Study of the Efficacy, Safety and Pharmacokinetics of Pamiparib (BGB-290) in Participants With Advanced Solid Tumors

Study Overview
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Brief Summary
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This study is designed to evaluate the safety, tolerability, PK profile and treatment effect of pamiparib in Chinese participants with advanced high-grade ovarian cancer (including fallopian cancer or primary peritoneal cancer) and triple negative breast cancer in phase I, and to evaluate the efficacy and safety of pamiparib in Chinese participants with recurrent epithelial ovarian cancer (including fallopian cancer or primary peritoneal cancer), harboring germline breast cancer susceptibility gene 1/gene 2 (BRCA1/2) mutation in phase II.

Official Title
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An Open Label, Multi-Center Phase I/II Study to Evaluate Efficacy and Safety of BGB-290 in Chinese Subjects With Advanced Ovarian Cancer, Fallopian Cancer, and Primary Peritoneal Cancer or Advanced Triple Negative Breast Cancer

Conditions
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Advanced High-grade Ovarian Cancer, Triple Negative Breast Cancer

Intervention / Treatment
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* Drug: Pamiparib


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participants have voluntarily agreed to participate by giving written informed consent. Age 18 years (including 18 years) on the day of signing informed consent. Participants meet the following eligibility criteria for the corresponding part of the study: 1) In Phase 1 portion: The participants must have a histologically or cytologically confirmed locally advanced or metastatic cancer, either TNBC or epithelial, non-mucinous, HGOC (including fallopian cancer, or primary peritoneal cancer), for which no effective standard therapy is available. 2) In Phase 2 portion: Participants who have histologically or cytologically confirmed high-grade epithelial ovarian cancer (including fallopian cancer or primary peritoneal cancer), harboring germline BRCA1/2 mutation Participants must have measurable disease as defined per the RECIST, version 1.1. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 Key Exclusion Criteria: Participants who have been treated with chemotherapy, biologic therapy, immunotherapy, investigational agent, anti-cancer Chinese medicine, or anticancer herbal remedies ≤ 14 days (or ≤5 half-lives, whichever is shorter) prior to starting study drug, or who have not adequately recovered from the side effects of such therapy. Participants who have undergone major surgery for any cause ≤ 4 weeks prior to starting study drug. Participants must have adequately recovered from the previous treatment and have a stable clinical condition before entering the study. Participants who have undergone radiotherapy for any cause ≤ 14 days prior to starting study drug. Participants must have adequately recovered from the previous treatment and have a stable clinical condition before entering the study. Untreated and/or active brain metastases. Prior therapies targeting poly (ADP-ribose) polymerase (PARP). 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-grade ovarian cancer and triple negative breast cancer<br> | Drug: Pamiparib<br>* Pamiparib is provided as oral capsules，Three dose levels will be evaluated as 20mg, 40mg, 60mg separately， twice a day in phase I and will be used with single dose based on RP2D in phase II.<br>* Other names: BGB-290;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I:Number of participants with treatment-related adverse events assessed by NCI-CTCAE v4.03 Phase II: Objective response rate |  | Phase I:From first dose to within 30 days of last dose of BGB-290 (pamiparib) | 
| Phase II: Objective response rate by RECIST v1.1 |  | From first dose of BGB-290 to the first documented disease progression or death due to any cause, whichever came first，, assessed up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Objective response rate, disease control rate and clinical benefit rate by RECIST v1.1 |  | Every 6 weeks from first dose until the date of first documented progression or date of death from any cause, whichever came first，assessed up to 5 years | 
| Phase I: Duration of response by RECIST v1.1 |  | Every 6 weeks from first dose until the date of first documented progression or date of death from any cause, whichever came first，assessed up to 5 years | 
| Phase I：Progression free survival |  | From first dose of BGB-290 to the first documented disease progression or death due to any cause, whichever came first，assessed up to 5 years | 
| Phase I: Area under the plasma concentration-time curve from 0 to the last measurable concentration (AUClast) |  | During first 7 weeks | 
| Phase I: Maximum observed plasma concentration (Cmax) |  | During first 7 weeks | 
| Phase I: Time to reach Cmax (Tmax) |  | During first 7 weeks | 
| Phase I: Terminal elimination half-life (t1/2) |  | During first 7 weeks | 
| Phase I: Apparent clearance (CL/F) |  | During first 7 weeks | 
| Phase I: Apparent volume of distribution during terminal phase (Vz/F） |  | During first 7 weeks | 
| Phase II: Disease control rate and clinical benefit rate by RECIST v1.1 and CA125 response rate by GCIG criteria |  | Every 6 weeks from first dose until the date of first documented progression or date of death from any cause, whichever came first，assessed up to 5 years | 
| Phase II: Duration of response by RECIST v1.1 |  | Every 6 weeks from first dose until the date of first documented progression or date of death from any cause, whichever came first，assessed up to 5 years | 
| Phase II: Progression free survival |  | From first dose of BGB-290 to the first documented disease progression or death due to any cause, whichever came first，assessed up to 5 years | 
| Phase II: Overall survival |  | From first dose of BGB-290 to death due to any cause，assessed up to 5 years | 
| Phase II: Number of participants with treatment-related adverse events assessed by NCI-CTCAE v4.03 |  | From first dose to within 30 days of last dose of BGB-290 | 
| Phase II: Pharmacokinetics parameters as mentioned above for selected participants |  | During first 7 weeks |