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

A First-in-Human, Phase 1a/1b, Open Label, Dose-Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics, and Antitumor Activity of the RAF Dimer Inhibitor BGB-3245 in Patients With Advanced or Refractory Tumors

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

Study Overview

• Status: Terminated
• Conditions: Solid Tumor; B-Raf Mutation-Related Tumors
• Intervention / Treatment: Drug: BGB-3245

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Blacktown Hospital
    • Sydney, New South Wales, Australia, 2010
      • The Kinghorn Cancer Centre, St Vincent Hospital Sydney
  • Perth
    • Nedlands, Perth, Australia, 6009
      • One Clinical Research
  • Victoria
    • Melbourne, Victoria, Australia, 2010
      • Peter MacCallum Cancer Centre
• United States
  • California
    • Beverly Hills, California, United States, 90212
      • Cedars Sinai Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Comprehensive Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. 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:

   1. 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.
   2. 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

2. Participants must provide archival tumor tissue or agree to a fresh tumor biopsy for mutation and biomarkers analysis (fresh tumor biopsies are strongly recommended)
3. Participants must have radiologically measurable disease as defined by RECIST v1.1
4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
5. Adequate organ function and no transfusions within 14 days of first dose

Key Exclusion Criteria :

1. Participants receiving cancer therapy (chemotherapy or other systemic anticancer therapies, immunotherapy, radiation therapy, or surgery) at the time of Cycle 1 Day 1.

2. All participants who have received prior systemic anticancer treatment within the following time frames will be excluded:

   1. Systemic chemotherapy within 4 weeks or 6 weeks for nitrosourea, mitomycin prior to Cycle 1 Day 1; and
   2. 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.
3. Severe or uncontrolled systemic disease.
4. Clinically significant cardiac disease within 6 months of signing the ICF
5. CNS metastases, leptomeningeal carcinomatosis or untreated spinal cord compression.
6. Any unstable, preexisting major medical condition, including known human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
7. Systemic anti-cancer therapy within 2 weeks or 5 half-lives before first dose.
8. Major surgical procedure or significant traumatic injury within 4 weeks prior to the first dose or anticipates need for major surgery while on study.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1a: Dose Escalation; BGB-3245 administered orally (PO)	Drug: BGB-3245; administered orally (PO); Other Names: Brimarafenib
Experimental: Phase 1b, Group 1: Dose Expansion; BGB-3245 administered orally (PO)	Drug: BGB-3245; administered orally (PO); Other Names: Brimarafenib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
Phase 1a: Progression Free Survival (PFS)	Up to 24 months
Phase 1a: Plasma Concentration of BGB-3245	Within 60 minutes predose up to 72 hours postdose
Phase 1a: Maximum Observed Plasma Concentration (Cmax) of BGB-3245	Within 60 minutes predose up to 72 hours postdose
Phase 1a: Time to Maximum Plasma Concentration (Tmax) of BGB-3245	60 minutes predose up to 72 hours postdose
Phase 1a: Time Taken for Half the Initial Dose Administered To Be Eliminated From The Body (T1/2) of BGB-3245	60 minutes predose up to 72 hours postdose
Phase 1a: Area Under the Concentration-Time Curve of 0-infinity Days (AUC0-inf) of BGB-3245	60 minutes predose up to 72 hours postdose
Phase 1a:Area Under the Concentration-Time Curve of 0-Last hour (AUC0-last) of BGB-3245	60 minutes predose up to 72 hours postdose
Phase 1a: Drug Clearance (CL/F) of BGB-3245	60 minutes predose up to 72 hours postdose
Phase 1a: Apparent Volume of Distribution (Vz/F) of BGB-3245	60 minutes predose up to 72 hours postdose
Phase 1a: Steady State Area Under the Concentration-Time Curve of 0- Last hour (AUCLast, ss) of BGB-3245	60 minutes predose up to 72 hours postdose
Phase 1a: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of BGB-3245	60 minutes predose up to 72 hours postdose
Phase 1a: Steady State Time to Maximum Plasma Concentration (Tmax, ss) of BGB-3245	60 minutes predose up to 72 hours postdose
Phase 1b: Progression-free survival (PFS) as Assessed by the Investigator	Up to 36 months
Phase 1b: Duration of Response (DOR) as Assessed by the Investigator	Up to 24 months
Phase 1b: Disease-Control Rate (DCR) as Assessed by the Investigator	Up to 24 months
Phase 1b: Duration of Stable Disease (DSD) as Assessed by the Investigator	Up to 24 months
Phase 1b: Clinical Benefit Rate (CBR) as Assessed by the Investigator	Up to 24 months
Phase 1b: Overall Survival	Up to 36 months
Phase 1b: Number of Participants Experiencing Adverse Events (AEs)	Up to 30 days after the last dose of study drug
Phase 1b: Number of Participants Experiencing Serious Adverse Events (SAEs)	Up to 30 days after the last dose of study drug
Phase 1b: Plasma Concentration of BGB-3245	60 minutes predose up to 3 hours postdose
Phase 1b: Steady State Trough Observed Plasma Concentration (Ctrough, SS) of BGB-3245	60 minutes predose up to 72 hours postdose

Collaborators and Investigators

• Sponsor: MapKure, LLC

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2020
• Primary Completion (Actual): August 4, 2025
• Study Completion (Actual): August 4, 2025

Study Registration Dates

• First Submitted: January 21, 2020
• First Submitted That Met QC Criteria: January 29, 2020
• First Posted (Actual): January 31, 2020

Study Record Updates

• Last Update Posted (Estimated): September 11, 2025
• Last Update Submitted That Met QC Criteria: September 4, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: BRAF fusion; BRAF inhibitor; KRAS; BRAF; NRAS; BRAF Class II; BGB3245; Mitogen Activated Protein Kinase (MAPK) Pathway
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: BGB-3245-AU-001

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
• product manufactured in and exported from the U.S.: No