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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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

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.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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.
  • Drug: BDTX-4933
    RAF inhibitor targeting all classes of oncogenic BRAF alterations (Classes I, II, and III) and constitutively active KRAS or NRAS mutations
Experimental
Phase 1 Dose Expansion 		BDTX-4933 will be administered at the RP2D.
  • Drug: BDTX-4933
    RAF inhibitor targeting all classes of oncogenic BRAF alterations (Classes I, II, and III) and constitutively active KRAS or NRAS mutations

Recruiting Locations

Georgetown University Lombardi Cancer Center
Washington, District of Columbia 20007
Contact:
202-444-2223
Chul.Kim@gunet.georgetown.edu

More Details

Status
Recruiting
Sponsor
Black Diamond Therapeutics, Inc.

Study Contact

BDTX Clinical Trial Navigation Service
(866) 955-4397
blackdiamondtx@careboxhealth.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.