NCT05786924 · Institut de Recherches Internationales Servier
Phase 1/2 Trial of S241656 in Selected RAS/MAPK Mutation- Positive Malignancies
What this study is about
BDTX-4933-101 is a first-in-human, where both patients and doctors know the treatment given, Phase 1/2 gradually increasing doses, dose optimization and expansion study designed to evaluate the safety and how well patients handle the treatment of S241656 as treatment given alone and in combination with other anti-cancer therapies in participants with selected advanced malignancies.
View original scientific description
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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
- Gilbert, Arizona
- Los Angeles, California
- San Francisco, California
- Aurora, Colorado
- New Haven, Connecticut
- Washington D.C., District of Columbia
- Boston, Massachusetts
- Grand Rapids, Michigan
- Minneapolis, Minnesota
- St Louis, Missouri
- New York, New York
- Durham, North Carolina
And 6 more locations — see the full list below.
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Jun 17, 2026 · Source of record for eligibility and locations