A Study of Epacadostat in Combination With Pembrolizumab and Chemotherapy in Participants With Advanced or Metastatic Solid Tumors (ECHO-207/KEYNOTE-723)

Incyte

Status and phase: Completed; Phase 2; Phase 1

Conditions: Solid Tumor

Treatments: Drug: Carboplatin; Drug: Pemetrexed; Drug: Epacadostat; Drug: Paclitaxel; Drug: Pembrolizumab; Drug: nab-Paclitaxel; Drug: Gemcitabine; Drug: Investigator's choice of platinum agent; Drug: 5-Fluorouracil; Drug: Cyclophosphamide; Drug: Leucovorin; Drug: Oxaliplatin; Drug: Cisplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT03085914

INCB 24360-207 / ECHO-207

2016-004678-16 (EudraCT Number)

Details and patient eligibility

About

This was an open-label, nonrandomized, Phase 1/2 study designed to determine the safety, tolerability, and efficacy of epacadostat when given in combination with pembrolizumab and 7 different chemotherapy regimens described as Treatment Groups A through G below (see Study Drug and Background Therapies, Dose, and Mode of Administration). Phase 1 consisted of a 3 + 3 + 3 design intended to determine the MTD or PAD of epacadostat when given in combination with pembrolizumab and chemotherapy; efficacy was also explored.

Phase 2 was designed to enroll efficacy expansion cohorts to further evaluate the safety, tolerability, and efficacy of epacadostat at the MTD or PAD (as selected in Phase 1) when given in combination with pembrolizumab and chemotherapy. Each efficacy expansion cohort was to enroll participants with 1 specific type of advanced or metastatic solid tumor. Additional cohorts (ie, the mandatory biopsy cohorts) were designed to evaluate changes in the tumor microenvironment in participants with any advanced or metastatic solid tumor who had progressed on previous therapy with a PD-1 or a PD-L1 inhibitor.

No participants were enrolled in any Phase 2 efficacy expansion cohort, or in any Phase 2 mandatory biopsy cohort receiving Treatment A, B, F, or G. Phase 2 mandatory biopsy cohort participants received Treatments C, D, or E (ie, were included in Treatment Groups C, D, or E). Participants were assigned to a treatment group based on the chemotherapy regimen most appropriate for their tumor type.

Enrollment: 70 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically confirmed diagnosis of selected advanced or metastatic solid tumors.
• Presence of measurable disease per RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion criteria

• Laboratory and medical history parameters not within the Protocol-defined range.
• Receipt of anticancer medications or investigational drugs within the Protocol-defined intervals before the first administration of study drug.
• Previous radiotherapy within 2 weeks of starting study therapy.
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has not recovered to ≤ Grade 1 from toxic effects of previous therapy and/or complications from previous surgical intervention before starting study therapy.
• Receipt of a live vaccine within 30 days of planned start of study therapy.
• Active infection requiring systemic therapy.
• Subjects who have any active or inactive autoimmune disease or syndrome.
• Women who are pregnant or breastfeeding.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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70 participants in 7 patient groups

Treatment Group A

Experimental group

Description:

Epacadostat + pembrolizumab + mFOLFOX6 (oxaliplatin, leucovorin, 5-fluorouracil)

Treatment:

Drug: 5-Fluorouracil

Drug: Oxaliplatin

Drug: Pembrolizumab

Drug: 5-Fluorouracil

Drug: Epacadostat

Drug: Leucovorin

Treatment Group B

Experimental group

Description:

Epacadostat + pembrolizumab + gemcitabine and nab-paclitaxel

Treatment:

Drug: nab-Paclitaxel

Drug: Gemcitabine

Drug: Pembrolizumab

Drug: Epacadostat

Treatment Group C

Experimental group

Description:

Epacadostat + pembrolizumab + carboplatin and paclitaxel

Treatment:

Drug: Carboplatin

Drug: Paclitaxel

Drug: Pembrolizumab

Drug: Carboplatin

Drug: Epacadostat

Treatment Group D

Experimental group

Description:

Epacadostat + pembrolizumab + pemetrexed and investigators choice of platinum agent

Treatment:

Drug: Cisplatin

Drug: Carboplatin

Drug: Investigator's choice of platinum agent

Drug: Pembrolizumab

Drug: Carboplatin

Drug: Pemetrexed

Drug: Epacadostat

Treatment Group E

Experimental group

Description:

Epacadostat + pembrolizumab + cyclophosphamide

Treatment:

Drug: Cyclophosphamide

Drug: Pembrolizumab

Drug: Epacadostat

Treatment Group F

Experimental group

Description:

Epacadostat + pembrolizumab + gemcitabine and investigators choice of platinum agent

Treatment:

Drug: Gemcitabine

Drug: Pembrolizumab

Drug: Epacadostat

Treatment Group G

Experimental group

Description:

Epacadostat + pembrolizumab + investigators choice of platinum agent and 5-fluorouracil

Treatment:

Drug: Cisplatin

Drug: Carboplatin

Drug: 5-Fluorouracil

Drug: Investigator's choice of platinum agent

Drug: Pembrolizumab

Drug: 5-Fluorouracil

Drug: Carboplatin

Drug: Epacadostat