2.10.2 
Summary of Serious Treatment-Emergent Adverse 
Events by MedDRA Preferred Term in Decreasing 
Order of Frequency - by Treatment Group and Tumor 
Type 
Phase 2 FAS 
Population 
X 
X 
3.2.11.1 
Summary of INCAGN01876 Treatment-Related 
Serious Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term - by 
Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
 
3.2.11.2 
Summary of INCAGN01876 Treatment-Related 
Serious Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term - by 
Treatment Group and Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.2.11.3 
Summary of Nivolumab Treatment-Related Serious 
Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term - by 
Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
 
3.2.11.4 
Summary of Nivolumab Treatment-Related Serious 
Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term - by 
Treatment Group and Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.2.11.5 
Summary of Ipilimumab Treatment-Related Serious 
Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term - by 
Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
 
3.2.11.6 
Summary of Ipilimumab Treatment-Related Serious 
Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term - by 
Treatment Group and Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.2.12.1 
Summary of Non-Serious Treatment-Emergent 
Adverse Events by MedDRA System Organ Class and 
Preferred Term - by Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
 
3.2.12.2 
Summary of Non-Serious Treatment-Emergent 
Adverse Events by MedDRA System Organ Class and 
Preferred Term - by Treatment Group and Tumor Type 
Phase 2 FAS 
Population 
X 
 


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Table No. 
Title 
Population 
Standard 
In-Text 
3.2.13.1 
Summary of Treatment-Emergent Adverse Events 
Leading to INCAGN01876 Dose Reduction by 
MedDRA System Organ Class and Preferred Term - by 
Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
 
3.2.13.2 
Summary of Treatment-Emergent Adverse Events 
Leading to INCAGN01876 Dose Reduction by 
MedDRA System Organ Class and Preferred Term - by 
Treatment Group and Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.2.14.1 
Summary of Treatment-Emergent Adverse Events 
Leading to Any Dose Interruption by MedDRA System 
Organ Class and Preferred Term - by Treatment Group 
and Dose 
Phase 1 FAS 
Population 
X 
 
3.2.14.2 
Summary of Treatment-Emergent Adverse Events 
Leading to Any Dose Interruption by MedDRA System 
Organ Class and Preferred Term - by Treatment Group 
and Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.2.15.1 
Summary of Treatment-Emergent Adverse Events 
Leading to Discontinuation of INCAGN01876 by 
MedDRA System Organ Class and Preferred Term - by 
Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
 
3.2.15.2 
Summary of Treatment-Emergent Adverse Events 
Leading to Discontinuation of INCAGN01876 by 
MedDRA System Organ Class and Preferred Term - by 
Treatment Group and Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.2.16.1 
Summary of Treatment-Emergent Immune-Related 
Adverse Events (Investigator Identified) by MedDRA 
System Organ Class and Preferred Term - by 
Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
 
3.2.16.2 
Summary of Treatment-Emergent Immune-Related 
Adverse Events (Investigator Identified) by MedDRA 
System Organ Class and Preferred Term - by 
Treatment Group and Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.2.17.1 
Summary of Treatment-Emergent Immune-Related 
Adverse Events (Sponsor Identified) by MedDRA 
System Organ Class and Preferred Term - by 
Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
 
3.2.17.2 
Summary of Treatment-Emergent Immune-Related 
Adverse Events (Sponsor Identified) by MedDRA 
System Organ Class and Preferred Term - by 
Treatment Group and Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.2.18.1 
Summary of Treatment-Emergent Immune-Related 
Adverse Events (Investigator Identified) by MedDRA 
System Organ Class, Preferred Term, and Maximum 
Severity - by Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
 
3.2.18.2 
Summary of Treatment-Emergent Immune-Related 
Adverse Events (Investigator Identified) by MedDRA 
System Organ Class, Preferred Term, and Maximum 
Severity - by Treatment Group and Tumor Type 
Phase 2 FAS 
Population 
X 
 


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Table No. 
Title 
Population 
Standard 
In-Text 
3.2.19.1 
Summary of Grade 3 or Higher Treatment-Emergent 
Immune-Related Adverse Events (Investigator 
Identified) by MedDRA System Organ Class and 
Preferred Term - by Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
X 
3.2.19.2 
Summary of Grade 3 or Higher Treatment-Emergent 
Immune-Related Adverse Events (Investigator 
Identified) by MedDRA System Organ Class and 
Preferred Term - by Treatment Group and Tumor Type 
Phase 2 FAS 
Population 
X 
X 
3.2.20 
Life Table Estimate of Time to First Grade 3 or Higher 
Treatment-Emergent Adverse Event - by Treatment 
Group and Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.2.21.1 
Summary of Adverse Events With a Fatal Outcome by 
System Organ Class and Preferred Term - by 
Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
 
3.2.21.2 
Summary of Adverse Events With a Fatal Outcome by 
System Organ Class and Preferred Term - by 
Treatment Group and Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.2.22.1 
Summary of Infusion Reactions - by Treatment Group 
and Dose 
Phase 1 FAS 
Population 
 
 
3.2.22.2 
Summary of Infusion Reactions - by Treatment Group 
and Tumor Type 
Phase 2 FAS 
Population 
 
 
3.3 Laboratory 
3.3.1 
Summary of Laboratory Values - Hematology 
Phase 2 FAS 
Population 
X 
 
3.3.2.1 
Summary of Treatment Emergent Worsening 
Hematology Laboratory Values in CTC Grade - To the 
Worst Abnormal Value  
Phase 1 FAS 
Population 
X 
 
3.3.2.2 
Summary of Treatment Emergent Worsening 
Hematology Laboratory Values in CTC Grade - To the 
Worst Abnormal Value 
Phase 2 FAS 
Population 
X 
 
3.3.3 
Summary of Laboratory Values - Chemistry 
Phase 2 FAS 
Population 
X 
 
3.3.4.1 
Summary of Treatment Emergent Worsening 
Chemistry Laboratory Values in CTC Grade - To the 
Worst Abnormal Value 
Phase 1 FAS 
Population 
X 
 
3.3.4.2 
Summary of Treatment Emergent Worsening 
Chemistry Laboratory Values in CTC Grade - To the 
Worst Abnormal Value 
Phase 2 FAS 
Population 
X 
 
3.4 Vital Signs 
3.4.1.1 
Summary of Systolic Blood Pressure (mmHg) 
Phase 1 FAS 
Population 
X 
 
3.4.1.2 
Summary of Systolic Blood Pressure (mmHg) - by 
Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.4.2.1 
Summary of Diastolic Blood Pressure (mmHg) 
Phase 1 FAS 
Population 
X 
 
3.4.2.2 
Summary of Diastolic Blood Pressure (mmHg) - by 
Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.4.3.1 
Summary of Pulse (bpm) 
Phase 1 FAS 
Population 
X 
 


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Table No. 
Title 
Population 
Standard 
In-Text 
3.4.3.2 
Summary of Pulse (bpm) - by Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.4.4.1 
Summary of Respiration Rate (bpm) 
Phase 1 FAS 
Population 
X 
 
3.4.4.2 
Summary of Respiration Rate (bpm) - by Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.4.5.1 
Summary of Body Temperature (°C) 
Phase 1 FAS 
Population 
X 
 
3.4.5.2 
Summary of Body Temperature (°C) - by Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.4.6.1 
Summary of Weight (kg) 
Phase 1 FAS 
Population 
X 
 
3.4.6.2 
Summary of Weight (kg) - by Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.5 ECG 
3.5.1.1 
Summary of PR Interval (msec) From Local Lab 
12-Lead ECG 
Phase 1 FAS 
Population 
X 
 
3.5.1.2 
Summary of PR Interval (msec) From Local Lab 
12-Lead ECG - by Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.5.2.1 
Summary of RR Interval (msec) From Local Lab 
12-Lead ECG 
Phase 1 FAS 
Population 
X 
 
3.5.2.2 
Summary of RR Interval (msec) From Local Lab 
12-Lead ECG - by Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.5.3.1 
Summary of QT Interval (msec) From Local l Lab 
12-Lead ECG 
Phase 1 FAS 
Population 
X 
 
3.5.3.2 
Summary of QT Interval (msec) From Local Lab 
12-Lead ECG - by Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.5.4.1 
Summary of QRS Interval (msec) From Local Lab 
12-Lead ECG 
Phase 1 FAS 
Population 
X 
 
3.5.4.2 
Summary of QRS Interval (msec) From Local Lab 
12-Lead ECG - by Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.5.5.1 
Summary of QTcB Interval (msec) From Local Lab 
12-Lead ECG 
Phase 1 FAS 
Population 
X 
 
3.5.5.2 
Summary of QTcB Interval (msec) From Local Lab 
12-Lead ECG - by Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.5.6.1 
Summary of QTcF Interval (msec) From Local Lab 
12-Lead ECG 
Phase 1 FAS 
Population 
X 
 
3.5.6.2 
Summary of QTcF Interval (msec) From Local Lab 
12-Lead ECG- by Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.5.7.1 
Summary of JTc Interval (msec) From Local Lab 
12-Lead ECG 
Phase 1 FAS 
Population 
 
 
3.5.7.2 
Summary of JTc Interval (msec) From Local Lab 
12-Lead ECG- by Tumor Type 
Phase 2 FAS 
Population 
X 
 
3.5.8.1 
Summary of Heart Rate (beats/min) From Local Lab 
12-Lead ECG 
Phase 1 FAS 
Population 
X 
 
3.5.8.2 
Summary of Heart Rate (beats/min) From Local Lab 
12-Lead ECG - by Tumor Type 
Phase 2 FAS 
Population 
X 
 


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Table No. 
Title 
Population 
Standard 
In-Text 
3.5.9.1 
Summary of Alert Values of PR, QRS, QT, RR, and 
QTcF Interval Values From Local Lab 12-Lead ECG 
by Visit - by Treatment Group and Dose 
Phase 1 FAS 
Population 
X 
X 
3.5.9.2 
Summary of Alert Values of PR, QRS, QT, RR, and 
QTcF Interval Values From Local Lab 12-Lead ECG 
by Visit - by Treatment Group and Tumor Type 
Phase 2 FAS 
Population 
X 
X 
Figures 
Figure No. 
Title 
Population 
4.1 Efficacy 
4.1.1 
Kaplan-Meier Estimates of Progression-Free Survival 
Phase 2 FAS Population 
4.1.2 
Kaplan-Meier Estimates of Overall Survival 
Phase 2 FAS Population 
4.1.3.1 
Swim Plot of Duration of Response - by Treatment Group 
Phase 1 FAS Population 
4.1.3.2 
Swim Plot of Duration of Response - by Treatment Group and Tumor 
Type 
Phase 2 FAS Population 
4.1.4.1 
Waterfall Plot of Percentage Change From Baseline in Sum of Target 
Lesions - by Treatment Group and Dose 
Phase 1 FAS Population 
4.1.4.2 
Waterfall Plot of Percentage Change From Baseline in Sum of Target 
Lesions - by Treatment Group and Tumor Type 
Phase 2 FAS Population 
4.1.5.1 
Spider Plot of Percentage Change From Baseline in Sum of Target 
Lesions - by Treatment Group  
Phase 1 FAS Population 
4.1.5.2 
Spider Plot of Percentage Change From Baseline in Sum of Target 
Lesions - by Treatment Group and Tumor Type 
Phase 2 FAS Population 
4.90 Safety Data 
4.90.1.1 
Bar Chart for Incidence of Treatment Emergent Adverse Events of Special 
Interest - by Treatment Group and Dose 
Phase 1 FAS Population 
4.90.1.2 
Bar Chart for Incidence of Treatment Emergent Adverse Events of Special 
Interest - by Treatment Group and Tumor Type 
Phase 2 FAS Populaion 
40.90.2.1 
Line Graph of Selected Laboratory Values by Study Visit 
Phase 1 FAS Population 
40.90.2.2 
Line Graph of Selected Laboratory Values by Study Visit 
Phase 2 FAS Population 
40.90.3.1 
Box-and-Whisker Plot of Selected Laboratory Values by Study Visit 
Phase 1 FAS Population 
40.90.3.1 
Box-and-Whisker Plot of Selected Laboratory Values by Study Visit 
Phase 2 FAS Population 
Listings 
Listing No. 
Title 
2.1 Discontinued Subjects (Subject Disposition) 
2.1.1 
Subject Enrollment and Disposition Status 
2.1.2 
Subject Inclusion and Exclusion Criteria Violations 
2.2 Protocol Deviation 
2.2.1 
Protocol Deviations and Violations 
2.3 Data Excluded From
Efficacy, and/or Safety Analyses 
2.3.1 
Analysis Population 
2.4 Demography and Baseline (Including Prior and Concomitant Medications) 
2.4.1 
Demographic  
2.4.2.1 
Baseline Disease Characteristics for Phase 1 Solid Tumor Types 
2.4.2.2 
Baseline Disease Characteristics for Phase 2 – by Tumor Type 


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Listing No. 
Title 
2.4.3 
Disease History 
2.4.4 
Prior Radiation Treatment 
2.4.5 
Prior Systemic Therapy 
2.4.6 
Prior Surgery or Surgical Procedure 
2.4.7 
Medical History 
2.4.8 
Prior and Concomitant Medication 
2.5 Efficacy 
 
2.5.1.1 
Best Overall Response With Confirmed CRs and PRs Under RECIST v1.1 
2.5.1.2 
Best Overall Response With Unconfirmed CRs and PRs Under RECIST v1.1 
2.5.2.1 
Best Overall Response With Confirmed CRs and PRs Under mRECIST v1.1 
2.5.2.2 
Best Overall Response With Unconfirmed CRs and PRs Under mRECIST v1.1 
2.5.3 
Overall Response Assessment 
2.5.4 
Response Assessment: Target Lesions 
2.5.5 
Response Assessment: Non-Target Lesions 
2.5.6 
Response Assessment: New Lesions 
2.5.7 
ECOG status 
 
  
2.6 Adverse Events (and Exposure) 
2.6.1.1 
Study Drug Administration for INCAGN01876  
2.6.1.2 
Study Treatment Administration for Nivolumab 
2.6.1.3 
Study Treatment Administration for Ipilimumab 
2.6.2 
Adverse Events 
2.6.3 
Dose-Limiting Toxicities 
2.6.4 
Serious Adverse Events 
2.6.6 
Fatal Adverse Events 
2.6.8 
Adverse Events Leading to Discontinuation of INCAGN01876 
2.6.9 
Investigator-Identified Immune-Related Adverse Events 
2.6.10 
Sponsor-Identified Immune-Related Adverse Events 
2.6.11 
Infusion Reactions  
2.7 Laboratory Data 
2.7.1 
Clinical Laboratory Values - Hematology 
2.7.2 
Clinical Laboratory Values - Chemistry 
2.7.3 
Abnormal Clinical Laboratory Values 
 
 
2.8 Vital Signs 
2.8.1 
Vital Signs 
2.8.2 
Abnormal Vital Sign Values 
2.8.3 
Alert Vital Sign Values 
2.9 ECG 
2.9.1 
12-Lead Local ECG Values 
2.9.2 
Abnormal 12-Lead Local ECG Values 
2.9.3 
Alert 12-Lead Local ECG Values 
2.10 Physical Examination 
2.10.1 
Body Weight 


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APPENDIX B. TECHNICAL REPORT FOR INTEGRATED BAYESIAN 
FUTILITY ANALYSIS  
Introduction 
In this document, we present a strategy for pooling information across the tumor types and 
sequencing strategies defined in Section 3.  The strategy is based on Simon et al (2016).  The 
Bayesian pooling strategy will be used to carry out interim futility analyses and end-of-study 
efficacy analyses for each cohort.  We begin with an introduction to the overall study design, and 
then we present simulation results and operating characteristics that illustrate the application of 
the Simon et al (2016) method in Part 2 of this study. 
Phase 2 of the study will evaluate the efficacy of the recommended dose of INCAGN01876 as 
part of a doublet combination with the approved immunotherapy nivolumab and as part of a 
triplet combination with the approved immunotherapies nivolumab and ipilimumab.  Subjects 
with endometrial, gastric, and SCCHN tumors will be evaluated in each of the doublet and triplet 
combinations.  In addition, each of the doublet and triplet combinations will be tested using 
3 dose-sequencing strategies:  concurrent dosing of INCAGN01876 and immunotherapy, 
INCAGN01876 run-in Q2W for 2 doses followed by immunotherapy, and INCAGN01876 
run-in Q2W for 2 doses followed by concurrent dosing of INCAGN01876 and immunotherapy. 
In total, the study design for Phase 2 will test 18 unique tumor type (within doublet or triplet) 
and sequencing strategy cohorts.  Each of the 18 cohorts will be evaluated by Simon 2-Stage 
design (Simon 1989).  All sequencing strategies for a particular tumor type and doublet or triplet 
combination will use the same Simon 2-Stage design. 
Table 12 shows the dose sequencing strategy and tumor type–specific strategy for each of the 
18 cohorts used for pooling in the integrated Bayesian analysis.  It is believed that activity or the 
lack of activity within any of the tumor types in a particular sequencing strategy will provide 
information about the activity in other tumor types in that sequencing strategy.  It is also believed 
that activity or the lack of activity in 1 of the sequences tested on a specific tumor type will 
provide information about the activity in the other sequences tested on the same tumor type. 
For the analysis within sequencing strategies, there will be 6 strata within each sequencing 
strategy.  For the analysis within tumor types, there will be 3 strata within each tumor type. 
Parameters to be specified a priori include λ, the probability of homogeneity, which controls the 
amount of borrowing; γ, the probability of activity in any stratum; and a vector of probabilities 
of length k equal to the number of strata, specifying individual probabilities of success in each 
stratum when the strata are not homogeneous, Pr [p = q].  Here, the p vector represents the 
probability of activity in each stratum, and q is the outcome vector for p, each entry of q is p1 or 
p0, corresponding to the probabilities of activity or inactivity, respectively, in the individual 
strata.  This leads to 2k possibilities for the Pr [p = q] vector.  The individual p1 vectors are the 
target response rates from the Simon 2-Stage design for the given tumor types, and the individual 
p0 vectors are the unacceptable response rates from the same Simon 2-Stage designs.  To clarify, 
the Pr [p = q] vector is used in the calculation of the likelihood, but not in the calculation of the 
prior PoS. 


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To calculate prior PoS in any given cohort, we first determine all 2k permutations of successes 
and failures among the k cohorts and store these permutations in a matrix, m.  Below is an 
example of the 8 × 3 m matrix for 3 strata.  The rows of the m matrix represent the 
permutations, the columns represent the cohorts, and each entry in a row of 1 or 0 represents 
success or failure, respectively, for that cohort in the corresponding permutation. 
m =
⎣
⎢
⎢
⎢
⎢
⎢
⎡0
0
0
1
0
0
0
1
0
1
0
1
1
1
0
0
1
1
0
0
1
1
1
1⎦
⎥
⎥
⎥
⎥
⎥
⎤
 
For rows 2 through 2k-1 of the permutation matrix, where i represents the ith row and j 
represents the jth column, the prior PoS is defined as follows: 
PoS = (1 −λ) × γ∑
mij
2k
i=1
(1 −γ)∑
1−mij
2k
i=1
, 
where 1 −λ is the probability that the cohorts are independent; γ is the probability of activity; 
∑
mij
2k
i=1
 is the sum of the number of active cohorts under all permutations; 1 −γ is the 
probability of inactivity; and ∑
1 −mij
2k
i=1
 is the sum of the number of inactive cohorts under all 
permutations. 
For row 1, which represents the case in which all cohorts are inactive, we add in the probability 
that the cohorts are correlated times the probability of inactivity: 
PoS = (1 −λ) × γ∑
mij
2k
i=1
(1 −γ)∑
1−mij
2k
i=1
+ λ(1 −γ). 
For row 2k, which represents the case in which all cohorts are active, we add in the probability 
that the cohorts are correlated times the probability of activity: 
PoS = (1 −λ) × γ∑
mij
2k
i=1
(1 −γ)∑
1−mij
2k
i=1
+  λγ. 
Posterior PoS calculations based on sharing within the tumor types and within the sequencing 
strategies will be updated each time a subject with the tumor type of interest enrolls in the study 
using data already collected from subjects already on the study. 


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The posterior probabilities depend on the number of responses and sample sizes in each of the 
strata at the time, denoted by the vectors r and n respectively.  The posterior PoS in tumor type i 
and sequence strategy j is proportional to the prior probability times the likelihood of the 
response data observed up to that point if the response numbers are given by the r vector, if the 
sample sizes are given by the n vector, and if qij is p1 times the same likelihood of the response 
data observed up to that point qij is p0: 
𝑃𝑃𝑃= Pr(𝒑= 𝒒|𝜆, 𝛾, 𝒓, 𝒏)
= ቆ(1 −𝜆) × 𝛾∑
𝑚𝑖𝑖
2𝑘
𝑖=1
(1 −𝛾)∑
1−𝑚𝑖𝑖
2𝑘
𝑖=1
ቇ
× ෑෑ
𝑞𝑖𝑖
𝑟𝑖𝑖൫1 −𝑞𝑖𝑖൯
𝑛𝑖𝑖−𝑟𝑖𝑖
𝑗,𝑞𝑖𝑖=𝑝1
× ෑෑ
𝑞𝑖𝑖
𝑟𝑖𝑖൫1 −𝑞𝑖𝑖൯
𝑛𝑖𝑖−𝑟𝑖𝑖
𝑗,𝑞𝑖𝑖=𝑝0
𝑖
𝑖
 
As an example of the PoS calculation, we look at a simplified example with 3 strata in Table B1.  
Suppose that we observe the following results for the evaluable subjects in a study with 
3 separate Simon 2-Stage designs with target rates of 0.25 and unacceptable rates of 0.05.  The 
optimal Simon 2-Stage design with these criteria has an interim sample size of 19, total sample 
size of 55, r = 3, r = 12.  The PoS calculation for each controls the degree of sharing of data 
between the strata and γ as the prior probability of activity for a given cohort.  Note that the 
parameter λ has a direct relationship with the calculated PoS value across the 3 stratum. 
Table B1: 
Example PoS Calculations for 3 Stratum 
Stratum 
1 
2 
3 
Responders/evaluable subjects 
6/20 
3/10 
1/5 
PoS based on λ = 0.5 and  γ = 0.33 
0.99 
0.98 
0.90 
PoS based on λ = 0.05 and  γ = 0.33 
0.99 
0.93 
0.18 
For the purposes of this analysis, we will specify a single value for λ and γ, so that the rate of 
sharing within sequences and tumor types will be equal, and the prior PoS assumed within strata 
in the pooling strategies will be equal.  The PoS in tumor type (tumor type i and sequencing 
strategy j) will be denoted by PoS1ij, and the PoS within sequencing strategy (tumor type i and 
sequencing strategy j) will be denoted by PoS2ij. 
Based on the results of the 2 calculated posterior PoS values, a tumor-sequence pair (i,j) will be 
considered open for randomization if either PoS1ij  or PoS2ij  is greater than 20%.  Otherwise, 
the tumor-sequence pair will be suspended with the possibility of being re-opened after more 
data have accrued and subsequent posterior PoS values are greater than 20% for the 
tumor-sequence pair. 
At the end of the study, overall PoS tests will be performed using both PoS1ij and PoS2ij.  A 
tumor-sequence strategy will be considered successful at the end of the study if either PoS1ij or 
PoS2ij > 80%. 


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Each time a subject with the tumor type of interest is enrolled, 2 PoS calculations will be 
performed using the evaluable subjects:  the PoS in tumor type (tumor type i and sequencing 
strategy j), PoS1ij, and PoS within sequencing strategy (tumor type i and sequencing strategy j), 
PoS2ij. 
Simulations and Operating Characteristics 
Computer simulations were conducted in R to compare the operating characteristics of the 
Bayesian basket trial design with the operating characteristics of 18 separate Simon 2-Stage 
designs.  We investigated 6 scenarios that would represent different configurations of null and 
alternative hypotheses (corresponding to inactivity of drug and activity of drug) within the 
sequencing strategies and tumor types.  For the global null hypothesis of no activity in any 
cohort (Scenario 1), 2500 replications were performed.  All other scenario results were simulated 
using 1000 replications. 
In the computer simulations, we assumed the prior probability of correlation between cohorts 
within tumor types and sequencing strategies to be λ = 0.4 and prior probability of activity to be 
γ = 0.4. 
The Simon 2-Stage designs used in the simulations are given in Table 2.  The 𝑝1 and 𝑝0 values 
are assumed not to change with sequencing strategy.  For example, for each of the 3 sequencing 
strategies tested on the SCCHN doublet, 𝑝1 = 0.35 and 𝑝0 = 0.15.  The total sample sizes if 
each cohort reached full enrollment are given by the n column in Table 2. 
Within the simulations, a tumor-sequence pair (i, j) was stopped if neither 𝑃𝑃𝑃1𝑖𝑖 nor 𝑃𝑃𝑃2𝑖𝑖 
was ≥ 20% at any point.  In addition, the first stage rule for the Simon 2-stage design was also 
applied where enrollment was halted unless more than r1 of the first n1 subjects responded to 
treatment within a tumor-sequence pair. The method rejected the null hypothesis of no activity in 
a cohort at the end of the study if either 𝑃𝑃𝑃1𝑖𝑖 or 𝑃𝑃𝑃2𝑖𝑖 > 80%. 
For purposes of the simulation, tumor responses were programmed to occur 16 weeks after start 
of treatment.  A 7-month period was assumed between the opening of the doublet and triplet 
tumor type cohorts.  During the first 7 months, subjects were equally distributed among 
endometrial, gastric, and SCCHN tumor types and subjects of each tumor type were randomly 
assigned to the 3 sequence strategies.  After the first 7 months, the triplet tumor type cohorts 
opened, subjects were still equally distributed among endometrial, gastric, and SCCHN tumor 
types and were sequentially assigned to the doublet and triplet sequencing strategy–specific 
treatment groups that were available after the interim futility and Simon 2-Stage futility rules 
were applied.  Enrollment in each tumor type was assumed to occur over a 33-month period with 
subjects equally distributed between the 3 tumor types over that period and rates of enrollment 
increasing over the length of enrollment.  Enrollment was generated by an exponential(0.7) 
curve.  Projected maximum enrollment by quarter is defined in Table B2. 


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CONFIDENTIAL 
Table B2: 
Simulated Enrollment by Quarter-Year From Trial Start 
Quarter # 
1 
2 
3 
4 
5 
6 
Enrollment 
28 
76 
136 
207 
284 
369 
Quarter # 
7 
8 
9 
10 
11 
 
Enrollment 
460 
557 
658 
766 
873 
 
The operating characteristics obtained from the simulations are given in Table B3.  Compared 
against 18 separate Simon 2-Stage designs, the Bayesian basket trial offers a significant 
reduction in sample size and close to 10% Type I error control.  The individual Simon 2-Stage 
designs are considered to be independent trials and would offer no attempt to control Type I 
error.  The Bayesian basket trial also offers high power (in most cases more than 97%) to reject 
the null hypotheses of no activity in the cohorts when activity is present.  In Scenario 6, when 
only 1 of the 18 cohorts has activity, the Bayesian basket trial still has 63.7% power to reject the 
null hypothesis for that cohort. 


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INCAGN 1876-201 Statistical Analysis Plan 
05 DEC 2017 
CONFIDENTIAL 
Table B3: 
Operating Characteristics Based on Simulation Results 
Scenario 
Expected 
Sample 
Size 
Probability 
of a Single 
False 
Positive 
Result 
Expected 
Number of 
False 
Positive 
Results 
Power to 
Reject 
≥ 1 True 
Alternative 
Hypothesis 
Expected 
Number of 
True 
Rejections 
Number of 
True 
Alternative 
Hypotheses 
Expected 
Sample 
Size for 
Simon 
2-Stage 
Design 
Expected 
Number of 
Correct 
Rejections 
for Simon 
2-Stage 
Design 
Expected 
Number of  
False 
Rejections 
for Simon 
2-Stage 
Design 
Global null hypothesis 
355.2 
0.0876 
0.104 
– 
– 
0 
457.2 
– 
0.9 
Global alternative 
hypothesis 
807.0 
– 
– 
> 0.999 
16.3 
18 
807.7 
15.3 
– 
Alternative hypotheses in 
Tumor Type 1, null for 
Tumor Types 2 and 3 
534.8 
0.135 
0.153 
> 0.999 
5.0 
6 
574.7 
5.1 
0.6 
Alternative hypothesis in 
Sequence 1, null for 
Sequences 2 and 3 
527.9 
0.150 
0.162 
> 0.999 
5.4 
6 
574.0 
5.1 
0.6 
Alternative hypothesis in 
Tumor Type 1 in triplet, 
all others null 
444.5 
0.127 
0.139 
0.978 
2.5 
3 
515.7 
2.55 
0.75 
Alternative hypothesis in 
Tumor Type 1 in triplet 
Sequence 1, all others null 
387.7 
0.123 
0.136 
0.637 
0.6 
1 
476.7 
0.85 
0.85