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Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Ipilimumab

Glucocorticoids

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

Participants received INCAGN01876 3.0 mg/kg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Participants received INCAGN01876 5.0 mg/kg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Participants received INCAGN01876 10.0 mg/kg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

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.

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.

Participants received INCAGN01876 1.0 mg/kg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV every 6 weeks (Q6W).

Participants received INCAGN01876 3.0 mg/kg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV Q6W.

Participants received INCAGN01876 5.0 mg/kg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV Q6W.

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.

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.

Participants with gastric cancer (GC) received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

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.

Participants with cervical cancer (CC) received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Participants with PD-1/PD-L1 relapsed melanoma received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

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.

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 ().

INCAGN01876

Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Ipilimumab will be administered IV at the protocol-defined dose according to assigned treatment group.

John E. Janik, MD

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.

Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of INCAGN01876 Combined With Immune Therapies in Advanced or Metastatic Malignancies

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

An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study medication.

ORR was defined as the percentage of participants with a best overall response of confirmed complete response (CR) or partial response (PR), determined by investigator assessment of radiographic disease assessments per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.

ORR was defined as the percentage of participants with a best overall response of unconfirmed CR or PR, determined by investigator assessment of radiographic disease assessments per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.

ORR was defined as the percentage of participants with a best overall response of unconfirmed CR or PR, determined by investigator assessment of radiographic disease assessments per mRECIST v1.1. The response of target lesions was evaluated from the percentage change in the sum of the diameters of the viable portions (portions enhanced during the arterial phase). CR: Disappearance of any intratumoral arterial enhancement during in target lesions, disappearance of all non-target lesions, and no appearance of any new lesions. PR: ≥30% of the sum of the diameters of viable portions (enhancement on arterial phase) of target lesions taking as reference the Baseline sum, no new lesions, and no progression of non-target lesions.

ORR was defined as the percentage of participants with a best overall response of confirmed CR or PR, determined by investigator assessment of radiographic disease assessments per mRECIST v1.1. The response of target lesions was evaluated from the percentage change in the sum of the diameters of the viable portions (portions enhanced during the arterial phase). CR: Disappearance of any intratumoral arterial enhancement during in target lesions, disappearance of all non-target lesions, and no appearance of any new lesions. PR: ≥30% of the sum of the diameters of viable portions (enhancement on arterial phase) of target lesions taking as reference the Baseline sum, no new lesions, and no progression of non-target lesions.

DOR was defined as the time from the first overall response contributing to an unconfirmed objective response (CR or PR) to the earlier of the participant's death from any cause or the first assessment of PD, determined by investigator assessment of radiographic disease assessment per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion.

DOR was defined as the time from the first overall response contributing to a confirmed objective response (CR or PR) to the earlier of the participant's death from any cause or the first assessment of PD, determined by investigator assessment of radiographic disease assessment per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion.

DOR was defined as the time from the first unconfirmed overall response contributing to an unconfirmed objective response (CR or PR) to the earlier of the participant's death from any cause or the first confirmed assessment of PD, determined by investigator assessment of radiographic disease assessment per mRECIST v1.1. The response of target lesions was evaluated from the percentage change in the sum of the diameters of the viable portions (portions enhanced during the arterial phase). CR: Disappearance of any intratumoral arterial enhancement during in target lesions, disappearance of all non-target lesions, and no appearance of any new lesions. PR: ≥30% of the sum of the diameters of viable portions (enhancement on arterial phase) of target lesions taking as reference the Baseline sum, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion.

DOR was defined as the time from the first overall response contributing to a confirmed objective response (CR or PR) to the earlier of the participant's death from any cause or the first assessment of PD, determined by investigator assessment of radiographic disease assessment per mRECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion.

DCR was defined as the percentage of participants with a best overall response of unconfirmed CR, unconfirmed PR, or stable disease (SD; ≥49 days), determined by investigator assessment of radiographic disease assessments per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD.

DCR was defined as the percentage of participants with a best overall response of confirmed CR, confirmed PR, or SD (≥49 days), determined by investigator assessment of radiographic disease assessments per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD.

DCR was defined as the percentage of participants with a best overall response of confirmed CR, confirmed PR, or SD (≥49 days), determined by investigator assessment of radiographic disease assessments per mRECIST v1.1. The response of target lesions was evaluated from the percentage change in the sum of the diameters of the viable portions (portions enhanced during the arterial phase). CR: Disappearance of any intratumoral arterial enhancement during in target lesions, disappearance of all non-target lesions, and no appearance of any new lesions. PR: ≥30% of the sum of the diameters of viable portions (enhancement on arterial phase) of target lesions taking as reference the Baseline sum, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD.

Duration of disease control (CR, PR, and SD \[≥49 days\]) was measured from the start of treatment until PD or death from any cause, if occurring sooner than progression, determined by investigator assessment of radiographic disease per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD.

Duration of disease control (CR, PR, and SD \[≥49 days\]) was measured from the start of treatment until PD or death from any cause, if occurring sooner than progression, determined by investigator assessment of radiographic disease per RECIST v1.1. The response of target lesions was evaluated from the percentage change in the sum of the diameters of the viable portions (portions enhanced during the arterial phase). CR: Disappearance of any intratumoral arterial enhancement during in target lesions, disappearance of all non-target lesions, and no appearance of any new lesions. PR: ≥30% of the sum of the diameters of viable portions (enhancement on arterial phase) of target lesions taking as reference the Baseline sum, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD.

Duration of disease control (CR, PR, and SD \[≥49 days\]) was measured from the start of treatment until PD or death from any cause, if occurring sooner than progression, determined by investigator assessment of radiographic disease per RECIST v1.1. The response of target lesions was evaluated from the percentage change in the sum of the diameters of the viable portions (portions enhanced during the arterial phase). CR: Disappearance of any intratumoral arterial enhancement during in target lesions, disappearance of all non-target lesions, and no appearance of any new lesions. PR: ≥30% of the sum of the diameters of viable portions (enhancement on arterial phase) of target lesions taking as reference the Baseline sum, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD. \[

According to RECIST 1.1, PFS was defined as the length of time between the Baseline visit (Day 1) and the earlier of death or the first assessment of PD, as determined by investigator assessment of objective radiographic disease assessments.

According to mRECIST 1.1, PFS was defined as the length of time between the Baseline visit (Day 1) and the earlier of the participant's death or the first confirmed assessment of PD, as determined by investigator assessment of objective radiographic disease assessments. The response of target lesions was evaluated from the percentage change in the sum of the diameters of the viable portions (portions enhanced during the arterial phase).

Overall survival was defined as the interval between the Baseline visit (Day 1) and the date of death due to any cause.

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study medication.

Incyte Biosciences International Sàrl

Treatment-emergent adverse events (TEAEs), defined as adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study medication, were monitored for at least 60 days after the last dose of study treatment or until the start of new anticancer therapy, whichever occurred first (up to 27.4 months). All-Cause Mortality was monitored for the duration of the study (up to 44.7 months).

Phase 1 Group A: INCAGN01876 1.0 mg/kg Q2W + Nivolumab 240 mg Q2W

Phase 1 Group A: INCAGN01876 3.0 mg/kg Q2W + Nivolumab 240 mg Q2W

Phase 1 Group A: INCAGN01876 5.0 mg/kg Q2W + Nivolumab 240 mg Q2W

Phase 1 Group A: INCAGN01876 10.0 mg/kg Q2W + Nivolumab 240 mg Q2W

Participants received INCAGN01876 1.0 mg/kg administered IV Q2W for a total of 2 doses as run-in, followed by nivolumab 240 mg administered IV Q2W starting at Cycle 3.

Phase 1 Group B: INCAGN01876 1.0 mg/kg Q2W, Then Nivolumab 240 mg Q2W

Participants received INCAGN01876 3.0 mg/kg administered IV Q2W for a total of 2 doses as run-in, followed by nivolumab 240 mg administered IV Q2W starting at Cycle 3.

Phase 1 Group B: INCAGN01876 3.0 mg/kg Q2W, Then Nivolumab 240 mg Q2W

Participants received INCAGN01876 5.0 mg/kg administered IV Q2W for a total of 2 doses as run-in, followed by nivolumab 240 mg administered IV Q2W starting at Cycle 3.

Phase 1 Group B: INCAGN01876 5.0 mg/kg Q2W, Then Nivolumab 240 mg Q2W

Phase 1 Group C: INCAGN01876 1.0 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W

Phase 1 Group C: INCAGN01876 3.0 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W

Phase 1 Group C: INCAGN01876 5.0 mg/kg Q2W + Ipilimumab 1 mg/kg Q6W

Phase 1 Group D: INCAGN01876 + Nivolumab + Ipilimumab

Participants with programmed cell death protein/programmed cell death ligand 1 (PD-1/PD-L1) relapsed melanoma (RM) received INCAGN01876 300 mg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV Q6W.

Phase 2 Group C2 PD-1/PD-L1 RM: INCAGN01876 300 mg + Ipilimumab 1 mg/kg

Phase 2 Group F GC: INCAGN01876 300 mg + Nivolumab 240 mg

Phase 2 Group F SCCHN INCAGN01876 300 mg + Nivolumab 240 mg

Phase 2 Group F CC: INCAGN01876 300 mg + Nivolumab 240 mg

Phase 2 Group F PD-1/PD-L1 RM: INCAGN01876 300 mg + Nivolumab 240 mg

Phase 2 Group F Biopsy: INCAGN01876 300 mg + Nivolumab 240 mg

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

White/Caucasian

Black or African American

Asian

American Indian or Alaska Native

Native Hawaiin or Other Pacific Islander

Other: Captured as "Other"

Other: Zimbabwean

Other: Mexican

Race/Ethnicity, Customized

The full analysis set (FAS) included all participants enrolled in the study who received at least 1 dose of study drug.

Study Director

Participants received INCAGN01876 1.0 mg/kg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.

Phase 1 Group D: INCAGN01876 1.0 mg/kg + Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg

Phase 1 Full Analysis Set (FAS): all participants enrolled in Phase 1 of the study who received at least 1 dose of INCAGN01876, nivolumab, or ipilimumab

Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)

Phase 2 Response Evaluable Population: all participants enrolled in Phase 2 who received at least 1 dose of INCAGN01876, nivolumab, or ipilimumab; completed a Baseline scan; and met at least 1 of the following criteria: (a) ≥1 post-Baseline scan (b) the participant has been in the study for a minimum of 64 days of follow-up; or (c) the participant had discontinued from treatment

Phase 2: Objective Response Rate (ORR) Per RECIST v1.1

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.INCAGN01876 combined with nivolumab.

Phase 1 Response Evaluable Population: all participants enrolled in Phase 1 who received at least 1 dose of INCAGN01876, nivolumab, or ipilimumab; completed a Baseline scan; and met at least 1 of the following criteria: (a) ≥1 post-Baseline scan (b) the participant has been in the study for a minimum of 64 days of follow-up; or (c) the participant had discontinued from treatment

Phase 1: ORR Per RECIST v1.1

Phase 1: ORR Per Modified RECIST (mRECIST) v1.1

Phase 2: ORR Per mRECIST v1.1

Phase 1 Response Evaluable Population. Only those participants with a response of CR or PR were analyzed. The confidence interval for median survival time was calculated using the method of Brookmeyer and Crowley.

Phase 1: Duration of Response (DOR) Per RECIST v1.1

Phase 2 Group C2: PD-1/PD-L1 RM: INCAGN01876 300 mg + Ipilimumab 1 mg/kg

Phase 2 Group F: Biopsy: INCAGN01876 300 mg + Nivolumab 240 mg

Phase 2 Response Evaluable Population. Only those participants with a response of CR or PR were analyzed. The confidence interval for median survival time was calculated using the method of Brookmeyer and Crowley.

Phase 2: DOR Per RECIST v1.1

Phase 1: DOR Per mRECIST v1.1

Phase 2: DOR Per mRECIST v1.1

Phase 1: Disease Control Rate (DCR) Per RECIST v1.1

Phase 2: DCR Per RECIST v1.1

Phase 1: DCR Per mRECIST v1.1

Phase 2: DCR Per mRECIST v1.1

Phase 1 Response Evaluable Population. The confidence intervals was calculated based on the exact method for binomial distributions. Only those participants with a response of SD, CR, or PR were analyzed.

Phase 1: Duration of Disease Control Per RECIST v1.1

Phase 2 Response Evaluable Population. The confidence intervals was calculated based on the exact method for binomial distributions. Only those participants with a response of SD, CR, or PR were analyzed.

Phase 2: Duration of Disease Control Per RECIST v1.1

Phase 1: Duration of Disease Control Per mRECIST v1.1

Phase 2: Duration of Disease Control Per mRECIST v1.1

Phase 1 FAS. Median survival time was estimated using the Kaplan-Meier method. The confidence interval for median survival time was calculated using the method of Brookmeyer and Crowley.

Phase 1: Progression-free Survival (PFS) Per RECIST v1.1

Phase 2 FAS. Median survival time was estimated using the Kaplan-Meier method. The confidence interval for median survival time was calculated using the method of Brookmeyer and Crowley.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of INCAGN01876 Combined With Immune Therapies in Advanced or Metastatic Malignancies	NCT03126110	Advanced Malign... Metastatic Canc...	INCAGN01876 Nivolumab Ipilimumab	18 Years -	Incyte Corporation
Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of INCAGN01876 Combined With Immune Therapies in Advanced or Metastatic Malignancies	NCT03126110	Advanced Malign... Metastatic Canc...	INCAGN01876 Nivolumab Ipilimumab	18 Years -	Incyte Corporation

Spots Global Cancer Trial Database for gastric cancer (stomach, esophageal, and gastroesophageal junction [gej])