2025-523474-16-00
Recruiting
Phase 2
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 IRIS14 sites in 4 countries105 target enrollmentStarted: April 17, 2026Last updated:
InterventionsBugvi 5 mg/ml pulbere pentru dispersie perfuzabilăVectibix 20 mg/ml concentrate for solution for infusionFOLINATE DE CALCIUM HIKMA 10 mg/mL, solution injectable/pour perfusionErbitux 5 mg/mL solution for infusionFluorouracil Hikma 50 mg/ml InjektionslösungIrinotecan Kabi 20 mg/ml Konzentrat zur Herstellung einer InfusionslösungOxaliplatin Kabi 5 mg/ml Konzentrat zur Herstellung einer InfusionslösungS241656 film-coated tablet 50mgS241656 film-coated tablet 25mgS241656 film-coated tablet 200mgGemcitabin Hikma 38 mg/ml Konzentrat zur Herstellung einer Infusionslösung
DrugsVectibix 20 mg/ml concentrate for solution for infusionBugvi 5 mg/ml pulbere pentru dispersie perfuzabilăFOLINATE DE CALCIUM HIKMA 10 mg/mL, solution injectable/pour perfusionErbitux 5 mg/mL solution for infusionFluorouracil Hikma 50 mg/ml InjektionslösungIrinotecan Kabi 20 mg/ml Konzentrat zur Herstellung einer InfusionslösungOxaliplatin Kabi 5 mg/ml Konzentrat zur Herstellung einer InfusionslösungS241656 film-coated tablet 50mg, S241656 film-coated tablet 25mg, S241656 film-coated tablet 200mgS241656 film-coated tablet 50mgS241656 film-coated tablet 25mgS241656 film-coated tablet 200mgGemcitabin Hikma 38 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Enrollment
- 105
- Locations
- 14
- Primary Endpoint
- Dose Escalation: Incidence of dose-limiting toxicities occurring within the first 28-day cycle Number of Adverse Events and Serious Adverse Events Dose Expansion: Objective response
Overview
Brief Summary
Dose Escalation: To evaluate the safety and tolerability of S241656 in the different indications and cumulatively when administered as monotherapy and in combination Dose Expansion: To evaluate the antitumor activity of S241656 when administered as a monotherapy and in combination
Eligibility Criteria
- Ages
- 18 years to 65+ years (65+ Years, 18-64 Years)
- Accepts Healthy Volunteers
- No
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
Exclusion Criteria
- •Cancer that has a known MEK1/2 mutation.
- •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.
- •History or current evidence of non-infectious interstitial lung disease (ILD), pneumonitis, or pulmonary fibrosis
- •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.
Arms & Interventions
Bugvi 5 mg/ml pulbere pentru dispersie perfuzabilă
Test
Intervention: Bugvi 5 mg/ml pulbere pentru dispersie perfuzabilă (Drug)
Vectibix 20 mg/ml concentrate for solution for infusion
Test
Intervention: Vectibix 20 mg/ml concentrate for solution for infusion (Drug)
FOLINATE DE CALCIUM HIKMA 10 mg/mL, solution injectable/pour perfusion
Test
Intervention: FOLINATE DE CALCIUM HIKMA 10 mg/mL, solution injectable/pour perfusion (Drug)
Erbitux 5 mg/mL solution for infusion
Test
Intervention: Erbitux 5 mg/mL solution for infusion (Drug)
Fluorouracil Hikma 50 mg/ml Injektionslösung
Test
Intervention: Fluorouracil Hikma 50 mg/ml Injektionslösung (Drug)
Irinotecan Kabi 20 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Test
Intervention: Irinotecan Kabi 20 mg/ml Konzentrat zur Herstellung einer Infusionslösung (Drug)
Oxaliplatin Kabi 5 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Test
Intervention: Oxaliplatin Kabi 5 mg/ml Konzentrat zur Herstellung einer Infusionslösung (Drug)
S241656 film-coated tablet 50mg, S241656 film-coated tablet 25mg, S241656 film-coated tablet 200mg
Test
Intervention: S241656 film-coated tablet 50mg (Drug)
S241656 film-coated tablet 50mg, S241656 film-coated tablet 25mg, S241656 film-coated tablet 200mg
Test
Intervention: S241656 film-coated tablet 25mg (Drug)
S241656 film-coated tablet 50mg, S241656 film-coated tablet 25mg, S241656 film-coated tablet 200mg
Test
Intervention: S241656 film-coated tablet 200mg (Drug)
Gemcitabin Hikma 38 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Test
Intervention: Gemcitabin Hikma 38 mg/ml Konzentrat zur Herstellung einer Infusionslösung (Drug)
Outcomes
Primary Outcomes
Dose Escalation: Incidence of dose-limiting toxicities occurring within the first 28-day cycle Number of Adverse Events and Serious Adverse Events Dose Expansion: Objective response
Dose Escalation: Incidence of dose-limiting toxicities occurring within the first 28-day cycle Number of Adverse Events and Serious Adverse Events Dose Expansion: Objective response
Secondary Outcomes
- 1. Dose Escalation: PK parameters of S241656 and its metabolite S243796, including but not limited to Cmax, tmax, AUC, and t½
- 2. Dose Escalation: Objective response Disease Control Clinical Benefit Duration of Response Time to response Progression free survival Overall survival
- 3. Dose Escalation: Clinical efficacy parameters Safety and tolerability parameters PK including: Exposure-toxicity relationship
- 4. Dose Expansion: Clinical Efficacy Parameters Safety and Tolerability Parameters PK & PD parameters
- 5. Dose Expansion: Disease Control Clinical Benefit Duration of Response Time to Response Progression free survival Overall Survival
- 6. Dose Expansion: PK parameters of S241656 and its metabolite S243796, but not limited to Cmax, tmax, AUC, and t½
Investigators
Clinical Studies Department
Scientific
Institut De Recherches Internationales Servier IRIS
Study Sites (14)
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