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

Phase 2

Completed

Conditions: Gastric Cancer

Interventions: Drug: FLX475
Drug: Pembrolizumab

Registration Number: NCT04768686

Lead Sponsor: Hanmi Pharmaceutical Company Limited

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
FLX475 and pembrolizumab combination therapy	Pembrolizumab	* 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
FLX475 and pembrolizumab combination therapy	FLX475	* 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

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR) 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.	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.

Secondary Outcome Measures

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

Trial Locations

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
Hanllym University Medical Center
🇰🇷Anyang-si, Gyeonggi-do, South Korea