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
Overview
- Phase
- Phase 1
- Intervention
- Pamiparib
- Conditions
- Advanced High-grade Ovarian Cancer
- Sponsor
- BeiGene
- Enrollment
- 128
- Locations
- 6
- Primary Endpoint
- Phase 1: Number of Participants With Treatment- Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This study is designed to evaluate the safety, tolerability, PKharmacokinetic 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.
Investigators
Eligibility Criteria
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 triple-negative breast cancer or epithelial, non-mucinous, high-grade ovarian cancer (including fallopian cancer, or primary peritoneal cancer), for which no effective standard therapy is available.
- •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.
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
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.
Arms & Interventions
Phase 1: 20 milligram (mg) pamiparib
20 mg pamiparib twice a day for 21 days
Intervention: Pamiparib
Phase 1 : 40 mg pamiparib
40 mg pamiparib twice a day for 21 days
Intervention: Pamiparib
60 mg pamiparib
60 mg pamiparib twice a day for 21 days
Intervention: Pamiparib
60 mg pamiparib in platinum-sensitive ovarian cancer (PSOC)
60 mg pamiparib twice a day until occurrence of unacceptable toxicities, disease progression, withdrawal of consent or investigator discretion
Intervention: Pamiparib
60 mg pamiparib in platinum resistant ovarian cancer (PROC)
60 mg pamiparib twice a day until occurrence of unacceptable toxicities, disease progression, withdrawal of consent or investigator discretion
Intervention: Pamiparib
Outcomes
Primary Outcomes
Phase 1: Number of Participants With Treatment- Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)
Time Frame: From first dose to within 30 days of last dose of pamiparib (approximately 36 months)
A TEAE is defined as an adverse event (AE) that had an onset date on or after the first dose of study drug up to 30 days following study drug discontinuation or was worsening in severity from baseline (pretreatment).
Phase 1: Number of Participants With Clinically Significant Abnormalities in Physical Examinations and Electrocardiograms (ECGs)
Time Frame: From first dose to within 30 days of last dose of pamiparib (approximately 36 months)
Phase 2: Objective Response Rate (ORR) in High Grade Ovarian Cancer (HGOC) Both PSOC and PROC as Assessed by Independent Radiology Review Committee (IRC)
Time Frame: Up to approximately 2 years and 8 months
ORR is defined as the percentage of participants with confirmed Complete Response or Partial Response
Secondary Outcomes
- Phase 2: Area Under the Plasma Concentration-time Curve From 0 to 12 Hours Post-dose (AUC0-12)(Cycle 1 Day 1 and Cycle 2 Day 1: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose)
- Phase I: Maximum Observed Plasma Concentration (Cmax)(Cycle 1 Day 1 and Day 10 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose)
- Phase I: Terminal Elimination Half-life (t1/2)(Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose)
- Phase I: Time to Reach Cmax (Tmax)(Cycle 1 Day 1 and Day 10 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose)
- Phase I: Apparent Clearance (CL/F)(Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose)
- Phase 1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUCinf)(Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose)
- Phase I: Apparent Volume of Distribution During Terminal Phase (Vz/F)(Cycle 1 Day 1 of 21-day cycle: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose)
- Phase 2: Disease Control Rate by Investigator Per RECIST v1.1(Up to approximately 3 years and 8 months)
- Phase 2: Duration of Response as Assessed by Investigator Per RECIST v1.1(Up to approximately 3 years and 8 months)
- Phase 1: Disease Control Rate (DCR) Assessed by the Investigator Per RECIST v1.1(Up to approximately 36 months)
- Phase I: Clinical Benefit Rate (CBR) Assessed by the Investigator Per RECIST v1.1(Up to approximately 36 months)
- Phase I : Progression Free Survival (PFS)(Up to approximately 36 months)
- Phase 2: Carcinoma Antigen-125 (C(A-125) Response Rate by Gynecologic Cancer Inter Group (GCIG )Criteria(Up to approximately 3 years and 8 months)
- Phase 2: Number of Participants With Treatment- Emergent Adverse Events and Serious Adverse Events(From first dose to within 30 days of last dose of pamiparib (approximately 3 years and 8 months))
- Phase 2: Maximum Observed Plasma Concentration (Cmax)(Cycle 1 Day 1 and Cycle 2 Day 1: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose)
- Phase I: Confirmed Objective Response Rate (ORR) as Assessed by the Investigator Per RECIST v1.1(Up to approximately 36 months)
- Phase 1: Duration of Response (DOR) as Assessed by Investigator Per RECIST v1.1(Up to approximately 36 months)
- Phase 2: Objective Response Rate (ORR) by Investigator Per RECIST v1.1(Up to approximately 3 years and 8 months)
- Phase 2: Clinical Benefit Rate by Investigator Per RECIST v1.1(Up to approximately 3 years and 8 months)
- Phase 2: Overall Survival (OS) as Assessed by Investigator(Up to approximately 3 years and 8 months)
- Phase 2: Time to Reach Cmax (Tmax)(Cycle 1 Day 1 and Cycle 2 Day 1: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose)
- Phase 2: Progression Free Survival as Assessed by the Investigator Per RECIST v1.1(Up to approximately 3 years and 8 months)
- Phase 2: Area Under the Plasma Concentration-time Curve From 0 to the 9 Hours Post-dose (AUC0-9)(Cycle 1 Day 1 and Cycle 2 Day 1: pre-dose, 0.5, 1, 2, 4, 6,9 and 12 hours post dose)