B-cell Malignancies, Colorectal Cancer (CRC), Glioblastoma, Head and Neck Cancer, Lung Cancer, Lymphoma, Melanoma, Ovarian Cancer
Conditions
Brief summary
This is a Phase 1/2, open label study. Phase 1 consists of 2 parts. Part 1 is a dose-escalation assessment of the safety and tolerability of epacadostat administered with nivolumab in subjects with select advanced solid tumors and lymphomas. Part 2 will evaluate the safety and tolerability of epacadostat in combination with nivolumab and chemotherapy in subjects with squamous cell carcinoma of head and neck (SCCHN) and non-small cell lung cancer (NSCLC). Phase 2 will include expansion cohorts in 7 tumor types, including melanoma, NSCLC, SCCHN, colorectal cancer, ovarian cancer, glioblastoma and diffuse large B-cell lymphoma (DLBCL).
Interventions
DRUGNivolumab
specified dose and dosing schedule
DRUGEpacadostat
oral twice daily continuous at the protocol-defined dose
DRUGChemotherapy
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Incyte Corporation
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
* Male or female subjects, age 18 years or older * Subjects with histologically or cytologically confirmed NSCLC, MEL (including I/O relapsed MEL or I/O refractory MEL), CRC, SCCHN, ovarian cancer, recurrent B cell NHL or HL, or glioblastoma * Presence of measurable disease by RECIST v1.1 for solid tumors or Cheson criteria for B cell NHL (including DLBCL) or HL. For subjects with glioblastoma, presence of measurable disease is not required. * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 * Fresh baseline tumor biopsies (defined as a biopsy specimen taken since completion of the most recent prior chemotherapy regimen) are required for all cohorts except glioblastoma
Exclusion criteria
* Laboratory and medical history parameters not within Protocol-defined range * Currently pregnant or breastfeeding * Subjects who have received prior immune checkpoint inhibitors or an IDO inhibitor (except select Phase 2 cohorts evaluating I/O relapsed or I/O refractory MEL). Subjects who have received experimental vaccines or other immune therapies should be discussed with the medical monitor to confirm eligibility * Untreated central nervous system (CNS) metastases or CNS metastases that have progressed * Subjects with any active or inactive autoimmune process * Evidence of interstitial lung disease or active, noninfectious pneumonitis * Subjects with any active or inactive autoimmune process * Ocular MEL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1, Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | Day 42 | A DLT was defined as occurrence of any treatment-emergent adverse event (TEAE) in Phase 1 Parts 1 and 2. DLT included all TEAE of specified grades such as 1) Hematologic toxicities - any Grade 4 thrombocytopenia or neutropenia, anemia, febrile neutropenia, ≥ Grade 3 hemolysis, thrombocytopenia and 2) Nonhematologic toxicities - Grade 4 AE, nausea, vomiting, or diarrhea, electrolyte abnormality, ≥ Grade 3 aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin elevation, Grade 2 AST/ALT with symptomatic liver inflammation, AST or ALT \> 3 × upper limit of normal (ULN) and concurrent total bilirubin \> 2 × ULN without initial findings of cholestasis, and any other ≥ Grade 3 toxicity. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug. |
| Phase 1, Part 2: Number of Participants With Dose Limiting Toxicities (DLTs) | Day 42 | A DLT was defined as occurrence of any treatment-emergent adverse event (TEAE) in Phase 1 Parts 1 and 2. DLT included all TEAE of specified grades such as 1) Hematologic toxicities - any Grade 4 thrombocytopenia or neutropenia, anemia, febrile neutropenia, ≥ Grade 3 hemolysis, thrombocytopenia and 2) Nonhematologic toxicities - Grade 4 AE, nausea, vomiting, or diarrhea, electrolyte abnormality, ≥ Grade 3 aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin elevation, Grade 2 AST/ALT with symptomatic liver inflammation, AST or ALT \> 3 × upper limit of normal (ULN) and concurrent total bilirubin \> 2 × ULN without initial findings of cholestasis, and any other ≥ Grade 3 toxicity. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug. |
| Phase 1, Parts 1 and 2: Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE) | up to approximately 39 months | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug. |
| Phase 2: Objective Response Rate (ORR) in Participants With Select Solid Tumors Per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 for Participants With Solid Tumors and Per Cheson Criteria for Participants With DLBCL | From first dose up end of the study (up to approximately 6 years) | ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per RECIST v1.1. CR per RECIST v 1.1 was defined as disappearance of all target lesions. PR per RECIST v 1.1 was defined as At least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters. Data is reported as per dose received by the participants with a particular cancer type. CR per Cheson criteria was defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR per Cheson criteria was defined as at least a 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses. |
| Phase 2: Progression Free Survival (PFS) | From first dose up end of the study (up to approximately 6 years) | PFS is defined as the time from randomization to the first documented progressive disease per RECIST v1.1 or death due to any cause, whichever occurs first. |
| Phase 2: Overall Survival (OS) Rate of Proportion With Glioblastoma | Month 9 | OS rate is defined as the proportion of participants alive 9 months after the start of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1, Part 2: ORR Per RECIST v1.1 and for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC | From first dose up end of the study (up to approximately 6 years) | ORR was defined as percentage of participants having CR or PR as determined by investigator assessment of radiographic disease per RECIST v1.1. CR per RECIST v 1.1 was defined as disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters. |
| Phase 2: Safety and Tolerability Measured by the Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Fatal Treatment Emergent AEs | up to approximately 35 months | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug. Adverse events of grade 5 which result in death are called as fatal AEs. |
| Phase 1, Part 1: ORR Per RECIST v1.1 for Participants With Solid Tumors; Per Cheson Criteria for Participants With B-cell NHL; and Per RANO and mRANO Criteria for Participants With GBM | From first dose up end of the study (up to approximately 6 years) | ORR was defined as percentage of participants having CR or PR as determined by investigator assessment of radiographic disease per RECIST v1.1. CR per RECIST v 1.1 was defined as disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters. Per Cheson criteria, CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR: at least a 50% decrease in SPD of up to 6 of the largest dominant nodes or nodal masses. Per RANO criteria, CR: Complete disappearance of all enhancing measurable and non-measurable disease sustained. PR: at least ≥50% decrease compared with baseline in the SOD of all measurable enhancing lesions sustained. |
| Phase 1, Part 2: Duration of Response (DOR) for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC | From first dose up end of the study (up to approximately 6 years) | DOR is defined as the time from the first overall response contributing to an objective response (CR or PR) to the earlier of the participant's death and first overall response of PD. CR was defined as disappearance of all target lesions. PR was defined as At least a 30% decrease in the SOD of target lesions, taking as reference the Baseline sum diameters. PD was defined as at least a 20% increase in the SOD of target lesions. |
| Phase 1, Part 2: PFS for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC | From first dose up end of the study (up to approximately 6 years) | PFS is defined as the time from randomization to the first documented progressive disease or death due to any cause, whichever occurs first. |
| Phase 2: Duration of Response | From first dose up end of the study (up to approximately 6 years) | DOR is defined as the time from the first overall response contributing to an objective response (CR or PR) to the earlier of the participant's death and first overall response of PD. CR was defined as disappearance of all target lesions. PR was defined as At least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters. PD was defined as at least a 20% increase in the SOD of target lesions. |
| Phase 2: Duration of Disease Control, Defined as CR, PR, and Stable Disease (SD) | From first dose up end of the study (up to approximately 6 years) | Duration of disease control is the time from the first dose to the first objective response of PD, or death, whichever occurs first, for participants who reported a best overall response of SD or better. PD was defined as at least a 20% increase in the SOD of target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the Baseline sum diameters. |
Countries
United Kingdom, United States
Participant flow
Recruitment details
Participants took part in 22 study sites in the United States and 2 study sites in the United Kingdom from 26 November 2014 to 16 June 2020.
Pre-assignment details
A total of 307 participants were enrolled in this study, 48 participants were enrolled in Phase 1 and 259 participants were enrolled in Phase 2. Participants in Phase 1 Part 2 and Phase 2 received dose per select solid tumor types (Colorectal, Melanoma I/O Naïve, Melanoma I/O relapsed, Melanoma I/O refractory, Non-small cell lung cancer (NSCLC), Ovarian, Squamous cell carcinoma of the head and neck (SCCHN), Diffuse large B-cell lymphoma (DLBCL) and Glioblastoma).
Participants by arm
| Arm | Count |
|---|---|
| Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg Participants received epacadostat 25 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, on Days 1, 15, 29, and 43 of each 8-week cycle. | 3 |
| Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg Participants received epacadostat 50 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle. | 6 |
| Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg Participants received epacadostat 100 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle. | 14 |
| Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg Participants received epacadostat 300 mg, orally, BID in combination of nivolumab 3 mg/kg, IV, Q3W, on Days 1, 15, 29, and 43 of each 8-week cycle. | 13 |
| Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with 5-FU/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated. | 6 |
| Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Pemetrexed /Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated. | 3 |
| Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 360 mg, IV, Q2W, on Day 1 of each 21-day cycle along with Paclitaxel/Platinum chemotherapy regimen IV. Participants were de-escalated to epacadostat 50 mg BID if 100 mg was not tolerated. | 3 |
| Phase 2: Epacadostat 100 mg + Nivolumab 240/480 mg Participants with select solid tumor types received epacadostat 100 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 and participants with melanoma I/O-relapsed and melanoma I/O-refractory enrolled in this arm received epacadostat 100 mg BID in combination with nivolumab 480 mg IV infusion Q4W on Days 1 and Day 29 of each 8-week cycle. | 83 |
| Phase 2: Epacadostat 300 mg + Nivolumab 240 mg Participants with select solid tumor types received epacadostat 300 mg BID in combination with nivolumab 240 mg IV infusion Q2W on Days 1, 15, 29, and 43 of each 8-week cycle. | 176 |
| Total | 307 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Completed 100 Day Safety Follow-up Period | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 3 | 11 |
| Overall Study | Death | 2 | 4 | 10 | 6 | 4 | 3 | 2 | 51 | 97 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 2 | 5 |
| Overall Study | Participants Decision: Consent Withdrawal from Study and Follow-up | 0 | 1 | 2 | 1 | 1 | 0 | 0 | 11 | 25 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Reason not Specified | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 12 |
| Overall Study | Site Terminated by Sponsor | 1 | 0 | 1 | 4 | 0 | 0 | 0 | 11 | 25 |
Baseline characteristics
| Characteristic | Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg | Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg | Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg | Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg | Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum | Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum | Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum | Phase 2: Epacadostat 100 mg + Nivolumab 240/480 mg | Phase 2: Epacadostat 300 mg + Nivolumab 240 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 50.0 years STANDARD_DEVIATION 26 | 62.5 years STANDARD_DEVIATION 12.41 | 57.5 years STANDARD_DEVIATION 13.27 | 61.6 years STANDARD_DEVIATION 10.67 | 64.3 years STANDARD_DEVIATION 6.38 | 67.7 years STANDARD_DEVIATION 6.43 | 70.3 years STANDARD_DEVIATION 11.37 | 56.7 years STANDARD_DEVIATION 13.82 | 62.6 years STANDARD_DEVIATION 12.12 | 60.7 years STANDARD_DEVIATION 12.33 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants | 11 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 5 Participants | 14 Participants | 13 Participants | 6 Participants | 3 Participants | 3 Participants | 77 Participants | 159 Participants | 283 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 6 Participants | 7 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 |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 4 Participants | 7 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 |
| 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 8 Participants | 14 Participants |
| Race (NIH/OMB) White | 3 Participants | 6 Participants | 13 Participants | 13 Participants | 5 Participants | 3 Participants | 3 Participants | 76 Participants | 160 Participants | 282 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 11 Participants | 5 Participants | 1 Participants | 1 Participants | 1 Participants | 46 Participants | 77 Participants | 145 Participants |
| Sex: Female, Male Male | 1 Participants | 5 Participants | 3 Participants | 8 Participants | 5 Participants | 2 Participants | 2 Participants | 37 Participants | 99 Participants | 162 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 |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 4 / 6 | 11 / 14 | 7 / 13 | 4 / 6 | 3 / 3 | 2 / 3 | 52 / 83 | 97 / 176 | 182 / 307 |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 14 / 14 | 13 / 13 | 6 / 6 | 3 / 3 | 3 / 3 | 81 / 83 | 173 / 176 | 302 / 307 |
| serious Total, serious adverse events | 0 / 3 | 3 / 6 | 4 / 14 | 4 / 13 | 4 / 6 | 2 / 3 | 2 / 3 | 40 / 83 | 89 / 176 | 148 / 307 |
Outcome results
Primary
Phase 1, Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
A DLT was defined as occurrence of any treatment-emergent adverse event (TEAE) in Phase 1 Parts 1 and 2. DLT included all TEAE of specified grades such as 1) Hematologic toxicities - any Grade 4 thrombocytopenia or neutropenia, anemia, febrile neutropenia, ≥ Grade 3 hemolysis, thrombocytopenia and 2) Nonhematologic toxicities - Grade 4 AE, nausea, vomiting, or diarrhea, electrolyte abnormality, ≥ Grade 3 aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin elevation, Grade 2 AST/ALT with symptomatic liver inflammation, AST or ALT \> 3 × upper limit of normal (ULN) and concurrent total bilirubin \> 2 × ULN without initial findings of cholestasis, and any other ≥ Grade 3 toxicity. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug.
Time frame: Day 42
Population: The Phase 1, Part 1 Safety Population includes all participants enrolled in the study who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg | Phase 1, Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg | Phase 1, Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg | Phase 1, Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg | Phase 1, Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
Primary
Phase 1, Part 2: Number of Participants With Dose Limiting Toxicities (DLTs)
A DLT was defined as occurrence of any treatment-emergent adverse event (TEAE) in Phase 1 Parts 1 and 2. DLT included all TEAE of specified grades such as 1) Hematologic toxicities - any Grade 4 thrombocytopenia or neutropenia, anemia, febrile neutropenia, ≥ Grade 3 hemolysis, thrombocytopenia and 2) Nonhematologic toxicities - Grade 4 AE, nausea, vomiting, or diarrhea, electrolyte abnormality, ≥ Grade 3 aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin elevation, Grade 2 AST/ALT with symptomatic liver inflammation, AST or ALT \> 3 × upper limit of normal (ULN) and concurrent total bilirubin \> 2 × ULN without initial findings of cholestasis, and any other ≥ Grade 3 toxicity. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug.
Time frame: Day 42
Population: The Phase 1, Part 2 Safety Population includes all participants enrolled in the study who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg | Phase 1, Part 2: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg | Phase 1, Part 2: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg | Phase 1, Part 2: Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
Primary
Phase 1, Parts 1 and 2: Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug.
Time frame: up to approximately 39 months
Population: The Phase 1, Parts 1 and 2 Safety Population includes all participants enrolled in the study who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg | Phase 1, Parts 1 and 2: Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE) | 3 Participants |
| Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg | Phase 1, Parts 1 and 2: Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE) | 6 Participants |
| Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg | Phase 1, Parts 1 and 2: Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE) | 14 Participants |
| Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg | Phase 1, Parts 1 and 2: Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE) | 13 Participants |
| Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum | Phase 1, Parts 1 and 2: Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE) | 6 Participants |
| Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum | Phase 1, Parts 1 and 2: Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE) | 3 Participants |
| Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum | Phase 1, Parts 1 and 2: Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE) | 3 Participants |
Primary
Phase 2: Objective Response Rate (ORR) in Participants With Select Solid Tumors Per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 for Participants With Solid Tumors and Per Cheson Criteria for Participants With DLBCL
ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per RECIST v1.1. CR per RECIST v 1.1 was defined as disappearance of all target lesions. PR per RECIST v 1.1 was defined as At least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters. Data is reported as per dose received by the participants with a particular cancer type. CR per Cheson criteria was defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR per Cheson criteria was defined as at least a 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses.
Time frame: From first dose up end of the study (up to approximately 6 years)
Population: The Phase 2 Full Analysis Population includes all participants enrolled in the study who received at least 1 dose of study drug. The data is reported per cancer type in this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg | Phase 2: Objective Response Rate (ORR) in Participants With Select Solid Tumors Per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 for Participants With Solid Tumors and Per Cheson Criteria for Participants With DLBCL | 3.8 percentage of participants |
| Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg | Phase 2: Objective Response Rate (ORR) in Participants With Select Solid Tumors Per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 for Participants With Solid Tumors and Per Cheson Criteria for Participants With DLBCL | 0.0 percentage of participants |
| Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg | Phase 2: Objective Response Rate (ORR) in Participants With Select Solid Tumors Per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 for Participants With Solid Tumors and Per Cheson Criteria for Participants With DLBCL | 62.0 percentage of participants |
| Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg | Phase 2: Objective Response Rate (ORR) in Participants With Select Solid Tumors Per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 for Participants With Solid Tumors and Per Cheson Criteria for Participants With DLBCL | 28.6 percentage of participants |
| Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum | Phase 2: Objective Response Rate (ORR) in Participants With Select Solid Tumors Per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 for Participants With Solid Tumors and Per Cheson Criteria for Participants With DLBCL | 28.6 percentage of participants |
| Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum | Phase 2: Objective Response Rate (ORR) in Participants With Select Solid Tumors Per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 for Participants With Solid Tumors and Per Cheson Criteria for Participants With DLBCL | 20.7 percentage of participants |
| Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum | Phase 2: Objective Response Rate (ORR) in Participants With Select Solid Tumors Per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 for Participants With Solid Tumors and Per Cheson Criteria for Participants With DLBCL | 13.8 percentage of participants |
| Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in SCCHN | Phase 2: Objective Response Rate (ORR) in Participants With Select Solid Tumors Per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 for Participants With Solid Tumors and Per Cheson Criteria for Participants With DLBCL | 25.8 percentage of participants |
| Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in Glioblastoma | Phase 2: Objective Response Rate (ORR) in Participants With Select Solid Tumors Per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 for Participants With Solid Tumors and Per Cheson Criteria for Participants With DLBCL | 0.0 percentage of participants |
Primary
Phase 2: Overall Survival (OS) Rate of Proportion With Glioblastoma
OS rate is defined as the proportion of participants alive 9 months after the start of treatment.
Time frame: Month 9
Population: The Phase 2 Full Analysis Population includes all participants enrolled in the study who take at least 1 dose of study drug. The data is reported for participants with Glioblastoma cancer type for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg | Phase 2: Overall Survival (OS) Rate of Proportion With Glioblastoma | 0.458 proportion of participants |
Primary
Phase 2: Progression Free Survival (PFS)
PFS is defined as the time from randomization to the first documented progressive disease per RECIST v1.1 or death due to any cause, whichever occurs first.
Time frame: From first dose up end of the study (up to approximately 6 years)
Population: The Phase 2 Full Analysis Population includes all participants enrolled in the study who take at least 1 dose of study drug. The data is reported per cancer type in this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg | Phase 2: Progression Free Survival (PFS) | 1.78 months |
| Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg | Phase 2: Progression Free Survival (PFS) | 1.64 months |
| Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg | Phase 2: Progression Free Survival (PFS) | NA months |
| Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg | Phase 2: Progression Free Survival (PFS) | 1.76 months |
| Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum | Phase 2: Progression Free Survival (PFS) | 2.55 months |
| Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum | Phase 2: Progression Free Survival (PFS) | 1.88 months |
| Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum | Phase 2: Progression Free Survival (PFS) | 1.88 months |
| Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in SCCHN | Phase 2: Progression Free Survival (PFS) | 3.62 months |
| Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in Glioblastoma | Phase 2: Progression Free Survival (PFS) | 1.84 months |
Secondary
Phase 1, Part 1: ORR Per RECIST v1.1 for Participants With Solid Tumors; Per Cheson Criteria for Participants With B-cell NHL; and Per RANO and mRANO Criteria for Participants With GBM
ORR was defined as percentage of participants having CR or PR as determined by investigator assessment of radiographic disease per RECIST v1.1. CR per RECIST v 1.1 was defined as disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters. Per Cheson criteria, CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms. PR: at least a 50% decrease in SPD of up to 6 of the largest dominant nodes or nodal masses. Per RANO criteria, CR: Complete disappearance of all enhancing measurable and non-measurable disease sustained. PR: at least ≥50% decrease compared with baseline in the SOD of all measurable enhancing lesions sustained.
Time frame: From first dose up end of the study (up to approximately 6 years)
Population: The Phase 1, Part 1 Full Analysis Population includes all participants enrolled in the study who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg | Phase 1, Part 1: ORR Per RECIST v1.1 for Participants With Solid Tumors; Per Cheson Criteria for Participants With B-cell NHL; and Per RANO and mRANO Criteria for Participants With GBM | 0.0 percentage of participants |
| Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg | Phase 1, Part 1: ORR Per RECIST v1.1 for Participants With Solid Tumors; Per Cheson Criteria for Participants With B-cell NHL; and Per RANO and mRANO Criteria for Participants With GBM | 0.0 percentage of participants |
| Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg | Phase 1, Part 1: ORR Per RECIST v1.1 for Participants With Solid Tumors; Per Cheson Criteria for Participants With B-cell NHL; and Per RANO and mRANO Criteria for Participants With GBM | 0.0 percentage of participants |
| Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg | Phase 1, Part 1: ORR Per RECIST v1.1 for Participants With Solid Tumors; Per Cheson Criteria for Participants With B-cell NHL; and Per RANO and mRANO Criteria for Participants With GBM | 23.1 percentage of participants |
Secondary
Phase 1, Part 2: Duration of Response (DOR) for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC
DOR is defined as the time from the first overall response contributing to an objective response (CR or PR) to the earlier of the participant's death and first overall response of PD. CR was defined as disappearance of all target lesions. PR was defined as At least a 30% decrease in the SOD of target lesions, taking as reference the Baseline sum diameters. PD was defined as at least a 20% increase in the SOD of target lesions.
Time frame: From first dose up end of the study (up to approximately 6 years)
Population: The Phase 1, Part 2 Full Analysis Population includes all participants enrolled in the study who received at least 1 dose of study drug. The data is reported only for responders for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg | Phase 1, Part 2: Duration of Response (DOR) for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC | 3.82 months |
| Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg | Phase 1, Part 2: Duration of Response (DOR) for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC | NA months |
| Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg | Phase 1, Part 2: Duration of Response (DOR) for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC | 3.93 months |
Secondary
Phase 1, Part 2: ORR Per RECIST v1.1 and for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC
ORR was defined as percentage of participants having CR or PR as determined by investigator assessment of radiographic disease per RECIST v1.1. CR per RECIST v 1.1 was defined as disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters.
Time frame: From first dose up end of the study (up to approximately 6 years)
Population: The Phase 1, Part 2 Full Analysis Population includes all participants enrolled in the study who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg | Phase 1, Part 2: ORR Per RECIST v1.1 and for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC | 50.0 percentage of participants |
| Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg | Phase 1, Part 2: ORR Per RECIST v1.1 and for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC | 33.3 percentage of participants |
| Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg | Phase 1, Part 2: ORR Per RECIST v1.1 and for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC | 100.0 percentage of participants |
Secondary
Phase 1, Part 2: PFS for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC
PFS is defined as the time from randomization to the first documented progressive disease or death due to any cause, whichever occurs first.
Time frame: From first dose up end of the study (up to approximately 6 years)
Population: The Phase 1, Part 2 Full Analysis Population includes all participants enrolled in the study who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg | Phase 1, Part 2: PFS for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC | 5.72 months |
| Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg | Phase 1, Part 2: PFS for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC | 2.83 months |
| Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg | Phase 1, Part 2: PFS for Participants With Advanced or Metastatic SCCHN and Advanced or Metastatic NSCLC | 6.10 months |
Secondary
Phase 2: Duration of Disease Control, Defined as CR, PR, and Stable Disease (SD)
Duration of disease control is the time from the first dose to the first objective response of PD, or death, whichever occurs first, for participants who reported a best overall response of SD or better. PD was defined as at least a 20% increase in the SOD of target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the Baseline sum diameters.
Time frame: From first dose up end of the study (up to approximately 6 years)
Population: The Phase 2 Full Analysis Population includes all participants enrolled in the study who received at least 1 dose of study drug. The data is reported per cancer type in this outcome measure. Overall number analyzed are the participants who had best overall response of stable disease or better.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg | Phase 2: Duration of Disease Control, Defined as CR, PR, and Stable Disease (SD) | 3.72 months |
| Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg | Phase 2: Duration of Disease Control, Defined as CR, PR, and Stable Disease (SD) | 4.57 months |
| Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg | Phase 2: Duration of Disease Control, Defined as CR, PR, and Stable Disease (SD) | NA months |
| Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg | Phase 2: Duration of Disease Control, Defined as CR, PR, and Stable Disease (SD) | NA months |
| Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum | Phase 2: Duration of Disease Control, Defined as CR, PR, and Stable Disease (SD) | NA months |
| Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum | Phase 2: Duration of Disease Control, Defined as CR, PR, and Stable Disease (SD) | NA months |
| Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum | Phase 2: Duration of Disease Control, Defined as CR, PR, and Stable Disease (SD) | 5.86 months |
| Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in SCCHN | Phase 2: Duration of Disease Control, Defined as CR, PR, and Stable Disease (SD) | 10.89 months |
| Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in Glioblastoma | Phase 2: Duration of Disease Control, Defined as CR, PR, and Stable Disease (SD) | 3.72 months |
Secondary
Phase 2: Duration of Response
DOR is defined as the time from the first overall response contributing to an objective response (CR or PR) to the earlier of the participant's death and first overall response of PD. CR was defined as disappearance of all target lesions. PR was defined as At least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the Baseline sum diameters. PD was defined as at least a 20% increase in the SOD of target lesions.
Time frame: From first dose up end of the study (up to approximately 6 years)
Population: The Phase 2 Full Analysis Population includes all participants enrolled in the study who received at least 1 dose of study drug. The data is reported only for responders and per cancer type for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg | Phase 2: Duration of Response | NA months |
| Phase 1, Part 1: Epacadostat 100 mg + Nivolumab 3 mg | Phase 2: Duration of Response | NA months |
| Phase 1, Part 1: Epacadostat 300 mg + Nivolumab 3 mg | Phase 2: Duration of Response | NA months |
| Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + 5-FU/Platinum | Phase 2: Duration of Response | NA months |
| Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Pemetrexed/ Platinum | Phase 2: Duration of Response | NA months |
| Phase 1, Part 2: Epacadostat 100 mg + Nivolumab 360 mg + Paclitaxel/ Platinum | Phase 2: Duration of Response | 3.93 months |
| Phase 2 Epacadostat 100/300 mg + Nivolumab 240 mg in SCCHN | Phase 2: Duration of Response | NA months |
Secondary
Phase 2: Safety and Tolerability Measured by the Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Fatal Treatment Emergent AEs
An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and up to 100 days after last dose of study drug. Adverse events of grade 5 which result in death are called as fatal AEs.
Time frame: up to approximately 35 months
Population: The Phase 2 Safety population includes all participants enrolled in the study who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg | Phase 2: Safety and Tolerability Measured by the Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Fatal Treatment Emergent AEs | Participants with Treatment Emergent Adverse Events | 82 Participants |
| Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg | Phase 2: Safety and Tolerability Measured by the Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Fatal Treatment Emergent AEs | Participants with Serious Treatment Emergent AEs | 40 Participants |
| Phase 1, Part 1: Epacadostat 25 mg + Nivolumab 3 mg | Phase 2: Safety and Tolerability Measured by the Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Fatal Treatment Emergent AEs | Participants with Fatal Treatment Emergent AEs | 4 Participants |
| Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg | Phase 2: Safety and Tolerability Measured by the Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Fatal Treatment Emergent AEs | Participants with Serious Treatment Emergent AEs | 89 Participants |
| Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg | Phase 2: Safety and Tolerability Measured by the Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Fatal Treatment Emergent AEs | Participants with Treatment Emergent Adverse Events | 176 Participants |
| Phase 1, Part 1: Epacadostat 50 mg + Nivolumab 3 mg | Phase 2: Safety and Tolerability Measured by the Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Fatal Treatment Emergent AEs | Participants with Fatal Treatment Emergent AEs | 5 Participants |