A Study of Epacadostat in Combination With Pembrolizumab and Chemotherapy in Participants With Advanced or Metastatic Solid Tumors (ECHO-207/KEYNOTE-723)
- Conditions
- Solid Tumor
- Interventions
- Registration Number
- NCT03085914
- Lead Sponsor
- Incyte Corporation
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 70
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment Group A Epacadostat Epacadostat + pembrolizumab + mFOLFOX6 (oxaliplatin, leucovorin, 5-fluorouracil) Treatment Group D Epacadostat Epacadostat + pembrolizumab + pemetrexed and investigators choice of platinum agent Treatment Group F Epacadostat Epacadostat + pembrolizumab + gemcitabine and investigators choice of platinum agent Treatment Group G Epacadostat Epacadostat + pembrolizumab + investigators choice of platinum agent and 5-fluorouracil Treatment Group B nab-Paclitaxel Epacadostat + pembrolizumab + gemcitabine and nab-paclitaxel Treatment Group D Investigator's choice of platinum agent Epacadostat + pembrolizumab + pemetrexed and investigators choice of platinum agent Treatment Group E Epacadostat Epacadostat + pembrolizumab + cyclophosphamide Treatment Group G Investigator's choice of platinum agent Epacadostat + pembrolizumab + investigators choice of platinum agent and 5-fluorouracil Treatment Group D Carboplatin Epacadostat + pembrolizumab + pemetrexed and investigators choice of platinum agent Treatment Group C Paclitaxel Epacadostat + pembrolizumab + carboplatin and paclitaxel Treatment Group A Pembrolizumab Epacadostat + pembrolizumab + mFOLFOX6 (oxaliplatin, leucovorin, 5-fluorouracil) Treatment Group A Oxaliplatin Epacadostat + pembrolizumab + mFOLFOX6 (oxaliplatin, leucovorin, 5-fluorouracil) Treatment Group A Leucovorin Epacadostat + pembrolizumab + mFOLFOX6 (oxaliplatin, leucovorin, 5-fluorouracil) Treatment Group A 5-Fluorouracil Epacadostat + pembrolizumab + mFOLFOX6 (oxaliplatin, leucovorin, 5-fluorouracil) Treatment Group B Epacadostat Epacadostat + pembrolizumab + gemcitabine and nab-paclitaxel Treatment Group B Pembrolizumab Epacadostat + pembrolizumab + gemcitabine and nab-paclitaxel Treatment Group B Gemcitabine Epacadostat + pembrolizumab + gemcitabine and nab-paclitaxel Treatment Group C Epacadostat Epacadostat + pembrolizumab + carboplatin and paclitaxel Treatment Group C Pembrolizumab Epacadostat + pembrolizumab + carboplatin and paclitaxel Treatment Group C Carboplatin Epacadostat + pembrolizumab + carboplatin and paclitaxel Treatment Group D Pemetrexed Epacadostat + pembrolizumab + pemetrexed and investigators choice of platinum agent Treatment Group D Pembrolizumab Epacadostat + pembrolizumab + pemetrexed and investigators choice of platinum agent Treatment Group D Cisplatin Epacadostat + pembrolizumab + pemetrexed and investigators choice of platinum agent Treatment Group E Pembrolizumab Epacadostat + pembrolizumab + cyclophosphamide Treatment Group E Cyclophosphamide Epacadostat + pembrolizumab + cyclophosphamide Treatment Group F Pembrolizumab Epacadostat + pembrolizumab + gemcitabine and investigators choice of platinum agent Treatment Group F Gemcitabine Epacadostat + pembrolizumab + gemcitabine and investigators choice of platinum agent Treatment Group G Pembrolizumab Epacadostat + pembrolizumab + investigators choice of platinum agent and 5-fluorouracil Treatment Group G Carboplatin Epacadostat + pembrolizumab + investigators choice of platinum agent and 5-fluorouracil Treatment Group G 5-Fluorouracil Epacadostat + pembrolizumab + investigators choice of platinum agent and 5-fluorouracil Treatment Group G Cisplatin Epacadostat + pembrolizumab + investigators choice of platinum agent and 5-fluorouracil
- Primary Outcome Measures
Name Time Method Phases 1 & 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs Up to 21 months A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of epacadostat, pembrolizumab, or chemotherapy. Serious adverse event is defined as an event that meets 1 of the following criteria: is fatal or life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability, incapacity, or a substantial disruption of a person's ability to conduct normal life functions, constitutes a congenital anomaly or birth defect,is a medically important event that may jeopardize the participant or may require medical or surgical intervention to prevent 1 of the outcomes listed above.
Phases 1 and 2: Number of Participants With Dose Limiting Toxicities (DLTs) 28 days A DLT was defined as the occurrence of any of the protocol-specified toxicities occurring up to and including Day 28 for the cohorts where mFOLFOX6 and nab-paclitaxel/gemcitabine are administered and Day 21 for all other chemotherapy regimens in Phase 1, except those with a clear alternative explanation (eg, disease progression) or transient (≤ 72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination.
Phases 1 and 2: Objective Response Rate (ORR) Up to Week 18 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 Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (15)
The Angeles Clinic and Research Institute
🇺🇸Los Angeles, California, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
Vanderbilt University; Henry Joyce Cancer Clinic
🇺🇸Nashville, Tennessee, United States
Huntsman Cancer Institute at University of Utah
🇺🇸Salt Lake City, Utah, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
University of California San Diego Medical Center, Moores Cancer Center
🇺🇸La Jolla, California, United States
University of Pennsylvania Health System
🇺🇸Philadelphia, Pennsylvania, United States
Tennessee Oncology - Nashville; The Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
University of Pittsburgh Cancer Institute
🇺🇸Pittsburgh, Pennsylvania, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Carolina Bio-Oncology Institute, PLLC
🇺🇸Huntersville, North Carolina, United States