Study of BGB-290 or Placebo in Participants With Advanced or Inoperable Gastric Cancer

Study Overview
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Brief Summary
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This study enrolled participants with previously-treated advanced or inoperable gastric cancer who have responded to first line platinum therapy into two treatment arms. In Arm A participants received BGB-290; in Arm B participants received placebo. The purpose of this study is to show that BGB-290 (pamiparib) (versus placebo) will improve progression-free survival (PFS) in participants with advanced or inoperable gastric cancer.

Detailed Description
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This is a double-blind, placebo controlled, randomized multicenter global phase 2 study comparing the efficacy and safety of single agent poly (ADP-ribose) polymerase (PARP) inhibitor BGB-290 to placebo as maintenance therapy in participants with advanced gastric cancer who have responded to first line platinum based chemotherapy. Participants are randomized 1:1 to BGB-290 (Arm A) or placebo (Arm B). Randomization will be stratified by geography, biomarker status, and ECOG performance status. Participants will undergo tumor assessments at screening and then every 8 weeks, or as clinically indicated. Administration of BGB-290 or placebo will continue until disease progression, unacceptable toxicity, death, or another discontinuation criterion is met. After end of treatment, long-term follow-up assessments include tumor imaging every 8 weeks for those participants without disease progression, survival status, and new anticancer therapy.

Official Title
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A Phase 2, Double-blind, Randomized Study of BGB-290 Versus Placebo as Maintenance Therapy in Patients With Inoperable Locally Advanced or Metastatic Gastric Cancer That Responded to Platinum-based First-line Chemotherapy

Conditions
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Advanced or Inoperable Gastric Cancer

Intervention / Treatment
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* Drug: Pamiparib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Age ≥ 18 years. Signed informed consent. Histologically confirmed inoperable locally advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. Received platinum based first line chemotherapy for ≤ 28 weeks. Confirmed partial response (PR) maintained for ≥ 4 weeks or complete response (CR). Able to be randomized to study ≤ 8 weeks after last platinum dose. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1. Adequate hematologic, renal and hepatic function. Must be able to provide archival tumor tissue for central biomarker assessment. Females of childbearing potential and non-sterile males must agree to use highly effective methods of birth control throughout the course of study and at least up to 6 months after last dosing. Key Exclusion Criteria: Unresolved acute effects of prior therapy ≥ Grade 2. Prior treatment with PARP inhibitor. Chemotherapy, biologic therapy, immunotherapy or other anticancer therapy ≤ 14 days prior to randomization. Major surgery or significant injury ≤ 2 weeks prior to start of study treatment. Diagnosis of myelodysplastic syndrome (MDS) Other diagnoses of significant malignancy Leptomeningeal disease or brain metastasis Inability to swallow capsules or disease affecting gastrointestinal function. Active infections requiring systemic treatment. Clinically significant cardiovascular disease Pregnant or nursing females. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pamiparib<br>Participants received pamiparib orally. | Drug: Pamiparib<br>* 60 mg orally twice daily<br>* Other names: BGB-290;|
| Placebo Comparator: Placebo<br>Participants received placebo orally. | Drug: Placebo<br>* 60 mg orally twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) by Investigator Assessment | PFS is defined as the time from randomization to progressive disease (PD) per Response Evaluation Criteria in Solid Tumors ( RECIST) Version 1.1 by investigator assessment or death due to any cause, whichever occurs first. | Approximately 23 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is defined as the time from randomization to death due to any cause. | Approximately 23 months | 
| Time To Second Subsequent Treatment (TSST) | TSST is defined as the time from randomization until the second subsequent anticancer therapy or death after next-line therapy | Approximately 23 months | 
| Objective Response Rate (ORR) | ORR is defined as the percentage of participants with a best overall response of Complete Response or Partial Response per RECIST Version 1.1 by investigator assessment | Approximately 23 months | 
| Duration of Response (DOR) | DOR is defined as the time from the first documented confirmed response of Complete Response or Partial Response to progressive disease (PD) per RECIST Version 1.1 by investigator assessment or death due to any cause, whichever occurs first | Approximately 23 months | 
| Time To Response | Time to response is defined as the time from randomization to the first documented response of Complete Response or Partial Response per RECIST Version 1.1 by investigator assessment | Approximately 23 months | 
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |  | From start of study treatment until 30 days after the last study drug intake or initiation of new anticancer therapy, whichever occurs first (up to approximately 4 years and 5.5 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BGB-290, PARP inhibitor, Phase 2, maintenance therapy, gastric cancer, oral treatment, PARALLEL 303, PARALLEL, BGB290303, BGB-290-303