Study of Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 in Participants With Advanced or Refractory Tumors

NCT04249843 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: BGB-3245-AU-001
• Study Type: interventional
• Target: 109
• Locations: 2 countries
• Sites: 9

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and antitumor activity of BGB-3245 in participants with advanced or refractory solid tumors

Conditions

Solid Tumor; B-Raf Mutation-Related Tumors

Keywords

BGB3245; BRAF inhibitor; BRAF; KRAS; NRAS; Mitogen Activated Protein Kinase (MAPK) Pathway; BRAF fusion; BRAF Class II

Outcome Measures

Primary Outcomes (7)

• Phase 1a: Number of Participants and Severity Experiencing Adverse Events (AEs)

  Up to 30 days after the last dose of study drug

• Phase 1a: Number of Participants and Severity Experiencing Serious Adverse Events (SAEs)

  Up to 30 days after the last dose of study drug

• Phase 1a: number of Participants Experiencing AEs meeting protocol defined Dose-Limiting Toxicity (DLT) criteria

  From Cycle 1 Day to the end of Cycle 1 (Cycle 1 is 30 days)

• Phase 1a: Maximum Tolerated Dose (MTD) of BGB-3245, and the recommended Phase 2 Dose (RP2D) for BGB-3245

  The MTD is defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 33%.

  From Cycle 1 Day to the end of Cycle 1 (Cycle 1 is 30 days)

• Phase 1b: Recommended Phase 2 dose (RP2D) of BGB-3245

  The highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 33%

  From Cycle 1 Day to the end of Cycle 1 (Cycle 1 is 30 days)

• Phase 1b: Objective Response Rate (ORR) as assessed by the investigator

  ORR is defined as the percentage of participants with partial or complete response, as assessed by the investigator

  Up to 24 months

• Phase 1b: Further review of the ORR

  ORR is defined as the percentage of participants with partial or complete response in up to 15 participants with tumors harboring BRAF fusion mutations

  Up to 24 months

Secondary Outcomes (27)

• Phase 1a: Overall Response Rate (ORR) as Assessed by the Investigator

  Up to 24 months

• Phase 1a: Duration of Response (DOR) as Assessed by the Investigator

  Up to 24 months

• Phase 1a: Clinical Benefit Rate (CBR) as Assessed by the Investigator

  Up to 24 months

• Phase 1a: Best Overall Response (BOR) as Assessed by the Investigator

  Up to 24 months

• Phase 1a: Duration of Stable Disease (DSD)

  Up to 24 months

Study Arms (2)

Phase 1a: Dose Escalation

EXPERIMENTAL

BGB-3245 administered orally (PO)

Drug: BGB-3245

Phase 1b, Group 1: Dose Expansion

EXPERIMENTAL

BGB-3245 administered orally (PO)

Drug: BGB-3245

Interventions

BGB-3245 DRUG

administered orally (PO)

Also known as: Brimarafenib

Phase 1a: Dose Escalation; Phase 1b, Group 1: Dose Expansion

Eligibility Criteria

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

You may qualify if:

• Participants with histologically confirmed advanced or metastatic solid tumor who had disease progression during or after systemic anticancer therapies that previously demonstrated clinical benefit (eg, improved survival) in a representative population, or are unable to receive standard therapy(ies). In addition, participants must meet the following eligibility criteria for the corresponding phase of the study:
• Phase 1a: participants with a known mutation status and tumor harboring an oncogenic mutation of the v-RAF murine sarcoma viral oncogene homolog B (BRAF) gene (the mutations of primary interest are the BRAF Class II mutation, Class III mutation or BRAF fusion). In addition, participants with tumors harboring the mutation of the neuroblastoma RAS viral oncogene homolog (NRAS) gene or the Kirsten rat sarcoma virus oncogene homolog (KRAS) are eligible for Part 1a. For participants with KRAS mutations, tumor types of colorectal cancer (CRC) and pancreatic cancer are excluded.
• Phase 1b: participants must have a known mutation status and meet one of the following criteria according to the group they are enrolled into:
• I. Group 1: participants with tumor types other than CRC that harbor BRAF V600 mutations who have been treated and progressed on prior BRAF and/or mitogen activated protein kinase (MEK) inhibition.
• II. Group 2: participants with advanced solid tumors harboring a BRAF Class II mutation or a BRAF fusion mutation.
• III. Group 2 BRAF Fusion Expansion: Participants with advanced solid tumors harboring a BRAF fusion mutation
• Participants must provide archival tumor tissue or agree to a fresh tumor biopsy for mutation and biomarkers analysis (fresh tumor biopsies are strongly recommended)
• Participants must have radiologically measurable disease as defined by RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
• Adequate organ function and no transfusions within 14 days of first dose

You may not qualify if:

• Participants receiving cancer therapy (chemotherapy or other systemic anticancer therapies, immunotherapy, radiation therapy, or surgery) at the time of Cycle 1 Day 1.
• All participants who have received prior systemic anticancer treatment within the following time frames will be excluded:
• Systemic chemotherapy within 4 weeks or 6 weeks for nitrosourea, mitomycin prior to Cycle 1 Day 1; and
• Biologic therapy (i.e., antibodies), continuous or intermittent small-molecule therapies, or any other investigational agents within a period of 5 times the half-life of the agent or ≤4 weeks (whichever is shorter) prior to Cycle 1 Day 1.
• Severe or uncontrolled systemic disease.
• Clinically significant cardiac disease within 6 months of signing the ICF
• CNS metastases, leptomeningeal carcinomatosis or untreated spinal cord compression.
• Any unstable, preexisting major medical condition, including known human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• Systemic anti-cancer therapy within 2 weeks or 5 half-lives before first dose.
• Major surgical procedure or significant traumatic injury within 4 weeks prior to the first dose or anticipates need for major surgery while on study.

Sponsors & Collaborators

• MapKure, LLC: lead

Study Sites (9)

Cedars Sinai Medical Center

Beverly Hills, California, 90212, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

University of Virginia Comprehensive Cancer Centre

Charlottesville, Virginia, 22903, United States

Location

Blacktown Hospital

Blacktown, New South Wales, 2148, Australia

Location

The Kinghorn Cancer Centre, St Vincent Hospital Sydney

Sydney, New South Wales, 2010, Australia

Location

One Clinical Research

Nedlands, Perth, 6009, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 2010, Australia

Location

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: January 21, 2020
• First Posted: January 31, 2020
• Study Start: February 17, 2020
• Primary Completion: August 4, 2025
• Study Completion: August 4, 2025
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

AU (4); US (5)