Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT02862457 | Study of Epacadostat (INCB024360) Alone and In Combination With Pembrolizumab (MK-3475) With Chemotherapy and Pembrolizumab Without Chemotherapy in Participants With Advanced Solid Tumors (MK-3475-434) | PHASE1 | COMPLETED | 34 | — | — | Aug 23, 2016 | Nov 20, 2020 | Aug 19, 2022 | - | — |
A DLT was defined as the occurrence of any treatment-emergent adverse event occurring up to and including Study Day 7 for Part A Cohort 1 or Day 21 for Part A Cohort 2 and Part B. The following criteria defined DLTs: Grade (G) 4 thrombocytopenia; G4 neutropenia (despite optimal supportive care in Part B) lasting \>1 week; febrile neutropenia (only if considered clinically significant in Part B); G4 toxicity; G3 laboratory abnormality lasting \>1 week: G3 toxicity excluding nausea or vomiting controlled within 72 hours, rash in the absence of desquamation, no mucosal involvement, does not require systemic steroids, and resolves to G1 by the next scheduled dose of pembrolizumab or 14 days; G2 or higher episcleritis, uveitis, or iritis; unable to receive 75% of epacadostat or 1 dose of pembrolizumab during the DLT observation period because of toxicity, even if the toxicity does not meet DLT criteria; or \>2 week delay in initiating Cycle 2 due to toxicity.
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The number of participants who experienced an AE was reported for each arm.
An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The number of participants who discontinued due to an AE was reported for each arm.
| Arm | Type | Description |
|---|---|---|
| Part A Cohort 1: epacadostat 25 mg | EXPERIMENTAL | Participants received 25 mg of epacadostat orally twice daily (BID) alone on Days 1-5 of Cycle 1 (28-day cycle) with a washout on Days 6 and 7. On Day 8 participants received a one-time intravenous (IV) infusion of 200 mg pembrolizumab while continuing to receive 25 mg of epacadostat BID on Days 8-28. For each 21-day cycle thereafter, participants received a one-time IV infusion of 200 mg pembrolizumab on Day 1 and received 25 mg of epacadostat BID on Days 1-21 for up to 35 cycles (approximately 2 years). |
| Part A Cohort 1: epacadostat 100 mg | EXPERIMENTAL | Participants received 100 mg of epacadostat orally BID alone on Days 1-5 of Cycle 1 (28-day cycle) with a washout on Days 6 and 7. On Day 8 participants received a one-time IV infusion of 200 mg pembrolizumab while continuing to receive 100 mg of epacadostat BID on Days 8-28. For each 21-day cycle thereafter, participants received a one-time IV infusion of 200 mg pembrolizumab on Day 1 and received 100 mg of epacadostat BID on Days 1-21 for up to 35 cycles (approximately 2 years). |
| Part A Cohort 2: epacadostat 25 mg+pembrolizumab | EXPERIMENTAL | For each 21-day cycle, participants received a one-time IV infusion of 200 mg pembrolizumab on Day 1 and received 25 mg of epacadostat orally BID on Days 1-21 for up to 35 cycles (approximately 2 years). |
| Part A Cohort 2: epacadostat 100 mg+pembrolizumab | EXPERIMENTAL | For each 21-day cycle, participants received a one-time IV infusion of 200 mg pembrolizumab on Day 1 and received 100 mg of epacadostat orally BID on Days 1-21 for up to 35 cycles (approximately 2 years). |
| Part B Cohort 1: pembrolizumab+cisplatin+pemetrexed | EXPERIMENTAL | For each 21-day cycle, participants received a one-time IV infusion of 200 mg pembrolizumab on Day 1 and 100 mg of epacadostat orally BID on Days 1-21 for up to 35 cycles (approximately 2 years). For the first 4 cycles, participants also received a one-time IV infusion of 75 mg/m\^2 cisplatin and 500 mg/m\^2 pemetrexed on Day 1. Treatment with epacadostat was stopped with protocol amendment 02. |
| Part B Cohort 2: pembrolizumab+carboplatin+pemetrexed | EXPERIMENTAL | For each 21-day cycle, participants received a one-time IV infusion of 200 mg pembrolizumab on Day 1 and 100 mg of epacadostat orally BID on Days 1-21 for up to 35 cycles (approximately 2 years). For the first 4 cycles, participants also received a one-time IV infusion of Area Under the Curve (AUC) 5 carboplatin and 500 mg/m\^2 pemetrexed on Day 1. Treatment with epacadostat was stopped with protocol amendment 02. |
| Part B Cohort 3: pembrolizumab+carboplatin+paclitaxel | EXPERIMENTAL | For each 21-day cycle, participants received a one-time IV infusion of 200 mg pembrolizumab on Day 1 and 100 mg of epacadostat orally BID on Days 1-21 for up to 35 cycles (approximately 2 years). For the first 4 cycles, participants also received a one-time IV infusion of AUC 6 carboplatin and 200 mg/m\^2 paclitaxel on Day 1. Treatment with epacadostat was stopped with protocol amendment 02. |
| Name | Type | Description |
|---|---|---|
| Epacadostat 25 mg | DRUG | Oral administration |
| Epacadostat 100 mg | DRUG | Oral administration |
| pembrolizumab 200 mg | BIOLOGICAL | Intravenous (IV) infusion |
| Cisplatin 75 mg/m^2 | DRUG | IV infusion |
| Carboplatin Area Under the Curve (AUC) 5 | DRUG | IV infusion |
| Pemetrexed 500 mg/m^2 | DRUG | IV infusion |
| Paclitaxel 200 mg/m^2 | DRUG | IV infusion |
| Carboplatin AUC 6 | DRUG | IV infusion |
Inclusion Criteria: * For Part A: Has a histologically-confirmed metastatic or locally advanced solid tumor that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist. * For Part B: Has a histologically-confirmed or cytologicall...