NCT05786924 Phase 1/2 Trial of S241656 in Selected RAS/MAPK Mutation- Positive Malignancies
| NCT ID | NCT05786924 |
| Status | Recruiting |
| Phase | Phase 1, Phase 2 |
| Sponsor | Institut de Recherches Internationales Servier |
| Condition | Non-small Cell Lung Cancer |
| Study Type | INTERVENTIONAL |
| Enrollment | 554 participants |
| Start Date | 2023-04-18 |
| Primary Completion | 2028-06 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
Phase 1 is the earliest stage of human testing — safety and dosage are the primary focus. Visits are frequent and medical supervision is intensive. You will be among the first people to receive this treatment.
This trial targets 554 participants in total. It began in 2023-04-18 with a primary completion date of 2028-06.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
Brief 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 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.
Contact & Investigator
Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department
✉ scientificinformation@servier.com📞 +33 1 55 72 60 00
Frequently Asked Questions
Who can join the NCT05786924 clinical trial?
This trial is open to participants of all sexes, aged 18 Years or older, studying Non-small Cell Lung Cancer. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT05786924 trial and what does that mean for participants?
Phase 1 trials are the first stage of human testing. The primary goal is to assess safety and determine appropriate dosage levels. Participants are closely monitored. These trials typically involve a small number of volunteers.
Is NCT05786924 currently recruiting?
Yes, NCT05786924 is actively recruiting participants. Contact the research team at scientificinformation@servier.com for enrollment information.
Where is the NCT05786924 trial being conducted?
This trial is being conducted at Gilbert, United States, Los Angeles, United States, Los Angeles, United States, San Francisco, United States and 11 additional locations.
Who is sponsoring the NCT05786924 clinical trial?
NCT05786924 is sponsored by Institut de Recherches Internationales Servier. The trial plans to enroll 554 participants.
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