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Taking people in FrancePhase 1/2

Tests oral S241656 in adults with certain RAS or MAPK gene-mutated cancers

Tests oral S241656 in adults with lung, bowel, pancreas or bile duct cancers.

Key facts

Who runs it
Institut de Recherches Internationales Servier
Where
Dijon, Paris, Rennes, and Villejuif, FranceSee the 5 sitesAlso in 9 other countries, 44 sites
Registry title
Phase 1/2 Trial of S241656 in Selected RAS/MAPK Mutation- Positive Malignancies
Status
Recruiting
Phase
Phase 1/2
People taking part
554 people, planned
Started
18 Apr 2023
Expected to end
Jun 2028
Type of study
Interventional, 16 groups
Treatments tested
  • S241656
  • FOLFOX6/FOLFOX7
  • FOLFIRI
  • Cetuximab
  • Panitumumab
  • Gemcitabine
  • Nab-paclitaxel
Record updated
13 October 2026

Who can take part

AI summary

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for adults with advanced or metastatic solid tumors, such as lung, pancreatic, colorectal or biliary tract cancer, that carry a RAS or RAF gene change.

Age
18 years or older
Sex
All sexes can join
Disease stage
Recurrent locally advanced (unresectable) or metastatic solid tumors, confirmed by tissue or cell tests. Some parts of the trial look for non-small cell lung cancer, pancreatic, colorectal or biliary tract cancer.
Earlier treatment
Must have recovered from the side effects of earlier cancer treatment. Cannot have used experimental drugs that target the KRAS/BRAF/MEK/ERK pathway. Cannot have ongoing cancer treatment or radiation therapy.
Biomarker or test result
A documented RAS or RAF gene change (KRAS, HRAS, NRAS, BRAF and/or CRAF (RAF1) mutations or alterations).

Main reasons for not taking part

  • Cancer with a known MEK1/2 mutation
  • Clinically significant cardiovascular disease
  • Current or past retinal vein occlusion, or current risk factors for it
  • Pregnant or breastfeeding women
  • Major surgery within 4 weeks of study entry or planned during the study

The registry criteria, word for word

Show all 31 criteriaShow less

Who can take part

  • 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

Who cannot take part

  • Major surgery within 4 weeks of study entry or planned during study
  • Ongoing anticancer therapy
  • Ongoing radiation therapy
  • 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
  • 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
  • Uncontrolled or active clinically relevant bacterial, fungal, or specific viral infection requiring systemic therapy
  • Clinically significant cardiovascular disease
  • Evidence of active malignancy (other than study-specific malignancies) requiring systemic therapy within the next 2 years
  • Any contra-indication, to use of any of the combination chemotherapy or anti-EGFR therapy partners administered as part of this trial
  • Symptomatic spinal cord compression
  • History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO
  • Females who are pregnant or breastfeeding

Where in France

Also in 9 other countries, 44 sites

  • Centre Georges François LeclercDijon, FranceContact: Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies DepartmentNot yet recruiting
  • AP-HP Hopital Europeen Georges PompidouParis, FranceContact: Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies DepartmentTaking people
  • Institut CurieParis, FranceContact: Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies DepartmentNot yet recruiting
  • Centre Eugène MarquisRennes, FranceContact: Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies DepartmentTaking people
  • Institut Gustave RoussyVillejuif, FranceContact: Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies DepartmentNot yet recruiting

About the trial

What the trial wants to find out

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.

The 16 groups in the trial

  • Part 1A: Dose Escalation NSCLCTreatment being tested

    S241656 will be administered as a monotherapy at escalating dose levels until the biologically effective dose (BED) range is determined.

    Treatment: S241656

  • Part 1B: Dose Escalation GI TumorsTreatment being tested

    S241656 will be administered as a monotherapy at escalating dose levels until the BED range is determined.

    Treatment: S241656

  • Part 1C: Dose Escalation PDACTreatment being tested

    S241656 will be administered in combination with gemcitabine/nab-paclitaxel at escalating dose levels until the BED range is determined.

    Treatment: S241656, Gemcitabine, and Nab-paclitaxel

  • Part 1D: Dose Escalation CRCTreatment being tested

    S241656 will be administered in combination with FOLFOX6/FOLFOX7 or FOLFIRI, and panitumumab or cetuximab at escalating dose levels until the BED range is determined.

    Treatment: S241656, FOLFOX6/FOLFOX7, FOLFIRI, Cetuximab, and Panitumumab

  • Part 1E: Dose Escalation Other Solid TumorsTreatment being tested

    S241656 will be administered as a monotherapy at escalating dose levels until the BED range is determined.

    Treatment: S241656

  • Part 2A: Dose Optimization NSCLCTreatment being tested

    S241656 will be administered to further characterize the optimal dose.

    Treatment: S241656

  • Part 2A1: Dose Expansion NSCLC with KRAS non-G12C mutationsTreatment being tested

    S241656 will be administered as a monotherapy in the BED range.

    Treatment: S241656

  • Part 2A2: Dose Expansion NSCLC with BRAF mutationsTreatment being tested

    S241656 will be administered as a monotherapy in the BED range.

    Treatment: S241656

  • Part 2A3: Dose Expansion NSCLC with KRAS non-G12C or BRAF mutations/alterationsTreatment being tested

    S241656 will be administered as a monotherapy in the BED range. Participants must also have active CNS metastatic disease

    Treatment: S241656

  • Part 2A4: Dose Expansion NSCLC with a KRAS G12C mutationTreatment being tested

    S241656 will be administered as a monotherapy in the BED range. Participants must have received and progressed upon G12C targeted therapy

    Treatment: S241656

  • Part 2B1: Dose Expansion PDACTreatment being tested

    S241656 will be administered as a monotherapy in the BED range.

    Treatment: S241656

  • Part 2B2: Dose Expansion CRCTreatment being tested

    S241656 will be administered as a monotherapy in the BED range.

    Treatment: S241656

  • Part 2B3: Dose Expansion BTCTreatment being tested

    S241656 will be administered as a monotherapy in the BED range.

    Treatment: S241656

  • Part 2C1: Dose Expansion PDACTreatment being tested

    S241656 will be administered in combination with anti-cancer therapies in the BED range. The combination therapies to be used will be determined in the future.

    Treatment: S241656

  • Part 2D1: Dose Expansion CRCTreatment being tested

    S241656 will be administered in combination with anti-cancer therapies in the BED range. The combination therapies to be used will be determined in the future.

    Treatment: S241656

  • Part 2F: Exploratory Food EffectTreatment being tested

    S241656 will be administered as a monotherapy.

    Treatment: S241656

Questions to ask the study team

  1. How often do I need to come in, and for how long each time?
  2. Are travel costs paid?
  3. Can I keep my own doctor?
  4. What happens if I want to stop?

Contact the study team: see the registry record → Contacts and Locations

Print a page for my doctor

Data and sources

Registry record
Listed on ClinicalTrials.gov and on the EU's official list of trials (CTIS).
Official title
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
Plain-language title
Tests oral S241656 in adults with certain RAS or MAPK gene-mutated cancersGenerated from the registry record. The registry title is the official one.
AI summary
From the trial's eligibility criteria. Read by machine on 12 November 2026.
Record updated
13 October 2026