Evaluating BDTX-4933 for patients with specific cancer mutations
A Phase 1/2, Open-label Study of Oral S241656 (BDTX-4933) as Monotherapy and in Combination With Other Anti-Cancer Therapies in Patients With KRAS, BRAF and Other Selected RAS/MAPK Mutation-Positive Malignancies
PHASE1; PHASE2 · Servier · NCT05786924
This study is testing a new drug called BDTX-4933 to see if it can help adults with advanced cancers that have certain gene mutations feel better and improve their treatment options.
Quick facts
| Phase | PHASE1; PHASE2 |
|---|---|
| Study type | Interventional |
| Enrollment | 554 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Servier (industry) |
| Drugs / interventions | chemotherapy, radiation |
| Locations | 11 sites (Gilbert, Arizona and 10 other locations) |
| Trial ID | NCT05786924 on ClinicalTrials.gov |
What this trial studies
This Phase 1 clinical trial investigates the safety, tolerability, and preliminary effectiveness of BDTX-4933 in adults with advanced or metastatic cancers that have specific mutations in the KRAS, BRAF, or NRAS genes. The study consists of a dose escalation phase to determine the maximum tolerated dose and an expansion cohort focusing on non-small cell lung cancer with KRAS non-G12C mutations. Patients will take BDTX-4933 orally in 28-day cycles until their disease progresses or they choose to withdraw. The trial aims to provide insights into the drug's antitumor activity in these mutation-positive cancers.
Who should consider this trial
Good fit: Ideal candidates include adults with recurrent advanced or metastatic solid tumors or histiocytic neoplasms that have documented RAS or BRAF mutations.
Not a fit: Patients with active central nervous system metastases or primary CNS tumors with progressive neurological symptoms are unlikely to benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could offer a new therapeutic option for patients with specific mutation-positive cancers that currently have limited treatment options.
How similar studies have performed: Other studies targeting similar mutations in cancers have shown promising results, suggesting that this approach may be effective.
Eligibility criteria
Show full inclusion / exclusion criteria
Key Inclusion Criteria: * Life expectancy of ≥ 12 weeks in the opinion of the investigator. * Histologically or cytologically confirmed recurrent locally advanced (unresectable) or metastatic solid tumors with documented RAS or RAF mutations or alterations. * Adequate bone marrow and organ function. * Recovered from toxicity to prior anti-cancer therapy. Part 1 Dose Escalation cohort ONLY: * Part 1A: Advanced/metastatic NSCLC with KRAS non-G12C, HRAS, NRAS, BRAF or CRAF (RAF1) mutations or alterations * Part 1B: Advanced/metastatic GI tumors (e.g., PDAC, CRC, and BTC) with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations * Part 1C: Advanced/metastatic PDAC with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations * Part 1D: Colorectal adenocarcinoma with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations * Part 1E: Other advanced/metastatic non-GI, non-NSCLC solid tumors with KRAS, HRAS, NRAS, BRAF, CRAF (RAF1) mutations or alterations Part 2 Dose Optimization and Expansion cohorts ONLY: * Part 2A: Advanced/metastatic NSCLC with KRAS non-G12C mutations and/or BRAF mutations * Part 2A1: Advanced/metastatic NSCLC with KRAS non-G12C mutations * Part 2A2: Advanced/metastatic NSCLC with BRAF mutations * Part 2A3: Advanced/metastatic NSCLC with KRAS non-G12C or BRAF mutations or alterations and active CNS metastatic disease * Part 2A4: Advanced/metastatic NSCLC with a KRAS G12C mutation * Part 2B1: Advanced/metastatic PDAC with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations * Part 2B2: Advanced/metastatic CRC with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations * Part 2B3: Advanced/metastatic BTC (adenocarcinoma) with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations Key Exclusion Criteria: * Cancer that has a known MEK1/2 mutation. * Known allergy/hypersensitivity to excipients of S241656 or to any of the registered IMPs administered in combination. * Any contra-indication, to use of any of the combination chemotherapy or anti-EGFR therapy partners administered as part of this trial. * Major surgery within 4 weeks of study entry or planned during study. * Ongoing anticancer therapy. * Ongoing radiation therapy. * Uncontrolled or active clinically relevant bacterial, fungal, or specific viral infection requiring systemic therapy. * Clinically significant cardiovascular disease. * Symptomatic spinal cord compression. * Evidence of active malignancy (other than study-specific malignancies) requiring systemic therapy within the next 2 years. * History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO. * Females who are pregnant or breastfeeding. * Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study. * Prior use of experimental agents that target the KRAS/BRAF/MEK/ERK pathway.
Where this trial is running
Gilbert, Arizona and 10 other locations
- Banner Health- MD Anderson Cancer Center — Gilbert, Arizona, United States (RECRUITING)
- University of Colorado - Aurora Cancer Center — Aurora, Colorado, United States (NOT_YET_RECRUITING)
- Georgetown University Lombardi Cancer Center — Washington D.C., District of Columbia, United States (NOT_YET_RECRUITING)
- Dana-Farber Cancer Institute — Boston, Massachusetts, United States (RECRUITING)
- South Texas Accelerated Research Therapeutics (START) Midwest — Grand Rapids, Michigan, United States (RECRUITING)
- Masonic Cancer Center University of Minnesota — Minneapolis, Minnesota, United States (RECRUITING)
- Washington University — St Louis, Missouri, United States (RECRUITING)
- Memorial Sloan Kettering Cancer Center — New York, New York, United States (RECRUITING)
- NEXT Virginia — Fairfax, Virginia, United States (RECRUITING)
- Fred Hutchinson Cancer Research Center — Seattle, Washington, United States (RECRUITING)
- National Cancer Center Hospital — Tokyo, Japan (ACTIVE_NOT_RECRUITING)
Study contacts
- Study coordinator: Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department
- Email: scientificinformation@servier.com
- Phone: +33 1 55 72 60 00
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions: Non-small Cell Lung Cancer, Histiocytic Neoplasm, Histiocytosis, BRAF Gene Mutation, BRAF V600E, BRAF V600 Mutation, BRAF Mutation-Related Tumors, BRAF