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

BeiGene

Status and phase: Completed; Phase 1

Conditions: Locally Advanced or Metastatic Solid Tumors

Treatments: Drug: Pamiparib; Drug: Temozolomide

Study type: Interventional

Funder types: Industry

Identifiers

NCT03150810

BGB-290-103

2017-001553-14 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 139 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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139 participants in 13 patient groups

Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 milligrams (mg) (Days 1-7)

Experimental group

Description:

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

Treatment:

Drug: Temozolomide

Drug: Pamiparib

Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7)

Experimental group

Description:

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

Treatment:

Drug: Temozolomide

Drug: Pamiparib

Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7)

Experimental group

Description:

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

Treatment:

Drug: Temozolomide

Drug: Pamiparib

Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7)

Experimental group

Description:

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

Treatment:

Drug: Temozolomide

Drug: Pamiparib

Dose Escalation: Pamiparib + TMZ 120 mg (Days 1-7)

Experimental group

Description:

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

Treatment:

Drug: Temozolomide

Drug: Pamiparib

Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-14)

Experimental group

Description:

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

Treatment:

Drug: Temozolomide

Drug: Pamiparib

Dose Escalation: Pamiparib + TMZ 20 mg (Days 1-28)

Experimental group

Description:

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

Treatment:

Drug: Temozolomide

Drug: Pamiparib

Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-28)

Experimental group

Description:

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

Treatment:

Drug: Temozolomide

Drug: Pamiparib

Dose Expansion: Gastric Cancer

Experimental group

Description:

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

Treatment:

Drug: Temozolomide

Drug: Pamiparib

Dose Expansion: Ovarian Cancer

Experimental group

Description:

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

Treatment:

Drug: Temozolomide

Drug: Pamiparib

Dose Expansion: SCLC

Experimental group

Description:

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

Treatment:

Drug: Temozolomide

Drug: Pamiparib

Dose Expansion: TNBC

Experimental group

Description:

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

Treatment:

Drug: Temozolomide

Drug: Pamiparib

Dose Expansion: Other HRD+ Cancers

Experimental group

Description:

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

Treatment:

Drug: Temozolomide

Drug: Pamiparib