S-241656 for Malignant solid tumor|RAS/MAPK mutation-positive malignancies

Inclusion criteria

• {"criterion_text":"- 1. Life expectancy of ≥ 12 weeks in the opinion of the investigator"}
• {"criterion_text":"- 2. Histologically or cytologically confirmed recurrent locally advanced (unresectable) or metastatic solid tumors with documented RAS or RAF mutations or alterations."}
• {"criterion_text":"- 3. Adequate bone marrow and organ function."}
• {"criterion_text":"- 4. Recovered from toxicity to prior anti-cancer therapy."}
• {"criterion_text":"- 5. 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"}
• {"criterion_text":"- 6. 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

• {"criterion_text":"- 1. Cancer that has a known MEK1/2 mutation."}
• {"criterion_text":"- 5. Ongoing anticancer therapy."}
• {"criterion_text":"- 6. Ongoing radiation therapy."}
• {"criterion_text":"- 7. Uncontrolled or active clinically relevant bacterial, fungal, or specific viral infection requiring systemic therapy."}
• {"criterion_text":"- 8. Clinically significant cardiovascular disease."}
• {"criterion_text":"- 9. Symptomatic spinal cord compression."}
• {"criterion_text":"- 15. History or current evidence of non-infectious interstitial lung disease (ILD), pneumonitis, or pulmonary fibrosis"}
• {"criterion_text":"- 10. Evidence of active malignancy (other than study-specific malignancies) requiring systemic therapy within the next 2 years."}
• {"criterion_text":"- 11. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO."}
• {"criterion_text":"- 12. Females who are pregnant or breastfeeding."}
• {"criterion_text":"- 13. Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study."}
• {"criterion_text":"- 14. Prior use of experimental agents that target the KRAS/BRAF/MEK/ERK pathway."}
• {"criterion_text":"- 2. Known allergy/hypersensitivity to excipients of S241656 or to any of the registered IMPs administered in combination."}
• {"criterion_text":"- 3. Any contra-indication, to use of any of the combination chemotherapy or anti-EGFR therapy partners administered as part of this trial."}
• {"criterion_text":"- 4. Major surgery within 4 weeks of study entry or planned during study."}

Primary endpoints

• {"endpoint_text":"- Dose Escalation: Incidence of dose-limiting toxicities occurring within the first 28-day cycle\n- Number of Adverse Events and Serious Adverse Events\n- Dose Expansion: Objective response","definition_or_measurement_approach":"Dose-limiting toxicities occurring within the first 28-day cycle (time window specified); counting of adverse events and serious adverse events; objective response for dose expansion. No further measurement definitions or assessment criteria are provided in the CTIS metadata."}

Secondary endpoints

• {"endpoint_text":"- 1. Dose Escalation: PK parameters of S241656 and its metabolite S243796, including but not limited to Cmax, tmax, AUC, and t½","definition_or_measurement_approach":"Pharmacokinetic parameters (Cmax, tmax, AUC, t½) measured in plasma for S241656 and metabolite S243796 as listed."}
• {"endpoint_text":"- 2. Dose Escalation: Objective response Disease Control Clinical Benefit Duration of Response Time to response Progression free survival Overall survival","definition_or_measurement_approach":"Tumor response and clinical efficacy endpoints (objective response, disease control, clinical benefit, duration of response, time to response, progression-free survival, overall survival) listed; specific assessment criteria (e.g., RECIST) not specified in CTIS metadata."}
• {"endpoint_text":"- 3. Dose Escalation: Clinical efficacy parameters Safety and tolerability parameters PK including: Exposure-toxicity relationship","definition_or_measurement_approach":"Clinical efficacy and safety/tolerability assessments and PK analyses including exposure-toxicity relationship; no further definition provided."}
• {"endpoint_text":"- 4. Dose Expansion: Clinical Efficacy Parameters Safety and Tolerability Parameters PK & PD parameters","definition_or_measurement_approach":"Clinical efficacy, safety/tolerability, and PK/PD parameter assessments for dose expansion cohorts; definitions not provided."}
• {"endpoint_text":"- 5. Dose Expansion: Disease Control Clinical Benefit Duration of Response Time to Response Progression free survival Overall Survival","definition_or_measurement_approach":"Efficacy endpoints for dose expansion: disease control, clinical benefit, duration of response, time to response, PFS, OS; measurement methods not specified."}
• {"endpoint_text":"- 6. Dose Expansion: PK parameters of S241656 and its metabolite S243796, but not limited to Cmax, tmax, AUC, and t½","definition_or_measurement_approach":"PK parameters of S241656 and metabolite S243796 (Cmax, tmax, AUC, t½) measured in plasma."}

Denmark

Earliest CTIS Part Ii Submission Date

02-04-2026

Latest Decision Or Authorization Date

21-04-2026

Processing Time Days

19

Number Of Sites

1

Number Of Participants

15

France

Earliest CTIS Part Ii Submission Date

10-02-2026

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

71

Number Of Sites

4

Number Of Participants

30

Italy

Earliest CTIS Part Ii Submission Date

07-04-2026

Latest Decision Or Authorization Date

22-04-2026

Processing Time Days

15

Number Of Sites

4

Number Of Participants

30

Spain

Earliest CTIS Part Ii Submission Date

01-04-2026

Latest Decision Or Authorization Date

24-04-2026

Processing Time Days

23

Number Of Sites

5

Number Of Participants

30

Primary sponsor

Full Name

Institut De Recherches Internationales Servier IRIS

Organisation Type

Pharmaceutical company

Country Of Registered Address

France

Contract research organisations

Name

Medpace Finland Oy

Responsibilities

Sponsor duties codes: 1,11,12,13,15 (patient recruitment),4,5,6; contact RS-Advisor-Support@medpace.com

Name

Charles River Laboratories Inc.

Responsibilities

Sponsor duties code: 4; contact supplier.care@crl.com

Name

Endpoint Clinical Inc.

Responsibilities

Sponsor duties code: 3; contact support@endpointclinical.com

Name

Medidata Solutions Inc.

Responsibilities

Sponsor duties code: 6; contact helpdesk@mdsol.com

Third parties

• {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"Sponsor duties codes: 4; contact email: clientservices.trials@guardanthealth.com","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Spain","full_name":"Taxi Travel Ticket S.L.","duties_or_roles":"Patient travel reimbursement","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"Sponsor duties codes: 1,11,12,13,15 (patient recruitment),4,5,6; contact email: RS-Advisor-Support@medpace.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Charles River Laboratories Inc.","duties_or_roles":"Sponsor duties codes: 4; contact email: supplier.care@crl.com","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Transperfect Translations International Inc.","duties_or_roles":"Eligibility vendor","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Sponsor duties code: 6 (electronic data capture/support)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"Sponsor duties code: 14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"Sponsor duties code: 3","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Pharmaspecific","duties_or_roles":"Patient travel reimbursement","organisation_type":"Pharmaceutical company"}