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

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

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.

Study Overview

• Status: Completed
• Conditions: Triple Negative Breast Cancer; Advanced High-grade Ovarian Cancer
• Intervention / Treatment: Drug: Pamiparib

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230001
      • Anhui Provincial Cancer Hospital
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University First Hospital
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing, China, 100021
      • Cancer Hospital Chinese Academy of Medical Sciences
    • Beijing, Beijing, China, 100032
      • Peking Union Medical College Hospital
    • Beijing, Beijing, China, 100034
      • Peking University People Hospital
  • Changchun
    • Jilin, Changchun, China, 130021
      • The First Bethune Hospital of Jilin University
  • Chongqing
    • Chongqing, Chongqing, China, 400030
      • Chongqing Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 528400
      • Sun Yat-sen Memorial Hospital,Sun Yat-sen University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430079
      • Hubei Cancer Hospital
    • Wuhan, Hubei, China, 430030
      • Union Hospital Tongji Medical College Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410006
      • Hunan Cancer Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Province Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Jiangxi Maternal and Child Health Hospital
  • Jilin
    • Changchun, Jilin, China, 130022
      • The Second Hospital of Jilin University
    • Changchun, Jilin, China, 130021
      • Jilin cancer hospital
  • Liaoning
    • Dalian, Liaoning, China, 116044
      • The First Hospital of Dalian Medical University
    • Dalian, Liaoning, China, 215000
      • The First Affiliated Hospital of Xian Jiaotong University
    • Shenyang, Liaoning, China, 110042
      • Liaoning Cancer Hospital&Institute
  • Shandong
    • Jinan, Shandong, China, 250012
      • Qilu Hospital of Shandong University
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300070
      • Tianjin Medical University Cancer Institute & Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Participants have voluntarily agreed to participate by giving written informed consent.
2. Age 18 years (including 18 years) on the day of signing informed consent.
3. 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.

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 4. Participants must have measurable disease as defined per the RECIST, version 1.1.

5. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1

Key Exclusion Criteria:

1. 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.
2. 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.
3. 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.
4. Untreated and/or active brain metastases.
5. Prior therapies targeting poly (ADP-ribose) polymerase (PARP).

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: 20 milligram (mg) pamiparib; 20 mg pamiparib twice a day for 21 days	Drug: Pamiparib; Pamiparib is provided as oral capsules; Other Names: BGB-290
Experimental: Phase 1 : 40 mg pamiparib; 40 mg pamiparib twice a day for 21 days	Drug: Pamiparib; Pamiparib is provided as oral capsules; Other Names: BGB-290
Experimental: 60 mg pamiparib; 60 mg pamiparib twice a day for 21 days	Drug: Pamiparib; Pamiparib is provided as oral capsules; Other Names: BGB-290
Experimental: 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	Drug: Pamiparib; Pamiparib is provided as oral capsules; Other Names: BGB-290
Experimental: 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	Drug: Pamiparib; Pamiparib is provided as oral capsules; Other Names: BGB-290

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Number of Participants With Treatment- Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)	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).	From first dose to within 30 days of last dose of pamiparib (approximately 36 months)
Phase 1: Number of Participants With Clinically Significant Abnormalities in Physical Examinations and Electrocardiograms (ECGs)		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)	ORR is defined as the percentage of participants with confirmed Complete Response or Partial Response	Up to approximately 2 years and 8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: 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: 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: 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 I: Confirmed Objective Response Rate (ORR) as Assessed by the Investigator Per RECIST v1.1	ORR is defined as the percentage of participants with confirmed Complete Response (CR) or Partial Response (PR)	Up to approximately 36 months
Phase 1: Disease Control Rate (DCR) Assessed by the Investigator Per RECIST v1.1	DCR is defined as the percentage of participants with best overall response (BOR) of CR, PR and stable disease (SD)	Up to approximately 36 months
Phase I: Clinical Benefit Rate (CBR) Assessed by the Investigator Per RECIST v1.1	CBR is defined as percentage of participants with best overall response of CR, PR and stable disease (SD)≥24 weeks	Up to approximately 36 months
Phase 1: Duration of Response (DOR) as Assessed by Investigator Per RECIST v1.1	DOR is defined as the time from the first determination of a confirmed overall response until the first documentation of progression or death, whichever comes first	Up to approximately 36 months
Phase I : Progression Free Survival (PFS)	PFS is defined as the time from first dose of study medication to the first documented disease progression or death due to any cause, whichever occurs first	Up to approximately 36 months
Phase 2: Objective Response Rate (ORR) by Investigator Per RECIST v1.1	ORR is defined as the percentage of participants with confirmed Complete Response or Partial Response	Up to approximately 3 years and 8 months
Phase 2: Disease Control Rate by Investigator Per RECIST v1.1	DCR is defined as the percentage of participants with best overall response (BOR) of CR, PR and stable disease (SD)	Up to approximately 3 years and 8 months
Phase 2: Clinical Benefit Rate by Investigator Per RECIST v1.1	CBR is defined as percentage of participants with best overall response of CR, PR and stable disease (SD)≥24 weeks	Up to approximately 3 years and 8 months
Phase 2: Carcinoma Antigen-125 (C(A-125) Response Rate by Gynecologic Cancer Inter Group (GCIG )Criteria	CA-125 response is defined the percentage of participants with at least 50% reduction in CA-125 levels from pre-treatment sample	Up to approximately 3 years and 8 months
Phase 2: Duration of Response as Assessed by Investigator Per RECIST v1.1	DOR is defined as the time from the first determination of a confirmed overall response until the first documentation of progression or death, whichever comes first	Up to approximately 3 years and 8 months
Phase 2: Progression Free Survival as Assessed by the Investigator Per RECIST v1.1	PFS is defined as the time from first dose of study medication to the first documented disease progression or death due to any cause, whichever occurs first	Up to approximately 3 years and 8 months
Phase 2: Overall Survival (OS) as Assessed by Investigator	OS is defined as time from the first dose of study medication to the date of death due to any cause	Up to approximately 3 years and 8 months
Phase 2: Number of Participants With Treatment- Emergent Adverse Events and Serious Adverse Events	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). All clinically significant abnormalities in physical examinations, laboratory tests and ECGs are reported as adverse events (AE) in the AE section.	From first dose to within 30 days of last dose of pamiparib (approximately 3 years and 8 months)
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 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 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: 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

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Principal Investigator: Study Director, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2016
• Primary Completion (Actual): August 24, 2020
• Study Completion (Actual): August 11, 2021

Study Registration Dates

• First Submitted: November 1, 2017
• First Submitted That Met QC Criteria: November 2, 2017
• First Posted (Actual): November 7, 2017

Study Record Updates

• Last Update Posted (Estimated): February 22, 2024
• Last Update Submitted That Met QC Criteria: July 11, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Breast Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Breast Neoplasms; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Pamiparib
• Other Study ID Numbers: BGB-290-102; CTR20160828 (Registry Identifier: ChiCTR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No