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

NCT04768686 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: HM-CCRI-201KEYNOTE-B83MK-3475-B83
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Disease Control Rate (DCR) in Subjects Treated With FLX475 in Combination With Pembrolizumab

  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

  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

  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

  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

  From baseline (Cycle 1 Day 1 prior to administration of the first study dose) until death from any cause.

Study Arms (1)

FLX475 and pembrolizumab combination therapy

EXPERIMENTAL

* 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: FLX475; Drug: Pembrolizumab

Interventions

FLX475 DRUG

tablet

FLX475 and pembrolizumab combination therapy

Pembrolizumab DRUG

IV infusion

Also known as: KEYTRUDA®

FLX475 and pembrolizumab combination therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hanmi Pharmaceutical Company Limited: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (10)

Hanllym University Medical Center

Anyang-si, Gyeonggi-do, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

Location

The Catholic University of Korea St. Vincent Hospital

Suwon, Gyeonggi-do, South Korea

Location

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Gangnam Severance Hospital

Seoul, South Korea

Location

Korea University Guro Hospital

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Results Point of Contact

• Title: Young Su (Bobby) Noh
• Organization: Hanmi Pharm. Co., Ltd.

63forever@hanmi.co.kr

82-2-410-9277

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2021
• First Posted: February 24, 2021
• Study Start: May 18, 2021
• Primary Completion: August 12, 2024
• Study Completion: August 12, 2024
• Last Updated: September 25, 2025
• Results First Posted: September 25, 2025

Record last verified: 2025-09

Locations

KR (10)