FLX475 Combined With Pembrolizumab in Patients With Advanced or Metastatic Gastric Cancer

A Phase 2 Study to Assess the Safety, Efficacy of FLX475 Combined With Pembrolizumab in Patients With Advanced or Metastatic Gastric Cancer

This clinical study is a Phase 2, open-label study to assess the efficacy, safety profile of FLX475 combined with pembrolizumab in patients with advanced or metastatic gastric cancer. This study is designed to assess the potential anti-tumor activity when administered at the 100mg QD of FLX475 with pembrolizumab and will be conducted (2) cohorts as detailed below.

• Cohort 1: EBV negative / CPI naïve gastric cancer subjects who have progressed on at least 2 prior systemic treatments for advanced or metastatic gastric cancer
• Cohort 2: EBV positive / CPI naïve gastric cancer subjects who had at least 1 prior systemic treatment for advanced or metastatic gastric cancer

Approximately 90 subjects may be enrolled across two cohorts to examine the safety and efficacy.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Drug: FLX475

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• South Korea
  • Seoul, South Korea
    • Asan Medical Center
  • Seoul, South Korea
    • Korea University Guro Hospital
  • Seoul, South Korea
    • Samsung Medical Center
  • Seoul, South Korea
    • Seoul National University Hospital
  • Seoul, South Korea
    • Gangnam Severance Hospital
  • Seoul, South Korea
    • Severance Hospital
  • Gyeonggi-do
    • Anyang-si, Gyeonggi-do, South Korea
      • Hanllym University Medical Center
    • Seongnam-si, Gyeonggi-do, South Korea
      • Seoul National University Bundang Hospital
    • Suwon, Gyeonggi-do, South Korea
      • The Catholic University of Korea St. Vincent Hospital
  • Jeollanam-do
    • Hwasun, Jeollanam-do, South Korea
      • Chonnam National University Hwasun Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• All patients must have histologically or cytologically confirmed, advanced, relapsed or metastatic gastric or gastroesophageal junction adenocarcinoma

• Patient must have one of the following diagnoses to be eligible for enrollment into cohorts:

  • Cohort 1: Checkpoint inhibitor naïve Epstein-Barr Virus negative (EBV-) gastric cancer patient who has had a disease progression after at least 2 prior systemic treatments for advanced or metastatic gastric cancer
  • Cohort 2: Checkpoint inhibitor naïve Epstein-Barr virus positive (EBV+) gastric cancer patient (as determined by standard methods, e.g. EBER ISH or LMP-1 IHC) who had at least 1 prior systemic treatment for advanced or metastatic gastric cancer
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Patient must have at least one measurable lesion at baseline by computed tomography(CT) or magnetic resonance imaging (MRI)
• Tumor available for biopsy

Exclusion Criteria:

• Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137), any history of discontinuing from that treatment due to Grade 3 or higher immune-related adverse event (irAE)
• Patient with MSI-H status
• Active autoimmune disease or serious autoimmune disease within past 2 years requiring systemic therapy
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, (non-infectious) pneumonitis that required steroids, or clinical symptoms of active pneumonitis
• Significant cardiovascular disease. New York Heart Association (NYHA) Class 3 or 4 congestive heart failure, or chronic Grade 3 hypertension.
• Significant screening electrocardiogram (ECG) abnormalities
• Has had an allogenic tissue/solid organ transplant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: FLX475 and pembrolizumab combination therapy; Cohort 1: EBV negative / CPI naïve gastric cancer patient who has had a disease progression after at least 2 prior systemic treatments for advanced or metastatic gastric cancer; Cohort 2: EBV positive / CPI naïve gastric cancer patient (as determined by standard methods, e.g. EBER ISH or LMP-1 IHC) who had at least 1 prior systemic treatment for advanced or metastatic gastric cancer

Drug: Pembrolizumab; IV infusion; Other Names: KEYTRUDA®; Drug: FLX475; tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) in Subjects Treated With FLX475 in Combination With Pembrolizumab	The primary efficacy endpoint is Objective Response Rate (ORR) defined as the proportion of subjects whose confirmed best overall response is either Complete Response (CR) or Partial Response (PR) according to RECIST version 1.1. For the efficacy endpoints (such as ORR and DCR), frequency and percentage of subjects who have achieved a response will be summarized by cohort and 95% 2-sided confidence interval will be calculated by Clopper-Pearson method.	Initial assessment performed after the first 2 cycles, then every 2 cycles for the first year, followed by every 3 cycles thereafter for up to 2 years and at any time per investigator's discretion and at ED/EOT, up to 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR) in Subjects Treated With FLX475 in Combination With Pembrolizumab	The Disease Control Rate (DCR) is defined as the proportion of subjects with confirmed best overall response of CR, PR or SD according to RECIST version 1.1.	Initial assessment performed after the first 2 cycles, then every 2 cycles for the first year, followed by every 3 cycles thereafter for up to 2 years and at any time per investigator's discretion and at ED/EOT, up to 2 years.
Time to Response (TTR) in Subjects Treated With FLX475 in Combination With Pembrolizumab	The Time to Response (TTR) is defined as the time from the date of first administration of study treatment to first documented Complete Response (CR) or Partial Response (PR).	Initial assessment performed after the first 2 cycles, then every 2 cycles for the first year, followed by every 3 cycles thereafter for up to 2 years and at any time per investigator's discretion and at ED/EOT, up to 2 years.
Duration of Response (DoR) in Subjects Treated With FLX475 in Combination With Pembrolizumab	The Duration of Response (DoR) is measured from the date of the first observation of tumor response (Complete Response (CR) or Partial Response (PR), whichever occurs first) to the date of disease progression or death for the subject with an objected response.	Initial assessment performed after the first 2 cycles, then every 2 cycles for the first year, followed by every 3 cycles thereafter for up to 2 years and at any time per investigator's discretion and at ED/EOT, up to 2 years.
Progression-free Survival (PFS) in Subjects Treated With FLX475 in Combination With Pembrolizumab	The Progression-free Survival (PFS) is defined as the time from the date of first administration of study treatment to determination of tumor progression by RECIST version 1.1 or death due to any cause, whichever occurs first.	Initial assessment performed after the first 2 cycles, then every 2 cycles for the first year, followed by every 3 cycles thereafter for up to 2 years and at any time per investigator's discretion and at ED/EOT, up to 2 years.
Overall Survival (OS) in Subjects Treated With FLX475 in Combination With Pembrolizumab	The Overall Survival (OS) is defined as the duration of time from the treatment start date to time to death from any cause. If subjects survive at the time of analysis, the subject will be censored at the last date of survival confirmed.	From baseline (Cycle 1 Day 1 prior to administration of the first study dose) until death from any cause.

Collaborators and Investigators

• Sponsor: Hanmi Pharmaceutical Company Limited
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2021
• Primary Completion (Actual): August 12, 2024
• Study Completion (Actual): August 12, 2024

Study Registration Dates

• First Submitted: February 22, 2021
• First Submitted That Met QC Criteria: February 22, 2021
• First Posted (Actual): February 24, 2021

Study Record Updates

• Last Update Posted (Estimated): September 25, 2025
• Last Update Submitted That Met QC Criteria: September 5, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; pembrolizumab
• Other Study ID Numbers: HM-CCRI-201; KEYNOTE-B83 (Other Identifier: Merck Sharp & Dohme LLC); MK-3475-B83 (Other Identifier: Merck Sharp & Dohme LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes