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

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

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.

Study Overview

• Status: Completed
• Conditions: Locally Advanced or Metastatic Solid Tumors
• Intervention / Treatment: Drug: Pamiparib; Drug: Temozolomide

• Study Type: Interventional
• Enrollment (Actual): 139
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris OBrien LifeHouse
    • Darlinghurst, New South Wales, Australia, 2010
      • Saint Vincents Hospital Sydney
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Icon Cancer Centre South Brisbane
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall dHebron
  • Barcelona, Spain, 08907
    • Ico H Duran I Reynals
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28050
    • Centro Integral Oncologico Clara Campal
  • Madrid, Spain, 28040
    • Start Madrid Fundacion Jimenez Diaz
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen de la Macarena
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • High Heaton, United Kingdom, NE7 7DN
    • Northern Centre for Cancer Care
  • London, United Kingdom, NW1 2PG
    • University College Hospital
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute UK
• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • START Midwest
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University in St Louis
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Park At Eastchester Einstein Campus
    • New York, New York, United States, 10029
      • Mount Sinai PRIME
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Cancer Center
  • Texas
    • Dallas, Texas, United States, 75230
      • Texas Oncology (Loop) Usor
    • Houston, Texas, United States, 77030-4009
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Pamiparib; Administered by mouth as a capsule twice daily; Other Names: BGB-290; Drug: Temozolomide; TMZ at various doses administered by mouth as a capsule once daily.; Other Names: TMZ; temodar
Experimental: 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	Drug: Pamiparib; Administered by mouth as a capsule twice daily; Other Names: BGB-290; Drug: Temozolomide; TMZ at various doses administered by mouth as a capsule once daily.; Other Names: TMZ; temodar
Experimental: 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	Drug: Pamiparib; Administered by mouth as a capsule twice daily; Other Names: BGB-290; Drug: Temozolomide; TMZ at various doses administered by mouth as a capsule once daily.; Other Names: TMZ; temodar
Experimental: 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	Drug: Pamiparib; Administered by mouth as a capsule twice daily; Other Names: BGB-290; Drug: Temozolomide; TMZ at various doses administered by mouth as a capsule once daily.; Other Names: TMZ; temodar
Experimental: 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	Drug: Pamiparib; Administered by mouth as a capsule twice daily; Other Names: BGB-290; Drug: Temozolomide; TMZ at various doses administered by mouth as a capsule once daily.; Other Names: TMZ; temodar
Experimental: 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	Drug: Pamiparib; Administered by mouth as a capsule twice daily; Other Names: BGB-290; Drug: Temozolomide; TMZ at various doses administered by mouth as a capsule once daily.; Other Names: TMZ; temodar
Experimental: 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	Drug: Pamiparib; Administered by mouth as a capsule twice daily; Other Names: BGB-290; Drug: Temozolomide; TMZ at various doses administered by mouth as a capsule once daily.; Other Names: TMZ; temodar
Experimental: 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	Drug: Pamiparib; Administered by mouth as a capsule twice daily; Other Names: BGB-290; Drug: Temozolomide; TMZ at various doses administered by mouth as a capsule once daily.; Other Names: TMZ; temodar
Experimental: 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	Drug: Pamiparib; Administered by mouth as a capsule twice daily; Other Names: BGB-290; Drug: Temozolomide; TMZ at various doses administered by mouth as a capsule once daily.; Other Names: TMZ; temodar
Experimental: 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	Drug: Pamiparib; Administered by mouth as a capsule twice daily; Other Names: BGB-290; Drug: Temozolomide; TMZ at various doses administered by mouth as a capsule once daily.; Other Names: TMZ; temodar
Experimental: 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	Drug: Pamiparib; Administered by mouth as a capsule twice daily; Other Names: BGB-290; Drug: Temozolomide; TMZ at various doses administered by mouth as a capsule once daily.; Other Names: TMZ; temodar
Experimental: 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	Drug: Pamiparib; Administered by mouth as a capsule twice daily; Other Names: BGB-290; Drug: Temozolomide; TMZ at various doses administered by mouth as a capsule once daily.; Other Names: TMZ; temodar
Experimental: 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	Drug: Pamiparib; Administered by mouth as a capsule twice daily; Other Names: BGB-290; Drug: Temozolomide; TMZ at various doses administered by mouth as a capsule once daily.; Other Names: TMZ; temodar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs)	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)	From first dose of study drug(s) to 28 days post-dose (up to approximately 1 year and 6 months)
Number of Participants Experiencing Adverse Events (AEs)	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	From the first dose of study drug(s) to 30 days after the last dose; up to approximately 5 years and 10 months
Objective Response Rate (ORR)	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.	Up to approximately 5 years and 10 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Pamiparib	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.	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)	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.	Up to approximately 5 years and 10 months
Duration of Response (DOR)	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.	Up to approximately 5 years and 10 months
Progression Free Survival (PFS)	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	Up to approximately 5 years and 10 months)
Overall Survival (OS)	OS is defined as the time from the date of the first dose of combination treatment to death due to any cause.	Up to approximately 5 years and 10 months

Collaborators and Investigators

• Sponsor: BeiGene
• Collaborators: Myriad Genetics, Inc.
• Investigators: Study Director: Study Director, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2017
• Primary Completion (Actual): May 4, 2023
• Study Completion (Actual): May 4, 2023

Study Registration Dates

• First Submitted: May 8, 2017
• First Submitted That Met QC Criteria: May 10, 2017
• First Posted (Actual): May 12, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Gastric cancer; Ovarian cancer; Head and neck cancer; Non small cell lung cancer; Small cell lung cancer; Soft tissue sarcoma; Esophageal cancer; temozolomide; Triple negative breast cancer; antineoplastic agents; BGB-290; alkylating, alkylating agents,; Poly (ADP-ribose) polymerase inhibitors; enzyme inhibitors; pamiparib
• Additional Relevant MeSH Terms: Neoplasms; Poly(ADP-ribose) Polymerase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide; Pamiparib
• Other Study ID Numbers: BGB-290-103; 2017-001553-14 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No