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Trial record 1 of 1 for:    NCT05786924
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A Study of BDTX-4933 in Patients With KRAS, BRAF and Select RAS/MAPK Mutation-Positive Cancers

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ClinicalTrials.gov Identifier: NCT05786924
Recruitment Status : Recruiting
First Posted : March 28, 2023
Last Update Posted : April 19, 2024
Sponsor:
Information provided by (Responsible Party):
Black Diamond Therapeutics, Inc.

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
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 Drug: BDTX-4933 Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-label Study of Oral BDTX-4933 in Patients With KRAS, BRAF and Other Select RAS/MAPK Mutation Positive Neoplasms
Actual Study Start Date : April 18, 2023
Estimated Primary Completion Date : June 2026
Estimated Study Completion Date : December 2026

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma

Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. 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

  2. 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) ]
  3. 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) ]
  4. 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) ]
  5. 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) ]

Secondary Outcome Measures :
  1. Dose Escalation/Expansion: Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Through study completion, approximately 1 year ]
  2. 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) ]
  3. 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) ]
  4. 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) ]
  5. 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) ]
  6. 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) ]
  7. 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) ]
  8. 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) ]
  9. 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) ]
  10. 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 ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05786924


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

Locations
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United States, Arizona
Banner Health- MD Anderson Cancer Center Recruiting
Gilbert, Arizona, United States, 85234
Contact: Brandi Luzania    480-256-5488    Brandi.Luzania@bannerhealth.com   
Principal Investigator: Jiaxin Niu, MD         
United States, Colorado
University of Colorado - Aurora Cancer Center Recruiting
Aurora, Colorado, United States, 80045
Contact: Halle Kuykendall    720-848-0356    halle.kuykendall@cuanschutz.edu   
United States, District of Columbia
Georgetown University Lombardi Cancer Center Recruiting
Washington, District of Columbia, United States, 20007
Contact    202-444-2223    Chul.Kim@gunet.georgetown.edu   
Principal Investigator: Chul Kim, MD         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Start Your Patient Journey to Cancer Care and Support    877-442-3324      
United States, Michigan
South Texas Accelerated Research Therapeutics (START) Midwest Recruiting
Grand Rapids, Michigan, United States, 49546
Contact: Julie Burns    616-954-5559    julie.burns@startmidwest.com   
Contact: Jade Blakeman    616-954-5551    jade.blakeman@startmidwest.com   
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Michael Offin, MD         
Contact    646-888-8538      
United States, Utah
Huntsman Cancer Institute (University of Utah) Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Emerson Lebleu    801-213-8402    emerson.lebleu@hci.utah.edu   
Principal Investigator: Sonam Puri, MD         
United States, Virginia
NEXT Virginia Recruiting
Fairfax, Virginia, United States, 22031
Contact: Blake Patterson    703-783-4505    bpatterson@nextoncology.com   
United States, Washington
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109
Contact: Rebecca Wood    206-606-6970    rwood1@seattlecca.org   
Sponsors and Collaborators
Black Diamond Therapeutics, Inc.
More Information
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Responsible Party: Black Diamond Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05786924    
Other Study ID Numbers: BDTX-4933-101
First Posted: March 28, 2023    Key Record Dates
Last Update Posted: April 19, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Black Diamond Therapeutics, Inc.:
BRAF Class I
BRAF Class II
BRAF Class III
KRAS
Intolerant histiocytic neoplasm
BDTX-4933
Phase 1
dose escalation
 dose expansion
MAPK
mitogen-activated protein kinase
RAS
RAF
Upstream oncogenic alterations
RAF inhibitor
intracranial disease
Additional relevant MeSH terms:
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Carcinoma
Neoplasms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Melanoma
Brain Neoplasms
Thyroid Neoplasms
Histiocytosis
Thyroid Diseases
Recurrence
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Disease Attributes
Pathologic Processes
 Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases