Solid TumorPhase 1NCT04249843

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

A Phase 1 study testing Brimarafenib in people with Solid Tumor and B-Raf Mutation-Related Tumors, run by MapKure, LLC at 9 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This Phase 1a/1b study evaluated the safety, pharmacokinetics, and preliminary antitumor activity of the investigational oral RAF dimer inhibitor BGB-3245 (brimarafenib) in participants with advanced or refractory solid tumors. Dose escalation evaluated safety/tolerability and informed dose selection. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Solid Tumor, B-Raf Mutation-Related Tumors
What is being tested?: Brimarafenib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 109 participants
Where: 9 sitesin 2 countries
Study dates: 10 Feb 2020to 8 Aug 2025
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Participants had histologically confirmed advanced or metastatic solid tumors and experienced disease progression during or after systemic anticancer therapies that previously demonstrated clinical benefit (improved survival) in a representative population, or were unable to receive standard therapy. In addition, participants had to meet the eligibility criteria for the corresponding phase of the study:
Phase 1a: Participants had a known mutation status and tumors harboring an oncogenic mutation of the BRAF gene. The mutations of primary interest were BRAF Class II mutations, Class III mutations, or BRAF fusions. In addition, participants with tumors harboring mutations of the neuroblastoma RAS viral oncogene homolog (NRAS) gene or the Kirsten rat sarcoma virus oncogene homolog (KRAS) gene were eligible for Phase 1a. For participants with KRAS mutations, tumor types of colorectal cancer (CRC) and pancreatic cancer were excluded.
Phase 1b: Participants had a known mutation status and met one of the following criteria according to the group in which they were enrolled:
Group 1: Participants with tumor types other than CRC that harbored BRAF V600 mutations and who had been treated and progressed on prior BRAF and/or mitogen-activated protein kinase (MEK) inhibition.
Group 2: Participants with advanced solid tumors harboring a BRAF Class II mutation or a BRAF fusion mutation.
Group 2 BRAF Fusion Expansion: Participants with advanced solid tumors harboring a BRAF fusion mutation.

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Participants provided archival tumor tissue or agreed to a fresh tumor biopsy for mutation and biomarker analysis. Fresh tumor biopsies were strongly recommended.
Participants had radiologically measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
Participants had an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
Participants demonstrated adequate organ function and had not received blood transfusions within 14 days prior to the first dose of study drug.

Who cannot join

Participants were receiving cancer therapy (chemotherapy or other systemic anticancer therapies, immunotherapy, radiation therapy, or surgery) at the time of Cycle 1 Day 1.
Participants who had received prior systemic anticancer treatment within the following time frames were excluded:
Systemic chemotherapy within 4 weeks, or 6 weeks for nitrosourea or mitomycin, prior to Cycle 1 Day 1.
Biologic therapy (e.g., monoclonal antibodies), continuous or intermittent small-molecule therapies, or any other investigational agents within a period of five times the half-life of the agent or ≤4 weeks (whichever was shorter) prior to Cycle 1 Day 1.
Participants with severe or uncontrolled systemic disease.
Participants with clinically significant cardiac disease within 6 months of signing the informed consent form (ICF).

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Participants with central nervous system (CNS) metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression.
Participants with any unstable, preexisting major medical condition, including known human immunodeficiency virus (HIV) infection, or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
Participants who received systemic anticancer therapy within 2 weeks or five half-lives before the first dose.
Participants who underwent a major surgical procedure or significant traumatic injury within 4 weeks prior to the first dose, or who anticipated the need for major surgery while on study.
Note: Additional protocol-defined inclusion or exclusion criteria may have applied.

Trial locations and contacts

9 sites in 2 countries.

Country

City, postcode or hospital

9 sites in 2 countries

United States5 sites

Cedars Sinai Medical Center
Beverly Hills, California, 90212
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of Virginia Comprehensive Cancer Centre
Charlottesville, Virginia, 22903
MD Anderson
Houston, Texas, 77030
Memorial Sloan Kettering Cancer Center
New York, New York, 10065

Other trials in United States

Australia4 sites

Blacktown Hospital
Blacktown, New South Wales, 2148
Peter MacCallum Cancer Centre
Melbourne, Victoria, 2010
One Clinical Research
Nedlands, Perth, 6009
The Kinghorn Cancer Centre, St Vincent Hospital Sydney
Sydney, New South Wales, 2010

Other trials in Australia

About this study

Official title: 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

Conditions: Solid Tumor, B-Raf Mutation-Related Tumors
Being tested: Brimarafenib
Keywords: BGB3245, BRAF inhibitor, BRAF, KRAS, NRAS, Mitogen Activated Protein Kinase (MAPK) Pathway, BRAF fusion, BRAF Class II

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BrimarafenibDrug
Also called BGB-3245
administered orally (PO) once daily at doses specified in the description of each arm

Study groups in NCT04249843
Study group	Role	What they receive
Phase 1a: Brimarafenib 5 mg	Experimental	Participants received brimarafenib 5 mg orally on Day 1 and then daily from Day 4 onwards. Participants continued treatment until disease progression, unacceptable toxicity, or study completion. Receives: Drug: Brimarafenib
Phase 1a: Brimarafenib 10 mg	Experimental	Participants received brimarafenib 10 mg orally on Day 1 and then daily from Day 4 onwards. Participants continued treatment until disease progression, unacceptable toxicity, or study completion. Receives: Drug: Brimarafenib
Phase 1a: Brimarafenib 15 mg	Experimental	Participants received brimarafenib 15 mg orally on Day 1 and then daily from Day 4 onwards. Participants continued treatment until disease progression, unacceptable toxicity, or study completion. Receives: Drug: Brimarafenib
Phase 1a: Brimarafenib 25 mg	Experimental	Participants received brimarafenib 25 mg orally on Day 1 and then daily from Day 4 onwards. Participants continued treatment until disease progression, unacceptable toxicity, or study completion. Receives: Drug: Brimarafenib
Phase 1a: Brimarafenib 40 mg	Experimental	Participants received brimarafenib 40 mg orally on Day 1 and then daily from Day 4 onwards. Participants continued treatment until disease progression, unacceptable toxicity, or study completion. Receives: Drug: Brimarafenib
Phase 1a: Brimarafenib 60 mg	Experimental	Participants received brimarafenib 60 mg orally on Day 1 and then daily from Day 4 onwards. Participants continued treatment until disease progression, unacceptable toxicity, or study completion. Receives: Drug: Brimarafenib
Phase 1b: Group 1 (Brimarafenib 25 mg)	Experimental	Participants with solid tumors harboring B-Raf Proto-Oncogene, Serine/Threonine Kinase (BRAF) V600 mutations (excluding colorectal cancer [CRC]) who had progressed on prior BRAF and/or MEK (mitogen-activated protein kinase) inhibition were randomized to receive 25 mg of brimarafenib once daily. Participants continued treatment until disease progression, unacceptable toxicity, or study completion. Receives: Drug: Brimarafenib
Phase 1b: Group 1 (Brimarafenib 40 mg Randomized)	Experimental	Participants with solid tumors harboring BRAF V600 mutations (excluding CRC) who had progressed on prior BRAF and/or MEK inhibition were randomized to receive 40 mg of brimarafenib once daily. Participants continued treatment until disease progression, unacceptable toxicity, or study completion. Receives: Drug: Brimarafenib
Phase 1b: Group 1 (Brimarafenib 40 mg Non-Randomized)	Experimental	Participants with solid tumors harboring BRAF V600 mutations (excluding CRC) enrolled under Protocol Version 4.0 were treated with 40 mg of brimarafenib once daily without randomization. Participants continued treatment until disease progression, unacceptable toxicity, or study completion. Receives: Drug: Brimarafenib
Phase 1b: Group 2 (Brimarafenib 40 mg)	Experimental	Participants with advanced solid tumors harboring BRAF Class II mutations or a BRAF fusion mutation were treated with 40 mg of brimarafenib once daily. Participants continued treatment until disease progression, unacceptable toxicity, or study completion. Receives: Drug: Brimarafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

Phase 1a: Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
SAEs were defined as adverse events that resulted in death, were life-threatening, required or prolonged hospitalization, caused significant disability, or were considered important medical events.
Measured: From first dose up to 30 days after the last dose of study treatment. Maximum treatment duration was 47 months.
Phase 1a: Maximum Tolerated Dose (MTD) of Brimarafenib
The MTD was determined by the Safety Monitoring Committee (SMC) based on the occurrence of dose-limiting toxicities (DLTs), overall safety, and tolerability. The MTD reflects the dose associated with an acceptable level of toxicity (30%).
Measured: From first dose through the end of Cycle 1 (approximately 30 days)
Phase 1b: Recommended Phase 2 Dose (RP2D) Confirmation
The optimal RP2D was to be determined based on safety, tolerability, efficacy, and pharmacokinetic (PK) data obtained from participants treated with the two dose levels tested in Phase 1b (25 mg and 40 mg). The RP2D could not be determined since the study was terminated early.
Measured: From first dose of study drug through last dose (maximum treatment duration in Phase 1b was 25 months)
Phase 1b: Objective Response Rate (ORR)
ORR was defined as the percentage of participants who achieved a best overall response of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Measured: From first dose until disease progression or death, Maximum treatment duration was 25 months.

Secondary outcomes (18)

Phase 1a: ORR
ORR was defined as the percentage of participants who achieved a best overall response of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Measured: From first dose until disease progression or death, Maximum treatment duration was 47 months.
Duration of Response (DOR)
DOR was defined as the time from the date that a confirmed response (CR or PR) was first observed per RECIST 1.1 to the date of first documented disease progression or death, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method.
Measured: From first dose until disease progression or death, Maximum treatment duration was 47 months in Phase 1a and 25 months in Phase 1b.
Clinical Benefit Rate (CBR)
CBR is defined as the percentage of participants with confirmed CR, PR, or durable stable disease (stable disease ≥ 24 weeks).
Measured: From first dose until disease progression or death, Maximum treatment duration was 47 months.
Progression-free Survival (PFS)
PFS was defined as the time from randomization to the date of first documented disease progression per RECIST v1.1 or death from any cause, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method.
Measured: From first dose until disease progression or death, Maximum treatment duration was 47 months Phase 1a and 25 months in Phase 1b.
Duration of Stable Disease (DSD)
DSD is defined as the time interval, in the absence of either confirmed CR or PR, between the date of the first administration of study drug and the first documented disease progression per RECIST v1.1 or death due to any cause, whichever occurred first.
Measured: From first dose until disease progression or death, Maximum treatment duration was 47 months Phase 1a and 25 months in Phase 1b.
Phase 1b: Disease Control Rate (DCR)
DCR is defined as the percentage of participants with a best overall response of CR, PR, or SD per RECIST v1.1 criteria. DCR reflects the percentage of participants whose disease did not progress during the study, including those with confirmed responses and those with durable SD.
Measured: From first dose until death, maximum treatment duration was 25 months.
Phase 1b: Overall Survival (OS)
OS was defined as the time from randomization to the date of death from any cause. Median OS was estimated using the Kaplan-Meier method.
Measured: From first dose until death, assessed maximum treatment duration was 25 months.
Phase 1a: Trough Plasma Concentration (Ctrough) of Brimarafenib
Ctrough is the observed concentration at predose.
Measured: Predose on Cycle 1 Day 15; Cycle 2 Day 1, Cycle 3 Day 1, and Cycle 4 Day 1. Each cycle was 28 days.
Phase 1a: Area Under the Concentration-time Curve From Dosing to Time of Last Quantifiable Concentration (AUClast) of Brimarafenib
Measured: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, and 8 hours postdose); Cycle 1 Days 2, 3, 4, 8, and 15; Cycle 2 Day 1 (predose and 1, 2, 3, 4, 6, and 8 hours postdose)
Phase 1a: Area Under the Concentration-time Curve From Dosing Time to Time Tau (Tau=24 Hours) of Brimarafenib
Measured: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, and 24 hours postdose)
Phase 1a: Area Under the Concentration-time Curve From Dosing Extrapolated to Infinity (AUC0-inf) of Brimarafenib
Measured: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours postdose)
Phase 1a: Maximum Observed Plasma Concentration (Cmax) of Brimarafenib
Measured: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours postdose); Cycle 2 Day 1 (predose and 1, 2, 3, 4, 6, and 8 hours postdose)
Phase 1a: Time to Maximum Observed Plasma Concentration (Tmax) of Brimarafenib
Measured: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, a 8, 24, 48, and 72 hours postdose); Cycle 2 Day 1 (predose and 1, 2, 3, 4, 6, and 8 hours postdose)
Phase 1a: Elimination Half-Life (t½) of Brimarafenib
Measured: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours postdose)
Phase 1a: Apparent Oral Clearance (CL/F) of Brimarafenib
Measured: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours postdose)
Phase 1a: Apparent Oral Volume of Distribution (Vz/F) of Brimarafenib
Measured: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours postdose)
Phase 1b: Plasma Concentrations for Brimarafenib
Measured: C1D1 (predose, 1, 3h postdose); C1D3, D8, D22 (±2d; predose, 2-4h postdose on D22); C2D1 (predose, 1, 3h); C3, 4, 6, 8, 10, 12 D1 and every 3rd cycle (predose); and at treatment discontinuation (2-4h).
Phase 1b: Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
SAEs were defined as events that resulted in death, were life-threatening, required or prolonged hospitalization, caused significant disability, or were considered important medical events.
Measured: From first dose until 30 days after last dose of study treatment. Maximum treatment duration was 25 months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

10 Feb 20208 Aug 2025

First posted31 Jan 2020
Study start10 Feb 2020
Primary completion8 Aug 2025
Study completion8 Aug 2025

Why it stopped: The study was terminated by the sponsor for reasons unrelated to safety.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Solid TumorStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 109 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04249843
Sponsor's protocol ID: BGB-3245-AU-001
Status last verified: Apr 2026
First submitted: 21 Jan 2020
Last updated: 31 Aug 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes

Publications

Alison M. Schram, Vivek Subbiah, Ryan Sullivan, Rasha Cosman, Jia Liu, Eric I. Sbar, Thuy Hoang, Jiarong Chen, Mark Johnson, Vincent Amoruccio, Todd Shearer, Adeela Kamal, Jocelyn Lewis, Wenlin Shao, Badreddin Edris, Lusong Luo, Jayesh Desai; Abstract CT031: 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. Cancer Res 15 April 2023; 83 (8_Supplement): CT031. https://doi.org/10.1158/1538-7445.AM2023-CT031

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Solid Tumor trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT04249843
Acronym / sponsor ID: BGB-3245-AU-001
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
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: The study was terminated by the sponsor for reasons unrelated to safety.
Enrolment: 109 participants (actual)
Lead sponsor: MapKure, LLCIndustry (pharma, biotech, devices)
Study start: 10 Feb 2020 (actual)
Primary completion: 8 Aug 2025 (actual)
Study completion: 8 Aug 2025 (actual)
First posted: 31 Jan 2020 (actual)
Results: Posted 31 Aug 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 10

Arm	Type	Receives
Phase 1a: Brimarafenib 5 mg	Experimental	Drug: BrimarafenibParticipants received brimarafenib 5 mg orally on Day 1 and then daily from Day 4 onwards. Participants continued treatment until disease progression, unacceptable toxicity, or study completion.
Phase 1a: Brimarafenib 10 mg	Experimental	Drug: BrimarafenibParticipants received brimarafenib 10 mg orally on Day 1 and then daily from Day 4 onwards. Participants continued treatment until disease progression, unacceptable toxicity, or study completion.
Phase 1a: Brimarafenib 15 mg	Experimental	Drug: BrimarafenibParticipants received brimarafenib 15 mg orally on Day 1 and then daily from Day 4 onwards. Participants continued treatment until disease progression, unacceptable toxicity, or study completion.
Phase 1a: Brimarafenib 25 mg	Experimental	Drug: BrimarafenibParticipants received brimarafenib 25 mg orally on Day 1 and then daily from Day 4 onwards. Participants continued treatment until disease progression, unacceptable toxicity, or study completion.
Phase 1a: Brimarafenib 40 mg	Experimental	Drug: BrimarafenibParticipants received brimarafenib 40 mg orally on Day 1 and then daily from Day 4 onwards. Participants continued treatment until disease progression, unacceptable toxicity, or study completion.
Phase 1a: Brimarafenib 60 mg	Experimental	Drug: BrimarafenibParticipants received brimarafenib 60 mg orally on Day 1 and then daily from Day 4 onwards. Participants continued treatment until disease progression, unacceptable toxicity, or study completion.
Phase 1b: Group 1 (Brimarafenib 25 mg)	Experimental	Drug: BrimarafenibParticipants with solid tumors harboring B-Raf Proto-Oncogene, Serine/Threonine Kinase (BRAF) V600 mutations (excluding colorectal cancer [CRC]) who had progressed on prior BRAF and/or MEK (mitogen-activated protein kinase) inhibition were randomized to receive 25 mg of brimarafenib once daily. Participants continued treatment until disease progression, unacceptable toxicity, or study completion.
Phase 1b: Group 1 (Brimarafenib 40 mg Randomized)	Experimental	Drug: BrimarafenibParticipants with solid tumors harboring BRAF V600 mutations (excluding CRC) who had progressed on prior BRAF and/or MEK inhibition were randomized to receive 40 mg of brimarafenib once daily. Participants continued treatment until disease progression, unacceptable toxicity, or study completion.
Phase 1b: Group 1 (Brimarafenib 40 mg Non-Randomized)	Experimental	Drug: BrimarafenibParticipants with solid tumors harboring BRAF V600 mutations (excluding CRC) enrolled under Protocol Version 4.0 were treated with 40 mg of brimarafenib once daily without randomization. Participants continued treatment until disease progression, unacceptable toxicity, or study completion.
Phase 1b: Group 2 (Brimarafenib 40 mg)	Experimental	Drug: BrimarafenibParticipants with advanced solid tumors harboring BRAF Class II mutations or a BRAF fusion mutation were treated with 40 mg of brimarafenib once daily. Participants continued treatment until disease progression, unacceptable toxicity, or study completion.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Participants had histologically confirmed advanced or metastatic solid tumors and experienced disease progression during or after systemic anticancer therapies that previously demonstrated clinical benefit (improved survival) in a representative population, or were unable to receive standard therapy. In addition, participants had to meet the eligibility criteria for the corresponding phase of the study:
Participants provided archival tumor tissue or agreed to a fresh tumor biopsy for mutation and biomarker analysis. Fresh tumor biopsies were strongly recommended.
Participants had radiologically measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
Participants had an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
Participants demonstrated adequate organ function and had not received blood transfusions within 14 days prior to the first dose of study drug.

Key exclusion criteria (11 listed)

Participants were receiving cancer therapy (chemotherapy or other systemic anticancer therapies, immunotherapy, radiation therapy, or surgery) at the time of Cycle 1 Day 1.
Participants who had received prior systemic anticancer treatment within the following time frames were excluded:
Participants with severe or uncontrolled systemic disease.
Participants with clinically significant cardiac disease within 6 months of signing the informed consent form (ICF).
Participants with central nervous system (CNS) metastases, leptomeningeal carcinomatosis, or untreated spinal cord compression.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BrimarafenibAlso: BGB-3245administered orally (PO) once daily at doses specified in the description of each arm	Drug	Phase 1a: Brimarafenib 10 mg, Phase 1a: Brimarafenib 15 mg, Phase 1a: Brimarafenib 25 mg, Phase 1a: Brimarafenib 40 mg, Phase 1a: Brimarafenib 5 mg, Phase 1a: Brimarafenib 60 mg, Phase 1b: Group 1 (Brimarafenib 25 mg), Phase 1b: Group 1 (Brimarafenib 40 mg Non-Randomized), Phase 1b: Group 1 (Brimarafenib 40 mg Randomized), Phase 1b: Group 2 (Brimarafenib 40 mg)

Primary outcome

Phase 1a: Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From first dose up to 30 days after the last dose of study treatment. Maximum treatment duration was 47 months.
SAEs were defined as adverse events that resulted in death, were life-threatening, required or prolonged hospitalization, caused significant disability, or were considered important medical events.
Phase 1a: Maximum Tolerated Dose (MTD) of Brimarafenib
Time frame: From first dose through the end of Cycle 1 (approximately 30 days)
The MTD was determined by the Safety Monitoring Committee (SMC) based on the occurrence of dose-limiting toxicities (DLTs), overall safety, and tolerability. The MTD reflects the dose associated with an acceptable level of toxicity (30%).
Phase 1b: Recommended Phase 2 Dose (RP2D) Confirmation
Time frame: From first dose of study drug through last dose (maximum treatment duration in Phase 1b was 25 months)
The optimal RP2D was to be determined based on safety, tolerability, efficacy, and pharmacokinetic (PK) data obtained from participants treated with the two dose levels tested in Phase 1b (25 mg and 40 mg). The RP2D could not be determined since the study was terminated early.
Phase 1b: Objective Response Rate (ORR)
Time frame: From first dose until disease progression or death, Maximum treatment duration was 25 months.
ORR was defined as the percentage of participants who achieved a best overall response of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)

18 secondary outcomes

Phase 1a: ORR
Time frame: From first dose until disease progression or death, Maximum treatment duration was 47 months.
Duration of Response (DOR)
Time frame: From first dose until disease progression or death, Maximum treatment duration was 47 months in Phase 1a and 25 months in Phase 1b.
Clinical Benefit Rate (CBR)
Time frame: From first dose until disease progression or death, Maximum treatment duration was 47 months.
Progression-free Survival (PFS)
Time frame: From first dose until disease progression or death, Maximum treatment duration was 47 months Phase 1a and 25 months in Phase 1b.
Duration of Stable Disease (DSD)
Time frame: From first dose until disease progression or death, Maximum treatment duration was 47 months Phase 1a and 25 months in Phase 1b.
Phase 1b: Disease Control Rate (DCR)
Time frame: From first dose until death, maximum treatment duration was 25 months.
Phase 1b: Overall Survival (OS)
Time frame: From first dose until death, assessed maximum treatment duration was 25 months.
Phase 1a: Trough Plasma Concentration (Ctrough) of Brimarafenib
Time frame: Predose on Cycle 1 Day 15; Cycle 2 Day 1, Cycle 3 Day 1, and Cycle 4 Day 1. Each cycle was 28 days.
Phase 1a: Area Under the Concentration-time Curve From Dosing to Time of Last Quantifiable Concentration (AUClast) of Brimarafenib
Time frame: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, and 8 hours postdose); Cycle 1 Days 2, 3, 4, 8, and 15; Cycle 2 Day 1 (predose and 1, 2, 3, 4, 6, and 8 hours postdose)
Phase 1a: Area Under the Concentration-time Curve From Dosing Time to Time Tau (Tau=24 Hours) of Brimarafenib
Time frame: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, and 24 hours postdose)
Phase 1a: Area Under the Concentration-time Curve From Dosing Extrapolated to Infinity (AUC0-inf) of Brimarafenib
Time frame: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours postdose)
Phase 1a: Maximum Observed Plasma Concentration (Cmax) of Brimarafenib
Time frame: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours postdose); Cycle 2 Day 1 (predose and 1, 2, 3, 4, 6, and 8 hours postdose)
Phase 1a: Time to Maximum Observed Plasma Concentration (Tmax) of Brimarafenib
Time frame: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, a 8, 24, 48, and 72 hours postdose); Cycle 2 Day 1 (predose and 1, 2, 3, 4, 6, and 8 hours postdose)
Phase 1a: Elimination Half-Life (t½) of Brimarafenib
Time frame: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours postdose)
Phase 1a: Apparent Oral Clearance (CL/F) of Brimarafenib
Time frame: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours postdose)
Phase 1a: Apparent Oral Volume of Distribution (Vz/F) of Brimarafenib
Time frame: Cycle 1 Day 1 (predose and 1, 2, 3, 4, 6, 8, 24, 48, and 72 hours postdose)
Phase 1b: Plasma Concentrations for Brimarafenib
Time frame: C1D1 (predose, 1, 3h postdose); C1D3, D8, D22 (±2d; predose, 2-4h postdose on D22); C2D1 (predose, 1, 3h); C3, 4, 6, 8, 10, 12 D1 and every 3rd cycle (predose); and at treatment discontinuation (2-4h).
Phase 1b: Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time frame: From first dose until 30 days after last dose of study treatment. Maximum treatment duration was 25 months.

Results and safety

Results posted to the registry on 31 Aug 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase 1a: Brimarafenib 5 mg	4	0
Phase 1a: Brimarafenib 10 mg	12	0
Phase 1a: Brimarafenib 15 mg	7	0
Phase 1a: Brimarafenib 25 mg	7	0
Phase 1a: Brimarafenib 40 mg	8	0
Phase 1a: Brimarafenib 60 mg	4	0
Phase 1b: Group 1 (Brimarafenib 25 mg)	13	0
Phase 1b: Group 1 (Brimarafenib 40 mg Randomized)	14	0
Phase 1b: Group 1 (Brimarafenib 40 mg Non-Randomized)	6	0
Phase 1b: Group 2 (Brimarafenib 40 mg)	34	0

Primary outcome: Phase 1a: Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Time frame: From first dose up to 30 days after the last dose of study treatment. Maximum treatment duration was 47 months.. Count of participants. Unit: Participants

Measure	Phase 1a: Brimarafenib 5 mg n = 4	Phase 1a: Brimarafenib 10 mg n = 12	Phase 1a: Brimarafenib 15 mg n = 7	Phase 1a: Brimarafenib 25 mg n = 7	Phase 1a: Brimarafenib 40 mg n = 8	Phase 1a: Brimarafenib 60 mg n = 4
At least one TEAE	4	12	7	7	8	4
At least one SAE	2	8	5	3	5	4

Population analysed: Safety Population

Primary outcome: Phase 1a: Maximum Tolerated Dose (MTD) of Brimarafenib

Time frame: From first dose through the end of Cycle 1 (approximately 30 days). Number. Unit: milligrams (mg) once a day (QD)

Measure	Phase 1a: Dose Escalation n = 42
Value	40

Population analysed: Safety Analysis Set

Primary outcome: Phase 1b: Recommended Phase 2 Dose (RP2D) Confirmation

Time frame: From first dose of study drug through last dose (maximum treatment duration in Phase 1b was 25 months). Number. Unit: mg

Measure	Phase 1b: Group 1 n = 67
Value	NA

Population analysed: Phase 1b Safety Population

Primary outcome: Phase 1b: Objective Response Rate (ORR)

Time frame: From first dose until disease progression or death, Maximum treatment duration was 25 months.. Number (95% Confidence Interval). Unit: Percentage of Participants

Measure	Phase 1b: Group 1 (Brimarafenib 25 mg) n = 11	Phase 1b: Group 1 (Brimarafenib 40 mg Randomized) n = 13	Phase 1b: Group 1 (Brimarafenib 40 mg Non-Randomized) n = 4	Phase 1b: Group 2 (Brimarafenib 40 mg) n = 26
Value	0 (0.0 to 28.5)	7.7 (0.2 to 36.0)	0 (0.0 to 60.2)	19.2 (6.6 to 39.4)

Population analysed: The Efficacy Evaluable Population included all dosed participants who had radiologically confirmed evaluable disease at baseline and at least 1 evaluable postbaseline radiological tumor response assessment.

18 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected from the first dose of brimarafenib through 30 days after the last dose of brimarafenib or initiation of new anticancer therapy, whichever occurred first. The maximum treatment duration was 47 months. All-cause mortality was assessed from study start through study completion (Approximately 5.5 years). Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase 1a: Brimarafenib 5 mg	2 of 4 (50%)	4 of 4 (100%)	2 of 4
Phase 1a: Brimarafenib 10 mg	8 of 12 (66.7%)	12 of 12 (100%)	5 of 12
Phase 1a: Brimarafenib 15 mg	5 of 7 (71.4%)	7 of 7 (100%)	2 of 7
Phase 1a: Brimarafenib 25 mg	3 of 7 (42.9%)	7 of 7 (100%)	2 of 7
Phase 1a: Brimarafenib 40 mg	5 of 8 (62.5%)	8 of 8 (100%)	3 of 8
Phase 1a: Brimarafenib 60 mg	4 of 4 (100%)	4 of 4 (100%)	2 of 4
Phase 1b: Group 1 (Brimarafenib 25 mg)	8 of 13 (61.5%)	12 of 13 (92.3%)	3 of 13
Phase 1b: Group 1 (Brimarafenib 40 mg Randomized)	6 of 14 (42.9%)	14 of 14 (100%)	5 of 14
Phase 1b: Group 1 (Brimarafenib 40 mg Non-Randomized)	4 of 6 (66.7%)	6 of 6 (100%)	1 of 6
Phase 1b: Group 2 (Brimarafenib 40 mg)	30 of 34 (88.2%)	34 of 34 (100%)	19 of 34

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publicationAlison M. Schram, Vivek Subbiah, Ryan Sullivan, Rasha Cosman, Jia Liu, Eric I. Sbar, Thuy Hoang, Jiarong Chen, Mark Johnson, Vincent Amoruccio, Todd Shearer, Adeela Kamal, Jocelyn Lewis, Wenlin Shao, Badreddin Edris, Lusong Luo, Jayesh Desai; Abstract CT031: 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. Cancer Res 15 April 2023; 83 (8_Supplement): CT031. https://doi.org/10.1158/1538-7445.AM2023-CT031
Individual participant dataSharing planned: Yes

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

9 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Brimarafenib in people with Solid Tumor and B-Raf Mutation-Related Tumors, run by MapKure, LLC at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1a: Number of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (time frame: From first dose up to 30 days after the last dose of study treatment. Maximum treatment duration was 47 months.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04249843, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2026.