RECRUITING

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

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Conditions

Non-small Cell Lung CancerHistiocytic NeoplasmHistiocytosisMelanomaMelanoma (Skin)BRAF Gene MutationBRAF V600EBRAF V600 MutationBRAF Mutation-Related TumorsBRAFMetastatic Lung Non-Small Cell CarcinomaMetastatic MelanomaMetastatic Lung CancerRecurrent MelanomaRecurrent Lung CancerRecurrent Lung Non-Small Cell CarcinomaNSCLCSolid TumorSolid CarcinomaKRAS G12DKRAS G12VKRAS Mutation-Related TumorsNRAS Gene MutationThyroid CancerThyroid CarcinomaColorectal CancerColorectal CarcinomaRecurrent Histiocytic and Dendritic Cell NeoplasmBrain MetastasesRecurrent NSCLCKRAS G13CAcquired Resistance to KRAS G12C InhibitorKRAS G12AKRAS G12FKRAS G12RKRAS G13DBRAF Class IBRAF Class IIBRAF Class IIIKRASIntolerant histiocytic neoplasmBDTX-4933Phase 1dose escalationdose expansionMAPKmitogen-activated protein kinaseRASRAFUpstream oncogenic alterationsRAF inhibitorintracranial diseaseCRAFNRASRAF fusions

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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, BRAF, or CRAF (RAF1) mutations, advanced/metastatic melanoma harboring BRAF or NRAS mutations, histiocytic neoplasms harboring BRAF, CRAF, 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.

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

Quick Facts

Study Start:2023-04-18
Study Completion:2026-12
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05786924

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.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. 1. Disease criteria:
  2. 1. Histologically or cytologically confirmed recurrent/advanced (unresectable) or metastatic solid tumors or histiocytic neoplasms with documented RAS or BRAF mutations.
  3. 2. Dose Escalation cohorts:
  4. * NSCLC with KRAS non-G12C mutations, including other mutations at KRAS-G12 (eg, G12V/G12D) and other oncogenic variants of KRAS mutations on G13 and Q61 amino acid residues, BRAF, or CRAF mutations.
  5. * Melanoma with BRAF, CRAF, or NRAS mutations.
  6. * Histiocytic neoplasms with BRAF or NRAS mutations.
  7. * Thyroid carcinoma with BRAF mutations.
  8. * Colorectal carcinoma with BRAF (Class II or III) mutations with Sponsor approval.
  9. * Other solid tumors with BRAF Class I mutations after prior treatment with a BRAF/MEK inhibitor or local standard-of-care with Sponsor approval.
  10. 3. Dose Expansion cohort:
  11. 2. Prior standard-of-care
  12. 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.
  13. 2. Patients with eligible tumors harboring BRAF V600E mutations must have received FDA approved BRAF targeted therapy, BRAF/MEK inhibitors combination, or BRAF inhibitors combination.
  14. 3. Evaluable or measurable disease in dose escalation and measurable disease only for dose expansion cohorts.
  15. 4. Adequate bone marrow and organ function.
  16. 5. Recovered from toxicity to prior anti-cancer therapy.
  17. 6. Appropriate candidate for BDTX-4933 monotherapy.
  18. 7. Life expectancy of \>=12 weeks in the opinion of the Investigator.
  1. 1. Cancer that has a known MEK1/2 mutation.
  2. 2. Major surgery within 4 weeks of study entry or planned during study.
  3. 3. Ongoing anticancer therapy.
  4. 4. Ongoing radiation therapy.
  5. 5. Uncontrolled or active clinically relevant bacterial, fungal, or specific viral infection requiring systemic therapy.
  6. 6. Symptomatic spinal cord compression.
  7. 7. Evidence of active malignancy (other than study-specific malignancies) requiring systemic therapy within the next 2 years.
  8. 8. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
  9. 9. Females who are pregnant or breastfeeding.
  10. 10. Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study.
  11. 11. Prior use of experimental agents that target the KRAS/BRAF/MEK/ERK pathway.

Contacts and Locations

Study Contact

Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department
CONTACT
+33 1 55 72 60 00
scientificinformation@servier.com

Study Locations (Sites)

Banner Health- MD Anderson Cancer Center
Gilbert, Arizona, 85234
United States
University of Colorado - Aurora Cancer Center
Aurora, Colorado, 80045
United States
Georgetown University Lombardi Cancer Center
Washington, District of Columbia, 20007
United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
United States
South Texas Accelerated Research Therapeutics (START) Midwest
Grand Rapids, Michigan, 49546
United States
Masonic Cancer Center University of Minnesota
Minneapolis, Minnesota, 55455
United States
Washington University
Saint Louis, Missouri, 63130
United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
United States
NEXT Virginia
Fairfax, Virginia, 22031
United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
United States

Collaborators and Investigators

Sponsor: Institut de Recherches Internationales Servier

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 Registration Dates

Study Start Date2023-04-18
Study Completion Date2026-12

Study Record Updates

Study Start Date2023-04-18
Study Completion Date2026-12

Terms related to this study

Keywords Provided by Researchers

  • 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
  • CRAF
  • NRAS
  • RAF fusions

Additional Relevant MeSH Terms

  • 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
  • Acquired Resistance to KRAS G12C Inhibitor
  • KRAS G12A
  • KRAS G12F
  • KRAS G12R
  • KRAS G13D