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

Hanmi Pharmaceutical Company Limited20 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Gastric Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (10)

Hanllym University Medical Center

Anyang-si, Gyeonggi-do, South Korea

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, South Korea

The Catholic University of Korea St. Vincent Hospital

Suwon, Gyeonggi-do, South Korea

Chonnam National University Hwasun Hospital

Hwasun, Jeollanam-do, South Korea

Asan Medical Center

Seoul, South Korea

Gangnam Severance Hospital

Seoul, South Korea

Korea University Guro Hospital

Seoul, South Korea

Samsung Medical Center

Seoul, South Korea

Seoul National University Hospital

Seoul, South Korea

Severance Hospital

Seoul, South Korea

Outcomes

Primary Outcomes

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.

Time frame: 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

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.

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).

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.

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.

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.

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