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

April 18, 2024 updated by: Black Diamond Therapeutics, Inc.

A Phase 1, Open-label Study of Oral BDTX-4933 in Patients With KRAS, BRAF and Other Select RAS/MAPK Mutation Positive Neoplasms

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

100

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Recruiting
        • Banner Health- MD Anderson Cancer Center
        • Principal Investigator:
          • Jiaxin Niu, MD
        • Contact:
    • Colorado
      • Aurora, Colorado, United States, 80045
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Recruiting
        • Georgetown University Lombardi Cancer Center
        • Principal Investigator:
          • Chul Kim, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana-Farber Cancer Institute
        • Contact:
          • Start Your Patient Journey to Cancer Care and Support
          • Phone Number: 877-442-3324
    • Michigan
      • Grand Rapids, Michigan, United States, 49546
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
          • Michael Offin, MD
        • Contact:
          • Phone Number: 646-888-8538
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute (University of Utah)
        • Principal Investigator:
          • Sonam Puri, MD
        • Contact:
    • Virginia
      • Fairfax, Virginia, United States, 22031
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Fred Hutchinson Cancer Research Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Escalation: Incidence of dose-limiting toxicities (DLTs) to estimate the preliminary RP2D and/or MTD of BDTX-4933
Time Frame: The first 28-day cycle (Cycle 1)
A DLT is defined as any event meeting the DLT criteria occurring within the first 28-day cycle
The first 28-day cycle (Cycle 1)
Dose Expansion: Objective response rate (ORR) including extracranial and intracranial
Time Frame: Day 1 of every 2 cycles to Cycle 13 Day 1, then Day 1 of every 3 cycles thereafter to study completion, approximately 1 year (each cycle is 28 days)
Day 1 of every 2 cycles to Cycle 13 Day 1, then Day 1 of every 3 cycles thereafter to study completion, approximately 1 year (each cycle is 28 days)
Dose Expansion: Duration of response (DOR)
Time Frame: Day 1 of every 2 cycles to Cycle 13 Day 1, then Day 1 of every 3 cycles thereafter to study completion, approximately 1 year (each cycle is 28 days)
Day 1 of every 2 cycles to Cycle 13 Day 1, then Day 1 of every 3 cycles thereafter to study completion, approximately 1 year (each cycle is 28 days)
Dose Expansion: Time-to-response (TTR)
Time Frame: Day 1 of every 2 cycles to Cycle 13 Day 1, then Day 1 of every 3 cycles thereafter to study completion, approximately 1 year (each cycle is 28 days)
Day 1 of every 2 cycles to Cycle 13 Day 1, then Day 1 of every 3 cycles thereafter to study completion, approximately 1 year (each cycle is 28 days)
Dose Expansion: Progression-free survival (PFS)
Time Frame: Day 1 of every 2 cycles to Cycle 13 Day 1, then Day 1 of every 3 cycles thereafter to study completion, approximately 1 year (each cycle is 28 days)
Day 1 of every 2 cycles to Cycle 13 Day 1, then Day 1 of every 3 cycles thereafter to study completion, approximately 1 year (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure
Time Frame
Dose Escalation/Expansion: Incidence and severity of treatment-emergent adverse events (TEAEs)
Time Frame: Through study completion, approximately 1 year
Through study completion, approximately 1 year
Dose Escalation/Expansion: Maximum plasma concentration (Cmax) of BDTX-4933 and its metabolite
Time Frame: Cycle 1 Days 1 and 15, Day 1 of Cycle 2 through Cycle 5, and Day 1 of every other cycle thereafter to study completion, approximately 1 year (each cycle is 28 days)
Cycle 1 Days 1 and 15, Day 1 of Cycle 2 through Cycle 5, and Day 1 of every other cycle thereafter to study completion, approximately 1 year (each cycle is 28 days)
Dose Escalation/Expansion: Time of maximum plasma concentration (Tmax) of BDTX-4933 and its metabolite
Time Frame: Cycle 1 Days 1 and 15, Day 1 of Cycle 2 through Cycle 5, and Day 1 of every other cycle thereafter to study completion, approximately 1 year (each cycle is 28 days)
Cycle 1 Days 1 and 15, Day 1 of Cycle 2 through Cycle 5, and Day 1 of every other cycle thereafter to study completion, approximately 1 year (each cycle is 28 days)
Dose Escalation/Expansion: Area under the plasma drug concentration-time curve (AUC) of BDTX-4933 and its metabolite
Time Frame: Cycle 1 Days 1 and 15, Day 1 of Cycle 2 through Cycle 5, and Day 1 of every other cycle thereafter to study completion, approximately 1 year (each cycle is 28 days)
Cycle 1 Days 1 and 15, Day 1 of Cycle 2 through Cycle 5, and Day 1 of every other cycle thereafter to study completion, approximately 1 year (each cycle is 28 days)
Dose Escalation/Expansion: Half-life (t1/2) of BDTX-4933 and its metabolite
Time Frame: Cycle 1 Days 1 and 15, Day 1 of Cycle 2 through Cycle 5, and Day 1 of every other cycle thereafter to study completion, approximately 1 year (each cycle is 28 days)
Cycle 1 Days 1 and 15, Day 1 of Cycle 2 through Cycle 5, and Day 1 of every other cycle thereafter to study completion, approximately 1 year (each cycle is 28 days)
Dose Escalation/Expansion: Overall survival
Time Frame: First dose of study drug to death due to any cause or for 12 months from last dose
First dose of study drug to death due to any cause or for 12 months from last dose
Dose Escalation: Objective response rate (ORR) including extracranial and intracranial
Time Frame: Day 1 of every 2 cycles to Cycle 13 Day 1, then Day 1 of every 3 cycles thereafter to study completion, approximately 1 year (each cycle is 28 days)
Day 1 of every 2 cycles to Cycle 13 Day 1, then Day 1 of every 3 cycles thereafter to study completion, approximately 1 year (each cycle is 28 days)
Dose Escalation: Duration of response (DOR)
Time Frame: Day 1 of every 2 cycles to Cycle 13 Day 1, then Day 1 of every 3 cycles thereafter to study completion, approximately 1 year (each cycle is 28 days)
Day 1 of every 2 cycles to Cycle 13 Day 1, then Day 1 of every 3 cycles thereafter to study completion, approximately 1 year (each cycle is 28 days)
Dose Escalation: Time to response
Time Frame: Day 1 of every 2 cycles to Cycle 13 Day 1, then Day 1 of every 3 cycles thereafter to study completion, approximately 1 year (each cycle is 28 days)
Day 1 of every 2 cycles to Cycle 13 Day 1, then Day 1 of every 3 cycles thereafter to study completion, approximately 1 year (each cycle is 28 days)
Dose Escalation: PFS
Time Frame: Day 1 of every 2 cycles to Cycle 13 Day 1, then Day 1 of every 3 cycles thereafter to study completion, approximately 1 year (each cycle is 28 days)
Day 1 of every 2 cycles to Cycle 13 Day 1, then Day 1 of every 3 cycles thereafter to study completion, approximately 1 year (each cycle is 28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Black Diamond Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 18, 2023

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

March 6, 2023

First Submitted That Met QC Criteria

March 15, 2023

First Posted (Actual)

March 28, 2023

Study Record Updates

Last Update Posted (Estimated)

April 19, 2024

Last Update Submitted That Met QC Criteria

April 18, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BDTX-4933-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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