Advanced Malignancies, Metastatic Cancer
Conditions
Keywords
cervical cancer, endometrial cancer, gastric cancer (including stomach and gastroesophageal junction (GEJ)), esophageal cancer, hepatocellular carcinoma (HCC), melanoma (mucosal or cutaneous), Merkel cell carcinoma, mesothelioma, microsatellite instability-high (MSI-H), solid tumors, 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)
Brief summary
The purpose of this study is to determine the safety, tolerability, and efficacy of INCAGN01876 when given in combination with immune therapies.
Interventions
DRUGINCAGN01876
In Phase 1 subjects will receive INCAGN01876 administered intravenously (IV) at the protocol-defined dose and schedule according to cohort and treatment group enrollment. In Phase 2, subjects will be administered IV study drug at the recommended dose from Phase 1.
DRUGEpacadostat
Epacadostat will be self-administered orally at the protocol-defined dose.
DRUGPembrolizumab
Pembrolizumab will be administered IV at the protocol-defined dose.
Sponsors
Incyte Biosciences International Sàrl
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
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 melanoma, RCC, and urothelial carcinoma. * Presence of measurable disease based on RECIST v1.1. * Eastern Cooperative Oncology Group performance status of 0 or 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 and Phase 2: Participants With Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability] | Screening through 60 days after end of treatment, up to approximately 18 months | A TEAE is any adverse event (AE) either reported for the first time or worsening of a pre-existing event after the first dose of study treatment. |
| Phase 1 and Phase 2 : ORR Based on RECIST v1.1 and mRECIST | Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months | Defined as the percentage of participants having a CR or PR based on investigator assessment per RECIST v1.1. |
| Phase 2: Complete Response Rate (CRR) Based on RECIST v1.1 | Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months | Defined as the percentage of checkpoint inhibitor-naive melanoma participants who have a CR based on investigator assessment per RECIST v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 & Phase 2: Progression-free Survival Based on RECIST v1.1 and mRECIST | Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months | Defined as the time from the start of combination therapy until the earliest date of disease progression or death due to any cause. |
| Phase 1 & Phase 2: Disease Control Rate Based on RECIST v1.1 and mRECIST | Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months. | Defined as the percentage of participants having CR, PR, or stable disease (SD) based on investigator assessment per RECIST v1.1. |
| Phase 1 & Phase 2: Overall Survival | At 1 year and 2 years. | Defined as the time from the start of combination therapy until death due to any cause. |
| Phase 1 & Phase 2: Duration of Response Based on RECIST v1.1 and mRECIST | Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months | Defined as the time from the earliest date of disease response (CR or PR) until earliest date of disease progression or death due to any cause. |
| Phase 1 & Phase 2: Duration of Disease Control Based on RECIST v1.1 and mRECIST | Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months | Defined as time from first report of SD or better until disease progression or death from any cause. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 2 different sites in USA. A total of 10 participants were enrolled in the study.
Pre-assignment details
A total of 10 participants were screened and enrolled in the study.
Participants by arm
| Arm | Count |
|---|---|
| INCAGN01876 + Pembrolizumab + Epacadostat INCAGN01876 in combination with pembrolizumab and epacadostat | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 4 |
| Overall Study | Study Terminated By Sponsor | 2 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | INCAGN01876 + Pembrolizumab + Epacadostat |
|---|---|
| Age, Continuous | 64.2 years STANDARD_DEVIATION 13.73 |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 9 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White/Caucasian | 8 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 10 | 4 / 10 |
| other Total, other adverse events | 10 / 10 | 10 / 10 |
| serious Total, serious adverse events | 3 / 10 | 3 / 10 |
Outcome results
Primary
Phase 1 and Phase 2 : ORR Based on RECIST v1.1 and mRECIST
Defined as the percentage of participants having a CR or PR based on investigator assessment per RECIST v1.1.
Time frame: Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months
Population: The FAS includes all participants enrolled in the study who received at least 1 dose of INCAGN01876, pembrolizumab, or epacadostat.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| INCAGN01876 + Pembrolizumab + Epacadostat | Phase 1 and Phase 2 : ORR Based on RECIST v1.1 and mRECIST | 3 Participants |
Primary
Phase 1 and Phase 2: Participants With Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability]
A TEAE is any adverse event (AE) either reported for the first time or worsening of a pre-existing event after the first dose of study treatment.
Time frame: Screening through 60 days after end of treatment, up to approximately 18 months
Population: The FAS includes all participants enrolled in the study who received at least 1 dose of INCAGN01876, pembrolizumab, or epacadostat.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| INCAGN01876 + Pembrolizumab + Epacadostat | Phase 1 and Phase 2: Participants With Treatment-Emergent Adverse Events (TEAEs) [Safety and Tolerability] | 10 Participants |
Primary
Phase 2: Complete Response Rate (CRR) Based on RECIST v1.1
Defined as the percentage of checkpoint inhibitor-naive melanoma participants who have a CR based on investigator assessment per RECIST v1.1
Time frame: Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months
Population: The study was terminated early and no participants enrolled in Phase 2 of the study.
Secondary
Phase 1 & Phase 2: Disease Control Rate Based on RECIST v1.1 and mRECIST
Defined as the percentage of participants having CR, PR, or stable disease (SD) based on investigator assessment per RECIST v1.1.
Time frame: Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months.
Population: The FAS includes all participants enrolled in the study who received at least 1 dose of INCAGN01876, pembrolizumab, or epacadostat.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| INCAGN01876 + Pembrolizumab + Epacadostat | Phase 1 & Phase 2: Disease Control Rate Based on RECIST v1.1 and mRECIST | 7 Participants |
Secondary
Phase 1 & Phase 2: Duration of Disease Control Based on RECIST v1.1 and mRECIST
Defined as time from first report of SD or better until disease progression or death from any cause.
Time frame: Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months
Population: The FAS includes all participants enrolled in the study who received at least 1 dose of INCAGN01876, pembrolizumab, or epacadostat.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| INCAGN01876 + Pembrolizumab + Epacadostat | Phase 1 & Phase 2: Duration of Disease Control Based on RECIST v1.1 and mRECIST | mRECIST | NA days |
| INCAGN01876 + Pembrolizumab + Epacadostat | Phase 1 & Phase 2: Duration of Disease Control Based on RECIST v1.1 and mRECIST | RECIST | 525 days |
Secondary
Phase 1 & Phase 2: Duration of Response Based on RECIST v1.1 and mRECIST
Defined as the time from the earliest date of disease response (CR or PR) until earliest date of disease progression or death due to any cause.
Time frame: Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months
Population: The FAS includes all participants enrolled in the study who received at least 1 dose of INCAGN01876, pembrolizumab, or epacadostat.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| INCAGN01876 + Pembrolizumab + Epacadostat | Phase 1 & Phase 2: Duration of Response Based on RECIST v1.1 and mRECIST | NA days |
Secondary
Phase 1 & Phase 2: Overall Survival
Defined as the time from the start of combination therapy until death due to any cause.
Time frame: At 1 year and 2 years.
Population: The FAS includes all participants enrolled in the study who received at least 1 dose of INCAGN01876, pembrolizumab, or epacadostat.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| INCAGN01876 + Pembrolizumab + Epacadostat | Phase 1 & Phase 2: Overall Survival | 25.59 months |
Secondary
Phase 1 & Phase 2: Progression-free Survival Based on RECIST v1.1 and mRECIST
Defined as the time from the start of combination therapy until the earliest date of disease progression or death due to any cause.
Time frame: Assessed every 9 weeks for 12 months, then every 12 weeks, up to 18 months
Population: The FAS includes all participants enrolled in the study who received at least 1 dose of INCAGN01876, pembrolizumab, or epacadostat.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| INCAGN01876 + Pembrolizumab + Epacadostat | Phase 1 & Phase 2: Progression-free Survival Based on RECIST v1.1 and mRECIST | mRECIST | 17.36 months |
| INCAGN01876 + Pembrolizumab + Epacadostat | Phase 1 & Phase 2: Progression-free Survival Based on RECIST v1.1 and mRECIST | RECIST | 4.20 months |