A Study of BDTX-4933 in Patients With KRAS, BRAF and Select RAS/MAPK Mutation-Positive Cancers

Study Purpose

BDTX-4933-101 is a first-in-human, open-label, Phase 1 dose escalation and an expansion cohort study designed to evaluate the safety and tolerability, maximum tolerated dose (MTD) and the preliminary recommended Phase 2 dose (RP2D), and antitumor activity of BDTX-4933. The study population for the Dose Escalation part of the study comprises adults with recurrent advanced/metastatic non-small cell lung cancer (NSCLC) harboring KRAS non-G12C mutations or BRAF mutations, advanced/metastatic melanoma harboring BRAF or NRAS mutations, histiocytic neoplasms harboring BRAF or NRAS mutations, and other solid tumors harboring BRAF mutations. The study population for the Dose Expansion part of the study comprises adults with recurrent advanced/metastatic NSCLC harboring KRAS non-G12C mutations. All patients will self-administer BDTX-4933 orally in 28-day cycles until disease progression, toxicity, withdrawal of consent, or termination of the study.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Key

Inclusion Criteria:

1. Disease criteria: 1. Histologically or cytologically confirmed recurrent/advanced (unresectable) or metastatic solid tumors or histiocytic neoplasms with documented RAS or BRAF mutations. Note: Patients may have stable central nervous system (CNS) metastases. Patients with active CNS metastases or primary CNS tumors associated with progressive neurological symptoms or needing increased doses of corticosteroids to control the CNS disease are excluded from the study. 2. Dose Escalation cohorts:
  • - NSCLC with KRAS non-G12C mutations, including other mutations at KRAS-G12 (eg, G12V/G12D) or BRAF (Class I, II, or III) (with Sponsor approval).
  • - Melanoma with BRAF (Class I, II, or III) or NRAS mutations.
  • - Histiocytic neoplasms with BRAF (Class I, II, or III) or NRAS mutations.
  • - Thyroid carcinoma with BRAF (Class I, II, or III) mutations.
  • - Colorectal carcinoma with BRAF (Class II or III) mutations with Sponsor approval.
  • - Other solid tumors with BRAF Class I mutations after prior treatment with a BRAF/MEK inhibitor or local standard-of-care with Sponsor approval.
3. Dose Expansion cohort: Recurrent advanced/metastatic NSCLC with KRAS non-G12C mutations without small cell lung cancer transformation with progressive disease confirmed by radiographic assessment. 2. Received prior standard-of-care: 1. Exhausted all available standard-of-care therapies or, in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from available standard-of-care therapy. 2. Patients with eligible tumors harboring BRAF V600E mutations that have received FDA approved BRAF targeted therapy, BRAF/MEK inhibitors combination, or BRAF inhibitors combination. 3. Evaluable or measurable disease in dose escalation and measurable disease only for dose expansion cohorts. 4. Adequate bone marrow and organ function. 5. Recovered from toxicity to prior anti-cancer therapy. 6. Appropriate candidate for BDTX-4933 monotherapy. 7. Life expectancy of >=12 weeks in the opinion of the Investigator. Key

Exclusion Criteria:

1. Cancer that has a known MEK1/2 mutation. 2. Major surgery within 4 weeks of study entry or planned during study. 3. Ongoing anticancer therapy. 4. Ongoing radiation therapy. 5. Uncontrolled or active clinically relevant bacterial, fungal, or specific viral infection requiring systemic therapy. 6. Symptomatic spinal cord compression. 7. Evidence of active malignancy (other than study-specific malignancies) requiring systemic therapy within the next 2 years. 8. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO. 9. Females who are pregnant or breastfeeding. 10. Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study. 11. Prior use of experimental agents that target the KRAS/BRAF/MEK/ERK pathway.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT05786924
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Black Diamond Therapeutics, Inc.
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Non-small Cell Lung Cancer, Histiocytic Neoplasm, Histiocytosis, Melanoma, Melanoma (Skin), BRAF Gene Mutation, BRAF V600E, BRAF V600 Mutation, BRAF Mutation-Related Tumors, BRAF, Metastatic Lung Non-Small Cell Carcinoma, Metastatic Melanoma, Metastatic Lung Cancer, Recurrent Melanoma, Recurrent Lung Cancer, Recurrent Lung Non-Small Cell Carcinoma, NSCLC, Solid Tumor, Solid Carcinoma, KRAS G12D, KRAS G12V, KRAS Mutation-Related Tumors, NRAS Gene Mutation, Thyroid Cancer, Thyroid Carcinoma, Colorectal Cancer, Colorectal Carcinoma, Recurrent Histiocytic and Dendritic Cell Neoplasm, Brain Metastases, Recurrent NSCLC, KRAS G13C
Arms & Interventions

Arms

Experimental: Phase 1 Dose Escalation

BDTX-4933 will be administered at escalating dose levels until the maximum tolerated dose (MTD) is reached and the preliminary recommended Phase 2 dose (RP2D) is determined.

Experimental: Phase 1 Dose Expansion

BDTX-4933 will be administered at the RP2D.

Interventions

Drug: - BDTX-4933

RAF inhibitor targeting all classes of oncogenic BRAF alterations (Classes I, II, and III) and constitutively active KRAS or NRAS mutations

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Banner Health- MD Anderson Cancer Center, Gilbert, Arizona

Status

Recruiting

Address

Banner Health- MD Anderson Cancer Center

Gilbert, Arizona, 85234

Site Contact

Brandi Luzania

[email protected]

480-256-5488

Cedars Sinai Medical Center, Los Angeles, California

Status

Recruiting

Address

Cedars Sinai Medical Center

Los Angeles, California, 90048

Site Contact

Garrett Crook

[email protected]

424-314-0745

Aurora, Colorado

Status

Recruiting

Address

University of Colorado - Aurora Cancer Center

Aurora, Colorado, 80045

Site Contact

Halle Kuykendall

[email protected]

720-848-0356

Washington, District of Columbia

Status

Recruiting

Address

Georgetown University Lombardi Cancer Center

Washington, District of Columbia, 20007

Dana-Farber Cancer Institute, Boston, Massachusetts

Status

Recruiting

Address

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

Site Contact

Start Your Patient Journey to Cancer Care and Support

[email protected]

877-442-3324

Grand Rapids, Michigan

Status

Recruiting

Address

South Texas Accelerated Research Therapeutics (START) Midwest

Grand Rapids, Michigan, 49546

Site Contact

Julie Burns

[email protected]

616-954-5559

Memorial Sloan Kettering Cancer Center, New York, New York

Status

Recruiting

Address

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Site Contact

Michael Offin, MD

[email protected]

(866) 955-4397

Salt Lake City, Utah

Status

Recruiting

Address

Huntsman Cancer Institute (University of Utah)

Salt Lake City, Utah, 84112

Site Contact

Emerson Lebleu

[email protected]

801-213-8402

NEXT Virginia, Fairfax, Virginia

Status

Recruiting

Address

NEXT Virginia

Fairfax, Virginia, 22031

Site Contact

Blake Patterson

[email protected]

703-783-4505

Fred Hutchinson Cancer Research Center, Seattle, Washington

Status

Recruiting

Address

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109

Site Contact

Rebecca Wood

[email protected]

206-606-6970

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