A Phase 1b Study to Assess the Safety, Tolerability and Clinical Activity of BGB-290 in Combination With Temozolomide (TMZ) in Subjects With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 139
- 试验地点
- 22
- 主要终点
- Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The primary objective of this study was to determine the safety and tolerability of pamiparib, the maximum tolerated dose (MTD) or maximum administered dose (MAD) for pamiparib combined with TMZ, to select the recommended Phase 2 dose (RP2D) and schedule of pamiparib in combination with TMZ, and to determine the antitumor activity of pamiparib in combination with TMZ.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years old with advanced or metastatic stage solid tumors
- •Eastern Cooperative Oncology Group (ECOG) status ≤ 1
- •Have disease either evaluable (dose-escalation cohort) or measurable (dose-escalation and -expansion cohorts) per RECIST V1.1, except for prostate cancer participants
- •Agree to provide archival tumor tissue
- •Additional inclusion criteria for dose expansion cohorts:
- •Participants with homologous recombination deficiency (HRD+) or known BRCA mutant ovarian cancer Previously received at least one line of platinum-containing therapy in the advanced or metastatic setting and No progression or recurrent disease within 6 months from last platinum-containing regimen.
- •Participants with HRD+ or known BRCA mutant triple-negative breast cancer Up to one prior platinum-containing treatment in any treatment setting and up to 3 prior lines of therapy in the advanced or metastatic setting
- •Participants with HRD+ or known BRCA mutant prostate cancer Chemotherapy-naïve or previously received up to two taxane-based chemotherapy regimens, with documented prostate cancer progression
- •Participants with small cell lung cancer and gastric cancer, previously received ≤ 2 prior lines of therapy
- •Other HRD+ solid tumors of multiple indications
排除标准
- •All participants
- •Prior treatment with a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor.
- •Refractory to platinum-based therapy (dose-expansion cohort).
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 milligrams (mg) (Days 1-7)
Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 7 within a 28-day cycle
干预措施: Pamiparib (Drug)
Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 milligrams (mg) (Days 1-7)
Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 7 within a 28-day cycle
干预措施: Temozolomide (Drug)
Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7)
Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 60 mg once daily on Days 1 to 7 within a 28-day cycle
干预措施: Pamiparib (Drug)
Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7)
Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 60 mg once daily on Days 1 to 7 within a 28-day cycle
干预措施: Temozolomide (Drug)
Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7)
Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 80 mg once daily on Days 1 to 7 within a 28-day cycle
干预措施: Pamiparib (Drug)
Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7)
Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 80 mg once daily on Days 1 to 7 within a 28-day cycle
干预措施: Temozolomide (Drug)
Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7)
Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 100 mg once daily on Days 1 to 7 within a 28-day cycle
干预措施: Pamiparib (Drug)
Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7)
Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 100 mg once daily on Days 1 to 7 within a 28-day cycle
干预措施: Temozolomide (Drug)
Dose Escalation: Pamiparib + TMZ 120 mg (Days 1-7)
Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 120 mg once daily on Days 1 to 7 within a 28-day cycle
干预措施: Pamiparib (Drug)
Dose Escalation: Pamiparib + TMZ 120 mg (Days 1-7)
Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 120 mg once daily on Days 1 to 7 within a 28-day cycle
干预措施: Temozolomide (Drug)
Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-14)
Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 14 within a 28-day cycle
干预措施: Pamiparib (Drug)
Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-14)
Pamiparib 60 mg twice daily on Days 1 to 28 in combination with pulse dosing of TMZ 40 mg once daily on Days 1 to 14 within a 28-day cycle
干预措施: Temozolomide (Drug)
Dose Escalation: Pamiparib + TMZ 20 mg (Days 1-28)
Pamiparib 60 mg twice daily in combination with TMZ 20 mg once daily administered continuously on Days 1 to 28 within a 28-day cycle
干预措施: Pamiparib (Drug)
Dose Escalation: Pamiparib + TMZ 20 mg (Days 1-28)
Pamiparib 60 mg twice daily in combination with TMZ 20 mg once daily administered continuously on Days 1 to 28 within a 28-day cycle
干预措施: Temozolomide (Drug)
Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-28)
Pamiparib 60 mg twice daily in combination with TMZ 40 mg once daily administered continuously on Days 1 to 28 within a 28-day cycle
干预措施: Pamiparib (Drug)
Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-28)
Pamiparib 60 mg twice daily in combination with TMZ 40 mg once daily administered continuously on Days 1 to 28 within a 28-day cycle
干预措施: Temozolomide (Drug)
Dose Expansion: Gastric Cancer
Participants with gastric or gastroesophageal junction cancer received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle
干预措施: Pamiparib (Drug)
Dose Expansion: Gastric Cancer
Participants with gastric or gastroesophageal junction cancer received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle
干预措施: Temozolomide (Drug)
Dose Expansion: Ovarian Cancer
Participants with ovarian cancer, fallopian cancer, or primary peritoneal cancer received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle
干预措施: Pamiparib (Drug)
Dose Expansion: Ovarian Cancer
Participants with ovarian cancer, fallopian cancer, or primary peritoneal cancer received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle
干预措施: Temozolomide (Drug)
Dose Expansion: SCLC
Participants with Small Cell Lung Cancer (SCLC) received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle
干预措施: Pamiparib (Drug)
Dose Expansion: SCLC
Participants with Small Cell Lung Cancer (SCLC) received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle
干预措施: Temozolomide (Drug)
Dose Expansion: TNBC
Participants with triple negative breast cancer (TNBC) received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle
干预措施: Pamiparib (Drug)
Dose Expansion: TNBC
Participants with triple negative breast cancer (TNBC) received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle
干预措施: Temozolomide (Drug)
Dose Expansion: Other HRD+ Cancers
Participants with non-small cell lung cancer (NSCLC), esophageal cancer, squamous head and neck cancer, or soft tissue sarcomas whose tumors are homologous recombination deficiency (HRD)+ received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle
干预措施: Pamiparib (Drug)
Dose Expansion: Other HRD+ Cancers
Participants with non-small cell lung cancer (NSCLC), esophageal cancer, squamous head and neck cancer, or soft tissue sarcomas whose tumors are homologous recombination deficiency (HRD)+ received TMZ 60 mg administered on Days 1 to 7 in combination with pamiparib 60 mg twice daily on Days 1 to 28 of each cycle
干预措施: Temozolomide (Drug)
结局指标
主要结局
Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: From first dose of study drug(s) to 28 days post-dose (up to approximately 1 year and 6 months)
A DLT is defined as one of the following toxicities occurring during the DLT assessment window: Grade ≥3 non-hematologic, non-hepatic major organ adverse event (AE) Grade 4 neutropenia lasting \>7 days Grade ≥3 febrile neutropenia Grade 3 thrombocytopenia with clinically significant bleeding Grade 4 thrombocytopenia lasting \> 3 days and requiring transfusion, or any decreased platelet count \<15,000/mm3/ \<15.0 x 109/L Grade ≥4 anemia Grade ≥3 total bilirubin or hepatic transaminases (ALT or AST)
Number of Participants Experiencing Adverse Events (AEs)
时间窗: From the first dose of study drug(s) to 30 days after the last dose; up to approximately 5 years and 10 months
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory values, vital signs, physical examination findings, and electrocardiogram results, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v4.03
Objective Response Rate (ORR)
时间窗: Up to approximately 5 years and 10 months
ORR is defined as the percentage of participants who have a best overall response (BOR) of complete response (CR) or partial response (PR) based on investigator assessment using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, where BOR is defined as the best response recorded from the first postbaseline tumor assessment until data cutoff date, disease progression or start of new anticancer treatment.
次要结局
- Maximum Observed Plasma Concentration (Cmax) of Pamiparib(2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing, and on Cycle 1 Day 15 at predose, 1, 2, and 4 hours postdose (each cycle is 28 days))
- Plasma Trough Concentrations of Pamiparib (Ctrough)(Cycle 1 Day 15 predose)
- Time to Reach Cmax (Tmax) of Pamiparib(2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing, and on Cycle 1 Day 15 at predose, 1, 2, and 4 hours postdose.)
- Area Under the Curve From Time 0 to 4 Hours (AUC0-4h) of Pamiparib(2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, and 4 hours after dosing, and on Cycle 1 Day 15 at predose, 1, 2, and 4 hours postdose.)
- Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Pamiparib(2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing)
- Terminal Elimination Half-life (t1/2) of Pamiparib(2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing (each cycle is 28 days))
- Apparent Clearance (CL/F) of Pamiparib(2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing (each cycle is 28 days))
- Apparent Volume of Distribution During Terminal Phase (Vz/F) of Pamiparib(2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing (each cycle is 28 days))
- Plasma Concentration of Temozolomide (TMZ)(Predose (within 30 min prior to dose) and 1 hour post dose on Cycle 1 Day 1 and Cycle 1 Day 7)
- Disease Control Rate (DCR)(Up to approximately 5 years and 10 months)
- Duration of Response (DOR)(Up to approximately 5 years and 10 months)
- Progression Free Survival (PFS)(Up to approximately 5 years and 10 months))
- Overall Survival (OS)(Up to approximately 5 years and 10 months)