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
Institut de Recherches Internationales Servier
Summary
BDTX-4933-101 is a first-in-human, open-label, Phase 1/2 dose escalation, dose optimization and expansion study designed to evaluate the safety and tolerability of S241656 as monotherapy and in combination with other anti-cancer therapies in participants with selected advanced malignancies. The study population for the Dose Escalation part of the study comprises adults with recurrent advanced/metastatic non-small cell lung cancer (NSCLC), Gastrointestinal (GI) cancers, and other solid tumors harboring KRAS, HRAS, NRAS, BRAF, and/or CRAF (Rapidly Accelerated Fibrosarcoma (RAF1)) mutations or alterations. A dose optimization part in adults with NSCLC may follow the dose escalation phase if the sponsor, in consultation with the safety review committee, decides it is necessary to further characterize the optimal dose. However, the study may also proceed directly to the expansion phase. The study population for the Dose Expansion part of the study comprises adults with advanced/metastatic NSCLC with KRAS and/or BRAF mutations, and with Pancreatic Ductal AdenoCarcinoma (PDAC), ColoRectal Cancer (CRC), and Biliary Tract Cancer (BTC) with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations and alterations. All patients will self-administer S241656 orally in 28-day cycles until disease progression, toxicity, withdrawal of consent, or termination of the study.
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
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,…
Interventions
- DrugS241656
RAF inhibitor targeting all classes of oncogenic BRAF alterations (Classes I, II, and III) and constitutively active CRAF, KRAS or NRAS mutations
- DrugFOLFOX6/FOLFOX7
Used as a combination therapy and administered intravenously
- DrugFOLFIRI
Used as a combination therapy and administered intravenously
- DrugCetuximab
Used as a combination therapy and administered intravenously
- DrugPanitumumab
Used as a combination therapy and administered intravenously
- DrugGemcitabine
Used as a combination therapy and administered intravenously
- Drug
Locations (11)
- Banner Health- MD Anderson Cancer CenterGilbert, Arizona
- University of Colorado - Aurora Cancer CenterAurora, Colorado
- Georgetown University Lombardi Cancer CenterWashington D.C., District of Columbia
- Dana-Farber Cancer InstituteBoston, Massachusetts
- South Texas Accelerated Research Therapeutics (START) MidwestGrand Rapids, Michigan
- Masonic Cancer Center University of MinnesotaMinneapolis, Minnesota