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.
Brief Title
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
Categories
Completion Date
Completion Date Type
Actual
Conditions
Locally Advanced or Metastatic Solid Tumors
Eligibility Criteria
Key Inclusion Criteria:
1. Age ≥18 years old with advanced or metastatic stage solid tumors
2. Eastern Cooperative Oncology Group (ECOG) status ≤ 1
3. Have disease either evaluable (dose-escalation cohort) or measurable (dose-escalation and -expansion cohorts) per RECIST V1.1, except for prostate cancer participants
4. Agree to provide archival tumor tissue
5. 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 Exclusion Criteria: All participants
1. Prior treatment with a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor.
2. Refractory to platinum-based therapy (dose-expansion cohort).
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
1. Age ≥18 years old with advanced or metastatic stage solid tumors
2. Eastern Cooperative Oncology Group (ECOG) status ≤ 1
3. Have disease either evaluable (dose-escalation cohort) or measurable (dose-escalation and -expansion cohorts) per RECIST V1.1, except for prostate cancer participants
4. Agree to provide archival tumor tissue
5. 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 Exclusion Criteria: All participants
1. Prior treatment with a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor.
2. Refractory to platinum-based therapy (dose-expansion cohort).
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
Inclusion Criteria
Inclusion Criteria:
1. Age ≥18 years old with advanced or metastatic stage solid tumors
2. Eastern Cooperative Oncology Group (ECOG) status ≤ 1
3. Have disease either evaluable (dose-escalation cohort) or measurable (dose-escalation and -expansion cohorts) per RECIST V1.1, except for prostate cancer participants
4. Agree to provide archival tumor tissue
5. 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
Inclusion/
1. Age ≥18 years old with advanced or metastatic stage solid tumors
2. Eastern Cooperative Oncology Group (ECOG) status ≤ 1
3. Have disease either evaluable (dose-escalation cohort) or measurable (dose-escalation and -expansion cohorts) per RECIST V1.1, except for prostate cancer participants
4. Agree to provide archival tumor tissue
5. 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
Inclusion/
Gender
All
Gender Based
false
Keywords
Ovarian cancer
Triple negative breast cancer
Small cell lung cancer
Gastric cancer
temozolomide
BGB-290
antineoplastic agents
alkylating, alkylating agents,
Poly (ADP-ribose) polymerase inhibitors
enzyme inhibitors
Head and neck cancer
Esophageal cancer
Soft tissue sarcoma
Non small cell lung cancer
pamiparib
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03150810
Org Class
Industry
Org Full Name
BeiGene
Org Study Id
BGB-290-103
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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
Primary Outcomes
Outcome Description
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)
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)
Outcome Measure
Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs)
Outcome Time Frame
From first dose of study drug(s) to 28 days post-dose (up to approximately 1 year and 6 months)
Outcome Description
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
Outcome Measure
Number of Participants Experiencing Adverse Events (AEs)
Outcome Time Frame
From the first dose of study drug(s) to 30 days after the last dose; up to approximately 5 years and 10 months
Outcome Description
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.
Outcome Measure
Objective Response Rate (ORR)
Outcome Time Frame
Up to approximately 5 years and 10 months
Secondary Ids
Secondary Id
2017-001553-14
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
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)
Outcome Measure
Maximum Observed Plasma Concentration (Cmax) of Pamiparib
Outcome Time Frame
Cycle 1 Day 15 predose
Outcome Measure
Plasma Trough Concentrations of Pamiparib (Ctrough)
Outcome Time Frame
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.
Outcome Measure
Time to Reach Cmax (Tmax) of Pamiparib
Outcome Time Frame
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.
Outcome Measure
Area Under the Curve From Time 0 to 4 Hours (AUC0-4h) of Pamiparib
Outcome Time Frame
2 days before Cycle 1 Day 1 (Day -2) at predose, 30 min, 1, 2, 4, 6, 24, and 48 hours after dosing
Outcome Measure
Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Pamiparib
Outcome Time Frame
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)
Outcome Measure
Terminal Elimination Half-life (t1/2) of Pamiparib
Outcome Time Frame
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)
Outcome Measure
Apparent Clearance (CL/F) of Pamiparib
Outcome Time Frame
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)
Outcome Measure
Apparent Volume of Distribution During Terminal Phase (Vz/F) of Pamiparib
Outcome Time Frame
Predose (within 30 min prior to dose) and 1 hour post dose on Cycle 1 Day 1 and Cycle 1 Day 7
Outcome Measure
Plasma Concentration of Temozolomide (TMZ)
Outcome Description
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.
Outcome Time Frame
Up to approximately 5 years and 10 months
Outcome Measure
Disease Control Rate (DCR)
Outcome Description
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.
Outcome Time Frame
Up to approximately 5 years and 10 months
Outcome Measure
Duration of Response (DOR)
Outcome Description
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
Outcome Time Frame
Up to approximately 5 years and 10 months)
Outcome Measure
Progression Free Survival (PFS)
Outcome Description
OS is defined as the time from the date of the first dose of combination treatment to death due to any cause.
Outcome Time Frame
Up to approximately 5 years and 10 months
Outcome Measure
Overall Survival (OS)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Balazs Halmos
Investigator Email
bahalmos@montefiore.org
Investigator Phone