Study to Assess Safety, Tolerability and Clinical Activity of BGB-290 in Combination With Temozolomide (TMZ) in Participants With Locally Advanced or Metastatic Solid Tumors
- Conditions
- Locally Advanced or Metastatic Solid Tumors
- Interventions
- Registration Number
- NCT03150810
- Lead Sponsor
- BeiGene
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 139
-
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
Key
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 milligrams (mg) (Days 1-7) Pamiparib 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 Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 milligrams (mg) (Days 1-7) Temozolomide 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 Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7) Pamiparib 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 Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7) Temozolomide 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 Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7) Pamiparib 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 Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7) Temozolomide 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 Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7) Pamiparib 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 Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7) Temozolomide 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 Dose Escalation: Pamiparib + TMZ 120 mg (Days 1-7) Pamiparib 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 Dose Escalation: Pamiparib + TMZ 120 mg (Days 1-7) Temozolomide 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 Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-14) Pamiparib 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 Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-14) Temozolomide 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 Dose Escalation: Pamiparib + TMZ 20 mg (Days 1-28) Pamiparib 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 Dose Escalation: Pamiparib + TMZ 20 mg (Days 1-28) Temozolomide 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 Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-28) Pamiparib 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 Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-28) Temozolomide 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 Dose Expansion: Gastric Cancer Pamiparib 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 Dose Expansion: Gastric Cancer Temozolomide 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 Dose Expansion: Ovarian Cancer Pamiparib 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 Dose Expansion: Ovarian Cancer Temozolomide 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 Dose Expansion: SCLC Pamiparib 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 Dose Expansion: SCLC Temozolomide 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 Dose Expansion: TNBC Pamiparib 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 Dose Expansion: TNBC Temozolomide 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 Dose Expansion: Other HRD+ Cancers Pamiparib 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 Dose Expansion: Other HRD+ Cancers Temozolomide 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
- Primary Outcome Measures
Name Time Method Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs) 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) 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) 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.
- Secondary Outcome Measures
Name Time Method 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) Pamiparib pharmakokinetic (PK) parameters were assessed in the first 20 participants enrolled in the dose escalation phase after a single dose on Day -2 and at steady state in combination with TMZ on Day 15.
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 DCR is defined as the percentage of participants with BOR of CR, PR, or stable disease (SD) based on investigator assessment using RECIST v1.1.
Duration of Response (DOR) Up to approximately 5 years and 10 months DOR is defined as the time from the date of the earliest documented CR or PR (that is subsequently confirmed) to disease progression or death due to any cause, whichever occurs earlier, based on investigator assessment using RECIST v1.1. Only responders will be included in the assessment.
Progression Free Survival (PFS) Up to approximately 5 years and 10 months) PFS is defined as the time (months) from the date of the first dose of combination treatment to disease progression or death due to any cause, whichever occurs first, based on investigator assessment using RECIST v1.1
Overall Survival (OS) Up to approximately 5 years and 10 months OS is defined as the time from the date of the first dose of combination treatment to death due to any cause.
Trial Locations
- Locations (22)
Start Midwest
🇺🇸Grand Rapids, Michigan, United States
Washington University in St Louis
🇺🇸Saint Louis, Missouri, United States
Montefiore Medical Park At Eastchester Einstein Campus
🇺🇸Bronx, New York, United States
Mount Sinai Prime
🇺🇸New York, New York, United States
Sarah Cannon Cancer Center
🇺🇸Nashville, Tennessee, United States
Texas Oncology (Loop) Usor
🇺🇸Dallas, Texas, United States
The University of Texas Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
Chris Obrien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Saint Vincents Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
Peter Maccallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Hospital Universitario Vall Dhebron
🇪🇸Barcelona, Spain
Ico H Duran I Reynals
🇪🇸Barcelona, Spain
Hospital Universitario Ramon Y Cajal
🇪🇸Madrid, Spain
Start Madrid Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Spain
Hospital Universitario Virgen de La Macarena
🇪🇸Sevilla, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Northern Centre For Cancer Care
🇬🇧High Heaton, United Kingdom
University College Hospital
🇬🇧London, United Kingdom
Sarah Cannon Research Institute Uk
🇬🇧London, United Kingdom
Icon Cancer Centre South Brisbane
🇦🇺South Brisbane, Queensland, Australia
Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom