Epacadostat and Pembrolizumab in Treating Patients With Metastatic or Unresectable Gastroesophageal Junction or Gastric Cancer

Phase 2

Completed

• Conditions: Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Recurrent Esophageal Carcinoma; Recurrent Gastric Carcinoma; Stage IV Esophageal Cancer AJCC v7; Stage IV Gastric Cancer AJCC v7; Unresectable Esophageal Carcinoma
• Interventions: Drug: Epacadostat; Drug: Pembrolizumab

• Registration Number: NCT03196232
• Lead Sponsor: George Albert Fisher

Brief Summary

This phase 2 trial evaluates the benefit of epacadostat plus pembrolizumab in combination to treat patients with gastroesophageal junction or gastric cancer that has spread to other parts of the body and cannot be removed by surgery. Epacadostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells. Giving epacadostat and pembrolizumab may work better in treating patients with gastroesophageal junction or gastric cancer.

Detailed Description

Patients receive epacadostat orally (PO) twice daily (BID) on Days 1 to 21 and pembrolizumab intravenously (IV) over 30 minutes on Day 1. Courses repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 9 weeks for 18 months, and then every 12 weeks thereafter.

PRIMARY OBJECTIVES:

Assess 6-month progression free survival (PFS).

SECONDARY OBJECTIVES:

* To evaluate objective response rate (RR) by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 and immune-related response criteria (irRC).

* Evaluate overall survival (OS).

* Assess the safety and tolerability of epacadostat in combination with pembrolizumab by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03.

TERTIARY OBJECTIVES:

* Determine the responder rate defined as the proportion of subjects with an increased ratio of CD8+ to Treg cells in on-treatment compared with pre-treatment biopsies.

* Identify putative immunologic biomarkers of tumor response.

Study Timeline

• Study First Submitted: 2017-06-20
• Study First Submitted QC: 2017-06-20
• Study First Posted: 2017-06-22
• Study Start: 2017-09-13
• Primary Completion: 2018-05-29
• Study Completion: 2018-05-29
• Results First Submitted: 2020-03-06
• Results First Submitted QC: 2020-06-05
• Results First Posted: 2020-06-22
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-04
• Last Update Posted: 2024-01-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (epacadostat, pembrolizumab)	Epacadostat	Participants receive oral epacadostat BID on Days 1 to 21 and pembrolizumab IV over 30 minutes on Day 1, with cycles repeating every 21 days for up to 24 months, in the absence of disease progression or unacceptable toxicity.
Treatment (epacadostat, pembrolizumab)	Pembrolizumab	Participants receive oral epacadostat BID on Days 1 to 21 and pembrolizumab IV over 30 minutes on Day 1, with cycles repeating every 21 days for up to 24 months, in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	6 months	Progression-free survival (PFS) was assessed as the number of participants remaining alive without progression 6 months after beginning treatment. The outcome is reported as a number without dispersion.

Secondary Outcome Measures

Name	Time	Method
Response Rate	Up to 6 months	Therapeutic response was assessed per the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Criteria are: * Complete Response (CR) = Disappearance of all target lesions; * Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions; * Overall Response (OR) = CR + PR; * Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions; * Stable disease (SD) = Small changes that do not meet any of the above criteria; The outcome is reported as the number of participants with a documented clinical response (ie, either PR or CR) at 6 months after initiation of treatment.
Overall Survival	6 months	Overall survival (OS) was assessed as the number of participants remaining alive 6 months after beginning treatment. The outcome is reported as a number without dispersion.
Number of Adverse Events	Up to 6 months	Participants were monitored for adverse events. The outcome is reported as the overall number of adverse events of any grade, a number without dispersion.
Number of Adverse Events ≥ Grade 3	Up to 6 months	Adverse events were assessed per the Common Terminology Criteria for Adverse Events v4.03. The outcome is reported as the number of adverse events ≥ Grade 3, a number without dispersion.
Treatment Delay or Reduction	Up to 6 months	The assessment for clinical value of the treatment combination included treatment delays or reductions, a measure of how well the combination treatment was tolerated. The outcome is reported as the number of participants that experienced a treatment delay, or reduction in treatment dose level, a number without dispersion.

Trial Locations

Locations (1)

Stanford University, School of Medicine; 🇺🇸 Palo Alto, California, United States