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Completed

NCT Number: NCT03150810

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

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.

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Key information

Conditions

Locally Advanced or Metastatic Solid Tumors Adnexal Diseases Breast Diseases Breast Neoplasms Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Esophageal Diseases Esophageal Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gastrointestinal Diseases Gastrointestinal Neoplasms Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Head and Neck Neoplasms Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Connective and Soft Tissue Ovarian Diseases Ovarian Neoplasms Respiratory Tract Diseases Respiratory Tract Neoplasms Sarcoma Skin Diseases Skin and Connective Tissue Diseases Small Cell Lung Carcinoma Stomach Diseases Stomach Neoplasms Thoracic Neoplasms Triple Negative Breast Neoplasms Urogenital Diseases Urogenital Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Chris Obrien Lifehouse, Camperdown, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • 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 Exclusion Criteria: 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.

Treatment and study plan

Pamiparib

Drug

Administered by mouth as a capsule twice daily

Other names: BGB-290

Temozolomide

Drug

TMZ at various doses administered by mouth as a capsule once daily.

Other names: TMZ, temodar

Primary outcomes

  1. Dose Escalation: Number of Participants With Dose Limiting Toxicities (DLTs)

    Time frame: 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)

  2. Number of Participants Experiencing Adverse Events (AEs)

    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

    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

  3. Objective Response Rate (ORR)

    Time frame: 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 outcomes

  1. Maximum Observed Plasma Concentration (Cmax) of Pamiparib

    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)

    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. Plasma Trough Concentrations of Pamiparib (Ctrough)

    Time frame: Cycle 1 Day 15 predose

  3. Time to Reach Cmax (Tmax) of Pamiparib

    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.

  4. Area Under the Curve From Time 0 to 4 Hours (AUC0-4h) of Pamiparib

    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.

  5. Area Under the Curve From Time 0 to Infinity (AUC0-inf) of Pamiparib

    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

  6. Terminal Elimination Half-life (t1/2) of Pamiparib

    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)

  7. Apparent Clearance (CL/F) of Pamiparib

    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)

  8. Apparent Volume of Distribution During Terminal Phase (Vz/F) of Pamiparib

    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)

  9. Plasma Concentration of Temozolomide (TMZ)

    Time frame: Predose (within 30 min prior to dose) and 1 hour post dose on Cycle 1 Day 1 and Cycle 1 Day 7

  10. Disease Control Rate (DCR)

    Time frame: 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.

  11. Duration of Response (DOR)

    Time frame: 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.

  12. Progression Free Survival (PFS)

    Time frame: 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

  13. Overall Survival (OS)

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

BeiGene

Industry

Collaborators

  • Myriad Genetics, Inc.

Registry information

Official study 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

Important dates

Study start
2017
Primary completion
2023
Study completion
2023
First posted
May 12, 2017
Registry last updated
Dec 20, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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