Advanced Malignancies
Conditions
Keywords
advanced or metastatic cervical cancer, endometrial cancer, esophageal cancer, hepatocellular carcinoma (HCC), melanoma, Merkel cell carcinoma, mesothelioma, microsatellite instability-high colorectal cancer, non-small cell lung cancer (NSCLC), ovarian cancer, squamous cell carcinoma of the head and neck, small cell lung cancer (SLCL), renal cell carcinoma (RCC), triple-negative breast cancer, TNBC, urothelial carcinoma, OX40 ligand (OX40), SCCHN, MSI-H CRC, gastric cancer (including stomach and gastroesophageal junction [GEJ])
Brief summary
The purpose of this study is to determine the safety, tolerability, and efficacy of INCAGN01949 when given in combination with immune therapies in participants with advanced or metastatic malignancies.
Interventions
DRUGINCAGN01949
In Phase 1, participants will receive INCAGN01949 administered intravenously (IV) at the protocol-defined dose according to cohort enrollment. In Phase 2, participants will receive INCAGN01949 administered IV at the recommended dose from Phase 1.
DRUGNivolumab
Nivolumab will be administered IV at the protocol-defined dose according to assigned treatment group.
DRUGIpilimumab
Ipilimumab will be administered IV at the protocol-defined dose according to assigned treatment group.
Sponsors
Incyte Biosciences International Sàrl
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 gastric cancer, SCCHN, NSCLC, or RCC and are considered refractory to prior PD-1/L1 therapy. * 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 * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | up to 17.4 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 that occurred 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 adverse event either reported for the first time or the worsening of a pre-existing event after the first dose of study drug. |
| Phase 1: Number of Participants With a Grade 3 or Higher TEAE | up to 17.4 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. A TEAE was defined as any adverse event either reported for the first time or the worsening of a pre-existing event after the first dose of study drug. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.03. 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. |
| Phase 2: Objective Response Rate (ORR) | up to 24 months | ORR was defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1), as determined by investigator assessment of radiographic disease assessments, recorded before and including the first event of progressive disease (PD). 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
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Disease Control Rate (DCR) | up to 15.6 months | DCR was defined as the percentage of participants with a CR, PR, or stable disease (SD), 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. SD: no change in target lesions to qualify for CR, PR, or PD. |
| Phase 2: DCR | up to 24 months | DCR was defined as the percentage of participants with a CR, PR, or SD, 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. SD: no change in target lesions to qualify for CR, PR, or PD. |
| Phase 1: Duration of Disease Control | up to 15.4 months | Duration of disease control (CR, PR, and SD) was measured from the first report of SD or better until PD or death from any cause, if occurring sooner than progression, 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. SD: no change in target lesions to qualify for CR, PR, or PD. PD: progression of a target or non-target lesion or presence of a new lesion. |
| Phase 2: Duration of Disease Control | up to 24 months | Duration of disease control (CR, PR, and SD) was measured from the first report of SD or better until PD or death from any cause, if occurring sooner than progression, 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. SD: no change in target lesions to qualify for CR, PR, or PD. PD: progression of a target or non-target lesion or presence of a new lesion. |
| Phase 1: ORR | up to 15.6 months | ORR was defined as the percentage of participants with a confirmed best overall response of CR or PR, per RECIST v1.1, as determined by investigator assessment of radiographic disease assessments, recorded before and including the first event of PD. 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. |
| Phase 2: PFS | up to 24 months | 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 per RECIST v1.1. |
| Phase 2: Number of Participants With TEAEs | up to 24 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 that occurred 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 adverse event either reported for the first time or the worsening of a pre-existing event after the first dose of study drug. |
| Phase 2: Number of Participants With a Grade 3 or Higher TEAE | up to 24 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. A TEAE was defined as any adverse event either reported for the first time or the worsening of a pre-existing event after the first dose of study drug. The severity of AEs was assessed using CTCAE v4.03. 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. |
| Phase 1: Progression-free Survival (PFS) | up to 15.6 months | 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 per RECIST v1.1. |
| Phase 1: Duration of Response (DOR) | up to 11.0 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 first assessment of PD, 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. |
| Phase 2: DOR | up to 24 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 first assessment of PD, 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. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at 13 study centers in the United States in two parts: dose escalation (Part 1) and safety expansion (Part 2).
Participants by arm
| Arm | Count |
|---|---|
| Phase 1, Dose Escalation: INCAGN01949 70 mg + Nivolumab 240 mg Participants with advanced or metastatic select solid tumors received INCAGN01949 70 milligrams (mg) every 2 weeks (Q2W) beginning on Cycle 1 Day 1, followed by nivolumab 240 mg Q2W beginning on Cycle 1 Day 1, administered as intravenous (IV) infusions. | 4 |
| Phase 1, Dose Escalation: INCAGN01949 200 mg + Nivolumab 240 mg Participants with advanced or metastatic select solid tumors received INCAGN01949 200 mg Q2W beginning on Cycle 1 Day 1, followed by nivolumab 240 mg Q2W beginning on Cycle 1 Day 1, administered as IV infusions. | 4 |
| Phase 1, Dose Escalation: INCAGN01949 350 mg + Nivolumab 240 mg Participants with advanced or metastatic select solid tumors received INCAGN01949 350 mg Q2W beginning on Cycle 1 Day 1, followed by nivolumab 240 mg Q2W beginning on Cycle 1 Day 1, administered as IV infusions. | 5 |
| Phase 1, Dose Escalation: INCAGN01949 700 mg + Nivolumab 240 mg Participants with advanced or metastatic select solid tumors received INCAGN01949 700 mg Q2W beginning on Cycle 1 Day 1, followed by nivolumab 240 mg Q2W beginning on Cycle 1 Day 1, administered as IV infusions. | 5 |
| Phase 1, Dose Escalation: INCAGN01949 70 mg + Ipilimumab 1 mg/kg Participants with advanced or metastatic select solid tumors received INCAGN01949 70 mg Q2W beginning on Cycle 1 Day 1, followed by ipilimumab 1 mg/kilogram (kg) every 6 weeks (Q6W) beginning on Cycle 1 Day 1, administered as IV infusions. | 4 |
| Phase 1, Dose Escalation: INCAGN01949 200 mg + Ipilimumab 1 mg/kg Participants with advanced or metastatic select solid tumors received INCAGN01949 200 mg Q2W beginning on Cycle 1 Day 1, followed by ipilimumab 1 mg/kg Q6W beginning on Cycle 1 Day 1, administered as IV infusions. | 5 |
| Phase 1, Dose Escalation: INCAGN01949 350 mg + Ipilimumab 1 mg/kg Participants with advanced or metastatic select solid tumors received INCAGN01949 350 mg Q2W beginning on Cycle 1 Day 1, followed by ipilimumab 1 mg/kg Q6W beginning on Cycle 1 Day 1, administered as IV infusions. | 4 |
| Phase 1, Dose Escalation: INCAGN01949 700 mg + Ipilimumab 1 mg/kg Participants with advanced or metastatic select solid tumors received INCAGN01949 700 mg Q2W beginning on Cycle 1 Day 1, followed by ipilimumab 1 mg/kg Q6W beginning on Cycle 1 Day 1, administered as IV infusions. | 3 |
| Phase 1, Safety Expansion: INCAGN01949 70 mg + Nivolumab 240 mg Participants with advanced or metastatic select solid tumors received INCAGN01949 70 mg Q2W beginning on Cycle 1 Day 1, followed by nivolumab 240 mg Q2W beginning on Cycle 3 Day 1, administered as IV infusions. | 6 |
| Phase 1, Safety Expansion: INCAGN01949 200 mg + Nivolumab 240 mg Participants with advanced or metastatic select solid tumors received INCAGN01949 200 mg Q2W beginning on Cycle 1 Day 1, followed by nivolumab 240 mg Q2W beginning on Cycle 3 Day 1, administered as IV infusions. | 6 |
| Phase 1, Safety Expansion: INCAGN01949 350 mg + Nivolumab 240 mg Participants with advanced or metastatic select solid tumors received INCAGN01949 350 mg Q2W beginning on Cycle 1 Day 1, followed by nivolumab 240 mg Q2W beginning on Cycle 3 Day 1, administered as IV infusions. | 6 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 3 | 2 | 4 | 4 | 2 | 2 | 3 | 1 | 0 | 5 | 4 | 3 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Survival Follow-up No Longer Required per Protocol Amendment | 1 | 2 | 0 | 1 | 1 | 2 | 1 | 2 | 0 | 0 | 2 | 3 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Phase 1, Dose Escalation: INCAGN01949 70 mg + Nivolumab 240 mg | Phase 1, Dose Escalation: INCAGN01949 200 mg + Nivolumab 240 mg | Phase 1, Dose Escalation: INCAGN01949 350 mg + Nivolumab 240 mg | Phase 1, Dose Escalation: INCAGN01949 700 mg + Nivolumab 240 mg | Phase 1, Dose Escalation: INCAGN01949 70 mg + Ipilimumab 1 mg/kg | Phase 1, Dose Escalation: INCAGN01949 200 mg + Ipilimumab 1 mg/kg | Phase 1, Dose Escalation: INCAGN01949 350 mg + Ipilimumab 1 mg/kg | Phase 1, Dose Escalation: INCAGN01949 700 mg + Ipilimumab 1 mg/kg | Phase 1, Safety Expansion: INCAGN01949 70 mg + Nivolumab 240 mg | Phase 1, Safety Expansion: INCAGN01949 200 mg + Nivolumab 240 mg | Phase 1, Safety Expansion: INCAGN01949 350 mg + Nivolumab 240 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 45.0 years STANDARD_DEVIATION 7.53 | 58.0 years STANDARD_DEVIATION 3.16 | 60.0 years STANDARD_DEVIATION 5 | 67.8 years STANDARD_DEVIATION 8.07 | 58.5 years STANDARD_DEVIATION 6.45 | 60.6 years STANDARD_DEVIATION 10.21 | 59.3 years STANDARD_DEVIATION 12.71 | 50.0 years STANDARD_DEVIATION 20.52 | 60.5 years STANDARD_DEVIATION 8.73 | 55.7 years STANDARD_DEVIATION 15.96 | 64.0 years STANDARD_DEVIATION 13.96 | 58.77 years STANDARD_DEVIATION 11.48 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 3 Participants | 4 Participants | 4 Participants | 3 Participants | 6 Participants | 6 Participants | 6 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 4 Participants | 4 Participants | 4 Participants | 5 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 5 Participants | 6 Participants | 5 Participants | 44 Participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 3 Participants | 1 Participants | 6 Participants | 3 Participants | 2 Participants | 26 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants | 4 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 4 | 2 / 4 | 4 / 5 | 4 / 5 | 2 / 4 | 2 / 5 | 3 / 4 | 1 / 3 | 5 / 6 | 4 / 6 | 3 / 6 | 33 / 52 |
| other Total, other adverse events | 4 / 4 | 4 / 4 | 5 / 5 | 5 / 5 | 4 / 4 | 5 / 5 | 4 / 4 | 3 / 3 | 6 / 6 | 6 / 6 | 6 / 6 | 52 / 52 |
| serious Total, serious adverse events | 3 / 4 | 1 / 4 | 4 / 5 | 3 / 5 | 2 / 4 | 2 / 5 | 2 / 4 | 1 / 3 | 4 / 6 | 3 / 6 | 3 / 6 | 28 / 52 |
Outcome results
Primary
Phase 1: Number of Participants With a Grade 3 or Higher TEAE
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. A TEAE was defined as any adverse event either reported for the first time or the worsening of a pre-existing event after the first dose of study drug. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.03. 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.
Time frame: up to 17.4 months
Population: FAS
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1, Dose Escalation: INCAGN01949 70 mg + Nivolumab 240 mg | Phase 1: Number of Participants With a Grade 3 or Higher TEAE | 2 Participants |
| Phase 1, Dose Escalation: INCAGN01949 200 mg + Nivolumab 240 mg | Phase 1: Number of Participants With a Grade 3 or Higher TEAE | 1 Participants |
| Phase 1, Dose Escalation: INCAGN01949 350 mg + Nivolumab 240 mg | Phase 1: Number of Participants With a Grade 3 or Higher TEAE | 3 Participants |
| Phase 1, Dose Escalation: INCAGN01949 700 mg + Nivolumab 240 mg | Phase 1: Number of Participants With a Grade 3 or Higher TEAE | 3 Participants |
| Phase 1, Dose Escalation: INCAGN01949 70 mg + Ipilimumab 1 mg/kg | Phase 1: Number of Participants With a Grade 3 or Higher TEAE | 2 Participants |
| Phase 1, Dose Escalation: INCAGN01949 200 mg + Ipilimumab 1 mg/kg | Phase 1: Number of Participants With a Grade 3 or Higher TEAE | 2 Participants |
| Phase 1, Dose Escalation: INCAGN01949 350 mg + Ipilimumab 1 mg/kg | Phase 1: Number of Participants With a Grade 3 or Higher TEAE | 3 Participants |
| Phase 1, Dose Escalation: INCAGN01949 700 mg + Ipilimumab 1 mg/kg | Phase 1: Number of Participants With a Grade 3 or Higher TEAE | 1 Participants |
| Phase 1, Safety Expansion: INCAGN01949 70 mg + Nivolumab 240 mg | Phase 1: Number of Participants With a Grade 3 or Higher TEAE | 5 Participants |
| Phase 1, Safety Expansion: INCAGN01949 200 mg + Nivolumab 240 mg | Phase 1: Number of Participants With a Grade 3 or Higher TEAE | 4 Participants |
| Phase 1, Safety Expansion: INCAGN01949 350 mg + Nivolumab 240 mg | Phase 1: Number of Participants With a Grade 3 or Higher TEAE | 3 Participants |
Primary
Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
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 that occurred 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 adverse event either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.
Time frame: up to 17.4 months
Population: Full Analysis Set (FAS): all participants enrolled in the study who received ≥ 1 dose of INCAGN01949, nivolumab, or ipilimumab
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1, Dose Escalation: INCAGN01949 70 mg + Nivolumab 240 mg | Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| Phase 1, Dose Escalation: INCAGN01949 200 mg + Nivolumab 240 mg | Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| Phase 1, Dose Escalation: INCAGN01949 350 mg + Nivolumab 240 mg | Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 5 Participants |
| Phase 1, Dose Escalation: INCAGN01949 700 mg + Nivolumab 240 mg | Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 5 Participants |
| Phase 1, Dose Escalation: INCAGN01949 70 mg + Ipilimumab 1 mg/kg | Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| Phase 1, Dose Escalation: INCAGN01949 200 mg + Ipilimumab 1 mg/kg | Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 5 Participants |
| Phase 1, Dose Escalation: INCAGN01949 350 mg + Ipilimumab 1 mg/kg | Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| Phase 1, Dose Escalation: INCAGN01949 700 mg + Ipilimumab 1 mg/kg | Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 3 Participants |
| Phase 1, Safety Expansion: INCAGN01949 70 mg + Nivolumab 240 mg | Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 Participants |
| Phase 1, Safety Expansion: INCAGN01949 200 mg + Nivolumab 240 mg | Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 Participants |
| Phase 1, Safety Expansion: INCAGN01949 350 mg + Nivolumab 240 mg | Phase 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 6 Participants |
Primary
Phase 2: Objective Response Rate (ORR)
ORR was defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1), as determined by investigator assessment of radiographic disease assessments, recorded before and including the first event of progressive disease (PD). 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.
Time frame: up to 24 months
Population: Phase 2 of the study did not open for enrollment.
Secondary
Phase 1: Disease Control Rate (DCR)
DCR was defined as the percentage of participants with a CR, PR, or stable disease (SD), 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. SD: no change in target lesions to qualify for CR, PR, or PD.
Time frame: up to 15.6 months
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1, Dose Escalation: INCAGN01949 70 mg + Nivolumab 240 mg | Phase 1: Disease Control Rate (DCR) | 25.0 percentage of participants |
| Phase 1, Dose Escalation: INCAGN01949 200 mg + Nivolumab 240 mg | Phase 1: Disease Control Rate (DCR) | 25.0 percentage of participants |
| Phase 1, Dose Escalation: INCAGN01949 350 mg + Nivolumab 240 mg | Phase 1: Disease Control Rate (DCR) | 40.0 percentage of participants |
| Phase 1, Dose Escalation: INCAGN01949 700 mg + Nivolumab 240 mg | Phase 1: Disease Control Rate (DCR) | 0.0 percentage of participants |
| Phase 1, Dose Escalation: INCAGN01949 70 mg + Ipilimumab 1 mg/kg | Phase 1: Disease Control Rate (DCR) | 75.0 percentage of participants |
| Phase 1, Dose Escalation: INCAGN01949 200 mg + Ipilimumab 1 mg/kg | Phase 1: Disease Control Rate (DCR) | 0.0 percentage of participants |
| Phase 1, Dose Escalation: INCAGN01949 350 mg + Ipilimumab 1 mg/kg | Phase 1: Disease Control Rate (DCR) | 50.0 percentage of participants |
| Phase 1, Dose Escalation: INCAGN01949 700 mg + Ipilimumab 1 mg/kg | Phase 1: Disease Control Rate (DCR) | 33.3 percentage of participants |
| Phase 1, Safety Expansion: INCAGN01949 70 mg + Nivolumab 240 mg | Phase 1: Disease Control Rate (DCR) | 33.3 percentage of participants |
| Phase 1, Safety Expansion: INCAGN01949 200 mg + Nivolumab 240 mg | Phase 1: Disease Control Rate (DCR) | 33.3 percentage of participants |
| Phase 1, Safety Expansion: INCAGN01949 350 mg + Nivolumab 240 mg | Phase 1: Disease Control Rate (DCR) | 66.7 percentage of participants |
Secondary
Phase 1: Duration of Disease Control
Duration of disease control (CR, PR, and SD) was measured from the first report of SD or better until PD or death from any cause, if occurring sooner than progression, 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. SD: no change in target lesions to qualify for CR, PR, or PD. PD: progression of a target or non-target lesion or presence of a new lesion.
Time frame: up to 15.4 months
Population: FAS. The confidence interval was calculated based on the exact method for binomial distributions. Only participants with a confirmed CR, PR, or SD were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1, Dose Escalation: INCAGN01949 70 mg + Nivolumab 240 mg | Phase 1: Duration of Disease Control | 97.0 days |
| Phase 1, Dose Escalation: INCAGN01949 200 mg + Nivolumab 240 mg | Phase 1: Duration of Disease Control | NA days |
| Phase 1, Dose Escalation: INCAGN01949 350 mg + Nivolumab 240 mg | Phase 1: Duration of Disease Control | 120.0 days |
| Phase 1, Dose Escalation: INCAGN01949 70 mg + Ipilimumab 1 mg/kg | Phase 1: Duration of Disease Control | 58.0 days |
| Phase 1, Dose Escalation: INCAGN01949 350 mg + Ipilimumab 1 mg/kg | Phase 1: Duration of Disease Control | 298.5 days |
| Phase 1, Dose Escalation: INCAGN01949 700 mg + Ipilimumab 1 mg/kg | Phase 1: Duration of Disease Control | 100.0 days |
| Phase 1, Safety Expansion: INCAGN01949 70 mg + Nivolumab 240 mg | Phase 1: Duration of Disease Control | 252.0 days |
| Phase 1, Safety Expansion: INCAGN01949 200 mg + Nivolumab 240 mg | Phase 1: Duration of Disease Control | 117.0 days |
| Phase 1, Safety Expansion: INCAGN01949 350 mg + Nivolumab 240 mg | Phase 1: Duration of Disease Control | 115.0 days |
Secondary
Phase 1: Duration of Response (DOR)
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 first assessment of PD, 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.
Time frame: up to 11.0 months
Population: FAS. The confidence interval was calculated using the method of Brookmeyer and Crowley. Only participants with a confirmed CR or PR were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1, Dose Escalation: INCAGN01949 70 mg + Nivolumab 240 mg | Phase 1: Duration of Response (DOR) | 97.0 days |
| Phase 1, Dose Escalation: INCAGN01949 200 mg + Nivolumab 240 mg | Phase 1: Duration of Response (DOR) | NA days |
| Phase 1, Safety Expansion: INCAGN01949 200 mg + Nivolumab 240 mg | Phase 1: Duration of Response (DOR) | 86.0 days |
Secondary
Phase 1: ORR
ORR was defined as the percentage of participants with a confirmed best overall response of CR or PR, per RECIST v1.1, as determined by investigator assessment of radiographic disease assessments, recorded before and including the first event of PD. 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.
Time frame: up to 15.6 months
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1, Dose Escalation: INCAGN01949 70 mg + Nivolumab 240 mg | Phase 1: ORR | 25.0 percentage of participants |
| Phase 1, Dose Escalation: INCAGN01949 200 mg + Nivolumab 240 mg | Phase 1: ORR | 25.0 percentage of participants |
| Phase 1, Dose Escalation: INCAGN01949 350 mg + Nivolumab 240 mg | Phase 1: ORR | 0.0 percentage of participants |
| Phase 1, Dose Escalation: INCAGN01949 700 mg + Nivolumab 240 mg | Phase 1: ORR | 0.0 percentage of participants |
| Phase 1, Dose Escalation: INCAGN01949 70 mg + Ipilimumab 1 mg/kg | Phase 1: ORR | 0.0 percentage of participants |
| Phase 1, Dose Escalation: INCAGN01949 200 mg + Ipilimumab 1 mg/kg | Phase 1: ORR | 0.0 percentage of participants |
| Phase 1, Dose Escalation: INCAGN01949 350 mg + Ipilimumab 1 mg/kg | Phase 1: ORR | 0.0 percentage of participants |
| Phase 1, Dose Escalation: INCAGN01949 700 mg + Ipilimumab 1 mg/kg | Phase 1: ORR | 0.0 percentage of participants |
| Phase 1, Safety Expansion: INCAGN01949 70 mg + Nivolumab 240 mg | Phase 1: ORR | 0.0 percentage of participants |
| Phase 1, Safety Expansion: INCAGN01949 200 mg + Nivolumab 240 mg | Phase 1: ORR | 16.7 percentage of participants |
| Phase 1, Safety Expansion: INCAGN01949 350 mg + Nivolumab 240 mg | Phase 1: ORR | 0.0 percentage of participants |
Secondary
Phase 1: Progression-free Survival (PFS)
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 per RECIST v1.1.
Time frame: up to 15.6 months
Population: FAS. Median survival time was estimated using the Kaplan-Meier method. The confidence interval was calculated using the method of Brookmeyer and Crowley. Only participants with events of disease progression or death were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1, Dose Escalation: INCAGN01949 70 mg + Nivolumab 240 mg | Phase 1: Progression-free Survival (PFS) | 1.8 days |
| Phase 1, Dose Escalation: INCAGN01949 200 mg + Nivolumab 240 mg | Phase 1: Progression-free Survival (PFS) | 1.8 days |
| Phase 1, Dose Escalation: INCAGN01949 350 mg + Nivolumab 240 mg | Phase 1: Progression-free Survival (PFS) | 2.7 days |
| Phase 1, Dose Escalation: INCAGN01949 700 mg + Nivolumab 240 mg | Phase 1: Progression-free Survival (PFS) | 1.8 days |
| Phase 1, Dose Escalation: INCAGN01949 70 mg + Ipilimumab 1 mg/kg | Phase 1: Progression-free Survival (PFS) | 3.5 days |
| Phase 1, Dose Escalation: INCAGN01949 200 mg + Ipilimumab 1 mg/kg | Phase 1: Progression-free Survival (PFS) | 1.6 days |
| Phase 1, Dose Escalation: INCAGN01949 350 mg + Ipilimumab 1 mg/kg | Phase 1: Progression-free Survival (PFS) | 4.6 days |
| Phase 1, Dose Escalation: INCAGN01949 700 mg + Ipilimumab 1 mg/kg | Phase 1: Progression-free Survival (PFS) | 1.8 days |
| Phase 1, Safety Expansion: INCAGN01949 70 mg + Nivolumab 240 mg | Phase 1: Progression-free Survival (PFS) | 1.6 days |
| Phase 1, Safety Expansion: INCAGN01949 200 mg + Nivolumab 240 mg | Phase 1: Progression-free Survival (PFS) | 2.2 days |
| Phase 1, Safety Expansion: INCAGN01949 350 mg + Nivolumab 240 mg | Phase 1: Progression-free Survival (PFS) | 4.6 days |
Secondary
Phase 2: DCR
DCR was defined as the percentage of participants with a CR, PR, or SD, 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. SD: no change in target lesions to qualify for CR, PR, or PD.
Time frame: up to 24 months
Population: Phase 2 of the study did not open for enrollment.
Secondary
Phase 2: DOR
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 first assessment of PD, 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.
Time frame: up to 24 months
Population: Phase 2 of the study did not open for enrollment.
Secondary
Phase 2: Duration of Disease Control
Duration of disease control (CR, PR, and SD) was measured from the first report of SD or better until PD or death from any cause, if occurring sooner than progression, 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. SD: no change in target lesions to qualify for CR, PR, or PD. PD: progression of a target or non-target lesion or presence of a new lesion.
Time frame: up to 24 months
Population: Phase 2 of the study did not open for enrollment.
Secondary
Phase 2: Number of Participants With a Grade 3 or Higher TEAE
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. A TEAE was defined as any adverse event either reported for the first time or the worsening of a pre-existing event after the first dose of study drug. The severity of AEs was assessed using CTCAE v4.03. 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.
Time frame: up to 24 months
Population: Phase 2 of the study did not open for enrollment.
Secondary
Phase 2: Number of Participants With TEAEs
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 that occurred 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 adverse event either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.
Time frame: up to 24 months
Population: Phase 2 of the study did not open for enrollment.
Secondary
Phase 2: PFS
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 per RECIST v1.1.
Time frame: up to 24 months
Population: Phase 2 of the study did not open for enrollment.