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

• ClinicalTrials.gov Identifier: NCT03126110
• Recruitment Status: Completed
• First Posted: April 24, 2017
• Results First Posted: December 28, 2022
• Last Update Posted: December 28, 2022
• Sponsor: Incyte Biosciences International Sàrl
• Information provided by (Responsible Party): Incyte Corporation ( Incyte Biosciences International Sàrl )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Advanced Malignancies; Metastatic Cancer	Drug: INCAGN01876; Drug: Nivolumab; Drug: Ipilimumab	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 145 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: April 25, 2017
• Actual Primary Completion Date: November 9, 2021
• Actual Study Completion Date: November 9, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Phase 1 Group A: INCAGN01876 1.0 mg/kg Q2W + nivolumab 240 mg Q2W; 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.	Drug: INCAGN01876; 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 ().; Drug: Nivolumab; Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.
Experimental: Phase 1 Group A: INCAGN01876 3.0 mg/kg Q2W + nivolumab 240 mg Q2W; Participants received INCAGN01876 3.0 mg/kg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.	Drug: INCAGN01876; 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 ().; Drug: Nivolumab; Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.
Experimental: Phase 1 Group A: INCAGN01876 5.0 mg/kg Q2W + nivolumab 240 mg Q2W; Participants received INCAGN01876 5.0 mg/kg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.	Drug: INCAGN01876; 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 ().; Drug: Nivolumab; Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.
Experimental: Phase 1 Group A: INCAGN01876 10.0 mg/kg Q2W + nivolumab 240 mg Q2W; Participants received INCAGN01876 10.0 mg/kg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.	Drug: INCAGN01876; 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 ().; Drug: Nivolumab; Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.
Experimental: Phase 1 Group B: INCAGN01876 1.0 mg/kg Q2W, then 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 INCAGN01876 1.0 mg/kg Q2W in combination with nivolumab 240 mg administered IV Q2W starting at Cycle 3.	Drug: INCAGN01876; 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 ().; Drug: Nivolumab; Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.
Experimental: Phase 1 Group B: INCAGN01876 3.0 mg/kg Q2W, then 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 INCAGN01876 1.0 mg/kg Q2W in combination with nivolumab 240 mg administered IV Q2W starting at Cycle 3.	Drug: INCAGN01876; 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 ().; Drug: Nivolumab; Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.
Experimental: Phase 1 Group B: INCAGN01876 5.0 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 INCAGN01876 5.0 mg/kg Q2W in combination with nivolumab 240 mg administered IV Q2W starting at Cycle 3.	Drug: INCAGN01876; 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 ().; Drug: Nivolumab; Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.
Experimental: Phase 1 Group C: INCAGN01876 1.0 mg/kg Q2W + ipilimumab 1 mg/kg Q6W; Participants received INCAGN01876 1.0 mg/kg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV every 6 weeks (Q6W).	Drug: INCAGN01876; 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 ().; Drug: Ipilimumab; Ipilimumab will be administered IV at the protocol-defined dose according to assigned treatment group.
Experimental: Phase 1 Group C: INCAGN01876 3.0 mg/kg Q2W + ipilimumab 1 mg/kg Q6W; Participants received INCAGN01876 3.0 mg/kg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV Q6W.	Drug: INCAGN01876; 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 ().; Drug: Ipilimumab; Ipilimumab will be administered IV at the protocol-defined dose according to assigned treatment group.
Experimental: Phase 1 Group C: INCAGN01876 5.0 mg/kg Q2W + ipilimumab 1 mg/kg Q6W; Participants received INCAGN01876 5.0 mg/kg administered IV Q2W in combination with ipilimumab 1 mg/kg administered IV Q6W.	Drug: INCAGN01876; 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 ().; Drug: Ipilimumab; Ipilimumab will be administered IV at the protocol-defined dose according to assigned treatment group.
Experimental: Phase 1 Group D: INCAGN01876 + Nivolumab + Ipilimumab; 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.	Drug: INCAGN01876; 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 ().; Drug: Nivolumab; Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.; Drug: Ipilimumab; Ipilimumab will be administered IV at the protocol-defined dose according to assigned treatment group.
Experimental: Phase 2 Group C2 PD-1/PD-L1: INCAGN01876 300 mg + ipilimumab 1 mg/kg; 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.	Drug: INCAGN01876; 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 ().; Drug: Ipilimumab; Ipilimumab will be administered IV at the protocol-defined dose according to assigned treatment group.
Experimental: Phase 2 Group F GC: INCAGN01876 300 mg + nivolumab 240 mg; Participants with gastric cancer (GC) received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.	Drug: INCAGN01876; 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 ().; Drug: Nivolumab; Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.
Experimental: Phase 2 Group F SCCHN INCAGN01876 300 mg + nivolumab 240 mg; 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.	Drug: INCAGN01876; 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 ().; Drug: Nivolumab; Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.
Experimental: Phase 2 Group F CC: INCAGN01876 300 mg + nivolumab 240 mg; Participants with cervical cancer (CC) received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.	Drug: INCAGN01876; 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 ().; Drug: Nivolumab; Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.
Experimental: Phase 2 Group F PD-1/PD-L1: INCAGN01876 300 mg + nivolumab 240 mg; Participants with PD-1/PD-L1 relapsed melanoma received INCAGN01876 300 mg administered IV Q2W in combination with nivolumab 240 mg administered IV Q2W.	Drug: INCAGN01876; 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 ().; Drug: Nivolumab; Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.
Experimental: Phase 2 Group F Biopsy: INCAGN01876 300 mg + nivolumab 240 mg; 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.	Drug: INCAGN01876; 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 ().; Drug: Nivolumab; Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.

Outcome Measures

Primary Outcome Measures :

1. Phase 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) [ Time Frame: up to approximately 27.4 months ]
   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.
2. Phase 2: Objective Response Rate (ORR) Per RECIST v1.1 [ Time Frame: up to approximately 44.7 months ]
   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.

Secondary Outcome Measures :

1. Phase 1: ORR Per RECIST v1.1 [ Time Frame: up to approximately 44.7 months ]
   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.
2. Phase 1: ORR Per Modified RECIST (mRECIST) v1.1 [ Time Frame: up to approximately 44.7 months ]
   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.
3. Phase 2: ORR Per mRECIST v1.1 [ Time Frame: up to approximately 44.7 months ]
   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.
4. Phase 1: Duration of Response (DOR) Per RECIST v1.1 [ Time Frame: up to approximately 44.7 months ]
   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.
5. Phase 2: DOR Per RECIST v1.1 [ Time Frame: up to approximately 44.7 months ]
   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.
6. Phase 1: DOR Per mRECIST v1.1 [ Time Frame: up to approximately 44.7 months ]
   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.
7. Phase 2: DOR Per mRECIST v1.1 [ Time Frame: up to approximately 44.7 months ]
   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.
8. Phase 1: Disease Control Rate (DCR) Per RECIST v1.1 [ Time Frame: up to approximately 44.7 months ]
   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.
9. Phase 2: DCR Per RECIST v1.1 [ Time Frame: up to approximately 44.7 months ]
   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.
10. Phase 1: DCR Per mRECIST v1.1 [ Time Frame: up to approximately 44.7 months ]
    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.
11. Phase 2: DCR Per mRECIST v1.1 [ Time Frame: up to approximately 44.7 months ]
    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.
12. Phase 1: Duration of Disease Control Per RECIST v1.1 [ Time Frame: up to approximately 44.7 months ]
    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.
13. Phase 2: Duration of Disease Control Per RECIST v1.1 [ Time Frame: up to approximately 44.7 months ]
    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.
14. Phase 1: Duration of Disease Control Per mRECIST v1.1 [ Time Frame: up to approximately 44.7 months ]
    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.
15. Phase 2: Duration of Disease Control Per mRECIST v1.1 [ Time Frame: up to approximately 44.7 months ]
    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. [
16. Phase 1: Progression-free Survival (PFS) Per RECIST v1.1 [ Time Frame: up to approximately 44.7 months ]
    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.
17. Phase 2: PFS Per RECIST v1.1 [ Time Frame: up to approximately 44.7 months ]
    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.
18. Phase 1: PFS Per mRECIST v1.1 [ Time Frame: up to approximately 44.7 months ]
    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).
19. Phase 2: PFS Per mRECIST v1.1 [ Time Frame: up to approximately 44.7 months ]
    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).
20. Phase 1: Overall Survival [ Time Frame: up to approximately 44.7 months ]
    Overall survival was defined as the interval between the Baseline visit (Day 1) and the date of death due to any cause.
21. Phase 2: Overall Survival [ Time Frame: up to approximately 44.7 months ]
    Overall survival was defined as the interval between the Baseline visit (Day 1) and the date of death due to any cause.
22. Phase 2: : Number of Participants With Any TEAE [ Time Frame: up to approximately 27.4 months ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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 solid tumors.
• Phase 1: Subjects who have disease progression after treatment with available therapies.
• Phase 2: Subjects with advanced or metastatic cervical cancer, gastric cancer (including stomach, esophageal, and GEJ), SCCHN, PD-1 refractory SCCHN and PD-1/PD-L1 relapsed melanoma.
• Presence of measurable disease based on RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.

Exclusion Criteria:

• Laboratory and medical history parameters not within the Protocol-defined range
• Prior treatment with any tumor necrosis factor super family agonist.
• Receipt of anticancer medications or investigational drugs within protocol-defined intervals before the first administration of study drug.
• Has not recovered to ≤ Grade 1 from toxic effects of prior therapy.
• Active autoimmune disease.
• Known active central nervous system metastases and/or carcinomatous meningitis.
• Evidence of active, noninfectious pneumonitis or history of interstitial lung disease.
• 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).

Contacts and Locations

Locations

United States, California

The Angeles Clinic and Research Institute

Los Angeles, California, United States, 90025

United States, Florida

University of Florida

Gainesville, Florida, United States, 32610

United States, Michigan

Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

United States, Missouri

Washington University - Siteman Cancer Center

Saint Louis, Missouri, United States, 37201

United States, New Jersey

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

United States, New York

Memorial Sloan Kettering Cancer

New York, New York, United States, 10065

United States, North Carolina

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States, 27599

United States, Oklahoma

University of Oklahoma, Sarah Cannon Research Institute

Oklahoma City, Oklahoma, United States, 73104

United States, Oregon

Providance Portland Medical Center

Portland, Oregon, United States, 97213

United States, Pennsylvania

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

University of Pittsburgh, UPMC Cancer Pavilion

Pittsburgh, Pennsylvania, United States, 15232

United States, Tennessee

Tennessee Oncology, Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37201

United States, Texas

BUMC Mary Crowley Cancer Research Centers

Dallas, Texas, United States, 75230

MD Anderson

Houston, Texas, United States, 77030

United States, Washington

Seattle Cancer Care Alliance

Seattle, Washington, United States, 98109

Australia, New South Wales

Blacktown Cancer and Haematology Centre

Blacktown, New South Wales, Australia, 2148

Scientia Clinical Research

Randwick, New South Wales, Australia, 2148

Australia, Queensland

Greenslopes Private Hospital

Brisbane, Queensland, Australia, 4120

Australia, Victoria

Austin Hospital

Heidelberg, Victoria, Australia, 3084

Australia, Western Australia

Linear Clinical Research

Perth, Western Australia, Australia, 6009

Belgium

CHA Centre Hospitalier de l'Ardenne

Libramont, Chevigny, Belgium, 6800

Saint Augustinus Hospital

Antwerpen, Belgium, 2610

Institut Jules Bordet

Brussels, Belgium, 1000

Cliniques Universitaires Saint-Luc

Brussels, Belgium, 1200

CHU Brugmann

Bruxelles, Belgium, 1020

Mi Kryviy Rih Center of Dnipropetrovsk Regional Council

Charleroi, Belgium, 6000

Ghent University Hospital

Ghent, Belgium, 37201

AZ Groeninge

Kortrijk, Belgium, 8500

Spain

Hospital Clinic I Provincial

Barcelona, Spain, 08036

Hospital Clinico y Provincial de Barcelona

Barcelona, Spain, 08036

Institut Catala D'Oncologia-Badalona

Barcelona, Spain, 08916

Hospital Vall de Hebron

Barcelona, Spain

Hospital Reina Sophia

Córdoba, Spain, 14004

University Hospital Ramon y Cajal

Madrid, Spain, 28034

Hospital Universitario Doce de Octubre

Madrid, Spain, 28041

Hospital HM Sanchinarro

Madrid, Spain, 28050

Clinica Universidad De Navarra (CUN)

Pamplona, Spain, 31008

Hospital Universitario Virgen Del Rocio

Sevilla, Spain, 41015

Sponsors and Collaborators

Incyte Biosciences International Sàrl

Investigators

• Study Director: John E. Janik, MD; Incyte Corporation

  Study Documents (Full-Text)

Documents provided by Incyte Corporation ( Incyte Biosciences International Sàrl ):

Study Protocol  [PDF] January 22, 2021

Statistical Analysis Plan  [PDF] December 5, 2017

More Information

• Responsible Party: Incyte Biosciences International Sàrl
• ClinicalTrials.gov Identifier: NCT03126110
• Other Study ID Numbers: INCAGN 1876-201
• First Posted: April 24, 2017
• Results First Posted: December 28, 2022
• Last Update Posted: December 28, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Incyte Corporation ( Incyte Biosciences International Sàrl ):

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)

Additional relevant MeSH terms:

Neoplasms; Nivolumab; Ipilimumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action