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

Study Overview
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Brief Summary
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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.

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

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: FLX475
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FLX475 and pembrolizumab combination therapy<br>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<br>* tablet<br>Drug: Pembrolizumab<br>* IV infusion<br>* Other names: Keytruda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate in subjects treated with FLX475 in combination with pembrolizumab |  | Through study completion (approximately 2 years) |