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

Study Overview
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Brief Summary
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The primary objective of this study is 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.

Official Title
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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

Conditions
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Locally Advanced or Metastatic Solid Tumors

Intervention / Treatment
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* Drug: Pamiparib
* Drug: Temozolomide


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Age ≥18 years old with advanced or metastatic stage solid tumors Eastern Cooperative Oncology Group (ECOG) status ≤ 1 and measurable disease per RECIST V1.1 (except for participants in dose escalation and prostate cancer participants) Additional inclusion criteria for dose expansion cohorts: Participants with homologous recombination deficiency (HRD+) or known BRCA mutant Ovarian cancer a. Previously received at least 1 line of platinum containing chemotherapy and No progression or recurrent disease in 6 months from last platinum containing regimen. Participants with HRD+ or known breast cancer susceptibility gene (BRCA) mutant Triple-Negative Breast Cancer a. 0 - 1 prior platinum-containing regimen (any treatment setting) and received ≤ 3 prior regimens (advanced or metastatic setting). Participants with HRD+ or known BRCA mutant Prostate cancer Chemotherapy-naïve or previously received ≤2 taxane-based regimens. May have pre-or post-treatment with a novel androgen receptor targeted agent. Participants Small cell lung and gastric cancer a. Previously received ≤ 2 prior lines of therapy. Participants with HRD+ NSCLC, head and neck cancer, esophageal cancer and soft tissue sarcomas Must have tumors with with HRD+ as centrally determined Must have received at least 1 but not more than 3 prior lines of therapy. Treatment naïve patients with soft tissue sarcoma might be allowed if standard of care therapy is not suitable or available. Key Exclusion Criteria: All participants Prior exposure to a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor. Refractory to platinum-based therapy. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (Dose Escalation) TMZ Pulse Dosing<br>Participants receive continuous BGB-290 and escalating flat doses of 40mg, 80mg, 100mg, 120mg (as 20 mg capsules) daily administered orally up to the maximum tolerated dose (MTD) of TMZ on Days 1 - 7 of a 28-day cycle. | Drug: Pamiparib<br>* 60 mg (20 mg capsules) administered orally twice a day<br>* Other names: BGB-290;Drug: Temozolomide<br>* Doses of up to 120 mg (as 20 mg capsules) administered orally once daily (QD) as specified in the treatment arm<br>* Other names: temodar;|
| Experimental: Arm B (Dose Escalation) TMZ Continuous Dosing<br>Participants receive continuous BGB-290 and escalating flat doses of 40mg, 80mg, 100mg, 120mg (as 20 mg capsules) daily administered orally up to the maximum tolerated dose (MTD) of TMZ on Days 1 - 28 of a 28-day cycle. | Drug: Pamiparib<br>* 60 mg (20 mg capsules) administered orally twice a day<br>* Other names: BGB-290;Drug: Temozolomide<br>* Doses of up to 120 mg (as 20 mg capsules) administered orally once daily (QD) as specified in the treatment arm<br>* Other names: temodar;|
| Experimental: Dose Expansion, 6 cohorts<br>Participants receive continuous BGB-290 and TMZ at the recommended phase 2 dose (RP2D) and schedule in 28 day cycles | Drug: Pamiparib<br>* 60 mg (20 mg capsules) administered orally twice a day<br>* Other names: BGB-290;Drug: Temozolomide<br>* Doses of up to 120 mg (as 20 mg capsules) administered orally once daily (QD) as specified in the treatment arm<br>* Other names: temodar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and nature of dose limiting toxicities (DLTs) as assessed by CTCAE. |  | From first dose BGB-290 and TMZ to 28 days post-dosing | 
| Number of participants experiencing Adverse Events (AEs) |  | From first dose BGB-290 and TMZ to 30 days post-dosing | 
| Number of participants experiencing Severe Adverse Events (SAEs) |  | From first dose BGB-290 and TMZ to 30 days post-dosing | 
| Objective Response Rate (ORR) |  | From first dose BGB-290 and TMZ to first documentation of disease progression, assessed up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum observed plasma concentration (Cmax) of BGB-290 and TMZ. |  | From first dose BGB-290 and TMZ to 30 days post-dosing | 
| lowest concentration reached before the next dose administered (Ctrough) of BGB-290 and TMZ. |  | From first dose BGB-290 and TMZ to 30 days post-dosing | 
| time to reach maximum (peak) plasma concentration (Tmax) of BGB-290 and TMZ. |  | From first dose BGB-290 and TMZ to 30 days post-dosing | 
| Duration of response (DOR). |  | From first dose BGB-290 and TMZ to first documentation of disease progression, assessed up to 5 years | 
| Disease control rate (DCR) |  | From first dose BGB-290 and TMZ to first documentation of disease progression while participant is alive, assessed to up 5 years | 
| Progression free survival (PFS) |  | From first dose BGB-290 and TMZ to first documentation of disease progression or death, whichever is first, assessed up to 5 years | 
| Overall survival (OS) |  | From first dose BGB-290 and TMZ until date of death, assessed up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovarian cancer, Triple negative breast cancer, Small cell lung cancer, Prostate 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