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

NCT03150810 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: BGB-290-1032017-001553-14
• Study Type: interventional
• Target: 139
• Locations: 4 countries
• Sites: 22

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.

Conditions

Locally Advanced or Metastatic Solid Tumors

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (13)

• Maximum Observed Plasma Concentration (Cmax) 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 (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

Study Arms (13)

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

EXPERIMENTAL

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; Drug: Temozolomide

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

EXPERIMENTAL

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; Drug: Temozolomide

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

EXPERIMENTAL

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; Drug: Temozolomide

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

EXPERIMENTAL

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; Drug: Temozolomide

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

EXPERIMENTAL

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; Drug: Temozolomide

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

EXPERIMENTAL

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; Drug: Temozolomide

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

EXPERIMENTAL

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; Drug: Temozolomide

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

EXPERIMENTAL

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; Drug: Temozolomide

Dose Expansion: Gastric Cancer

EXPERIMENTAL

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; Drug: Temozolomide

Dose Expansion: Ovarian Cancer

EXPERIMENTAL

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; Drug: Temozolomide

Dose Expansion: SCLC

EXPERIMENTAL

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; Drug: Temozolomide

Dose Expansion: TNBC

EXPERIMENTAL

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; Drug: Temozolomide

Dose Expansion: Other HRD+ Cancers

EXPERIMENTAL

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; Drug: Temozolomide

Interventions

Pamiparib DRUG

Administered by mouth as a capsule twice daily

Also known as: BGB-290

Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7); Dose Escalation: Pamiparib + TMZ 120 mg (Days 1-7); Dose Escalation: Pamiparib + TMZ 20 mg (Days 1-28); Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-14); Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-28); Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7); Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7); Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 milligrams (mg) (Days 1-7); Dose Expansion: Gastric Cancer; Dose Expansion: Other HRD+ Cancers; Dose Expansion: Ovarian Cancer; Dose Expansion: SCLC; Dose Expansion: TNBC

Temozolomide DRUG

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

Also known as: TMZ, temodar

Dose Escalation: Pamiparib + TMZ 100 mg (Days 1-7); Dose Escalation: Pamiparib + TMZ 120 mg (Days 1-7); Dose Escalation: Pamiparib + TMZ 20 mg (Days 1-28); Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-14); Dose Escalation: Pamiparib + TMZ 40 mg (Days 1-28); Dose Escalation: Pamiparib + TMZ 60 mg (Days 1-7); Dose Escalation: Pamiparib + TMZ 80 mg (Days 1-7); Dose Escalation: Pamiparib + Temozolomide (TMZ) 40 milligrams (mg) (Days 1-7); Dose Expansion: Gastric Cancer; Dose Expansion: Other HRD+ Cancers; Dose Expansion: Ovarian Cancer; Dose Expansion: SCLC; Dose Expansion: TNBC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• Prior treatment with a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor.
• Refractory to platinum-based therapy (dose-expansion cohort).

Sponsors & Collaborators

• BeiGene: lead
• Myriad Genetics, Inc.: collaborator

Study Sites (22)

Start Midwest

Grand Rapids, Michigan, 49503, United States

Location

Washington University in St Louis

St Louis, Missouri, 63110, United States

Location

Mount Sinai Prime

New York, New York, 10029, United States

Location

Montefiore Medical Park At Eastchester Einstein Campus

The Bronx, New York, 10467, United States

Location

Sarah Cannon Cancer Center

Nashville, Tennessee, 37203, United States

Location

Texas Oncology (Loop) Usor

Dallas, Texas, 75230, United States

Location

The University of Texas Md Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

Chris Obrien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Saint Vincents Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Icon Cancer Centre South Brisbane

South Brisbane, Queensland, 4101, Australia

Location

Peter Maccallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Hospital Universitario Vall Dhebron

Barcelona, 08035, Spain

Location

Ico H Duran I Reynals

Barcelona, 08907, Spain

Location

Hospital Universitario Ramon Y Cajal

Madrid, 28034, Spain

Location

Start Madrid Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Centro Integral Oncologico Clara Campal

Madrid, 28050, Spain

Location

Hospital Universitario Virgen de La Macarena

Seville, 41009, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Northern Centre For Cancer Care

High Heaton, NE7 7DN, United Kingdom

Location

University College Hospital

London, NW1 2PG, United Kingdom

Location

Sarah Cannon Research Institute Uk

London, W1G 6AD, United Kingdom

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Triple Negative Breast Neoplasms; Small Cell Lung Carcinoma; Stomach Neoplasms; Head and Neck Neoplasms; Esophageal Neoplasms; Sarcoma; Carcinoma, Non-Small-Cell Lung

Interventions

pamiparib; Temozolomide

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Esophageal Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

+1-877-828-5568

Study Officials

• Study Director

  BeiGene

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2017
• First Posted: May 12, 2017
• Study Start: June 28, 2017
• Primary Completion: May 4, 2023
• Study Completion: May 4, 2023
• Last Updated: December 20, 2024
• Results First Posted: December 20, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share

Locations

US (7); AU (4); GB (4); ES (7)