Actively Recruiting
Phase 1/2 Open-label Study of Oral S241656 Alone and Combined With Other Anti-Cancer Therapies in Patients With KRAS, BRAF, and Other RAS/MAPK Mutation-Positive Advanced Cancers
Led by Institut de Recherches Internationales Servier · Updated on 2026-04-21
554
Participants Needed
11
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are studying S241656, an oral drug targeting specific mutations in the RAS/MAPK pathway, in adults with advanced or metastatic cancers including non-small cell lung cancer (NSCLC), gastrointestinal cancers, pancreatic ductal adenocarcinoma, colorectal cancer, and biliary tract cancer. This Phase 1/2 open-label trial aims to evaluate the safety, tolerability, and optimal dosing of S241656 alone and in combination with other anti-cancer therapies for these mutation-positive malignancies. The study includes dose escalation, dose optimization, and expansion phases to understand how the drug works in different patient groups. Participants will receive S241656 orally in 28-day cycles, either alone or combined with chemotherapy regimens such as gemcitabine/nab-paclitaxel, FOLFOX6/FOLFOX7, FOLFIRI, panitumumab, or cetuximab. The dose escalation phase will identify the biologically effective dose (BED) range, followed by dose optimization or direct progression to dose expansion, depending on safety review outcomes. Combination therapies will be administered intravenously alongside S241656, and dosing will continue until disease progression, unacceptable side effects, withdrawal, or study end. Throughout the study, participants will undergo regular monitoring for side effects, dose-limiting toxicities, and response to treatment. Safety will be tracked over approximately five years, including adverse events, serious adverse events, and dose modifications. Researchers will assess tumor response and disease control using objective measures, as well as analyze pharmacokinetics of S241656 and its metabolites. Participants' health and treatment effects will be carefully evaluated through clinical assessments and laboratory tests during scheduled visits until the study concludes.
CONDITIONS
Brief Title
Phase 1/2 Trial of S241656 in Selected RAS/MAPK Mutation- Positive Malignancies
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adults aged 18 years or older
- Life expectancy of at least 12 weeks as judged by the investigator
- 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 toxicities of prior anti-cancer therapy
- Specific tumor types for dose escalation: advanced/metastatic NSCLC, GI tumors including PDAC, CRC, BTC, colorectal adenocarcinoma, and other solid tumors with relevant mutations
- Specific tumor types for dose optimization and expansion: advanced/metastatic NSCLC with KRAS non-G12C and/or BRAF mutations, advanced/metastatic PDAC, CRC, BTC with relevant mutations
You will not qualify if you...
- Presence of cancer with known MEK1/2 mutation
- Known allergy or hypersensitivity to S241656 or combination therapy agents
- Contraindications to any chemotherapy or anti-EGFR therapy used in the trial
- Major surgery within 4 weeks before study entry or planned during the study
- Ongoing anticancer or radiation therapy
- Active or uncontrolled infections requiring systemic treatment
- Clinically significant cardiovascular disease
- Symptomatic spinal cord compression
- Active malignancy other than study-specific tumors requiring systemic therapy within 2 years
- History or current retinal vein occlusion or risk factors for it
- Pregnancy or breastfeeding
- Participation in another therapeutic clinical study with systemic treatment
- Prior use of experimental agents targeting KRAS/BRAF/MEK/ERK pathways
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Repeated 28-day cycles until disease progression or discontinuation
Participants receive the study drug S241656 alone or in combination with other anti-cancer therapies. Treatment is given at escalating doses during dose escalation phases and at biologically effective doses during dose optimization and expansion phases.
Visits occur with each treatment cycle; frequency depends on treatment regimen and combination therapies
Duration - Up to approximately 5 years after treatment completion
Participants are monitored for safety and study outcomes after treatment ends.
Periodic visits for safety assessments and outcome monitoring
Trial Site Locations
Total: 11 locations
1
Banner Health- MD Anderson Cancer Center
Gilbert, Arizona, United States, 85234
Actively Recruiting
2
University of Colorado - Aurora Cancer Center
Aurora, Colorado, United States, 80045
Not Yet Recruiting
3
Georgetown University Lombardi Cancer Center
Washington D.C., District of Columbia, United States, 20007
Not Yet Recruiting
4
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Actively Recruiting
5
South Texas Accelerated Research Therapeutics (START) Midwest
Grand Rapids, Michigan, United States, 49546
Actively Recruiting
6
Masonic Cancer Center University of Minnesota
Minneapolis, Minnesota, United States, 55455
Actively Recruiting
7
Washington University
St Louis, Missouri, United States, 63130
Actively Recruiting
8
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Actively Recruiting
9
NEXT Virginia
Fairfax, Virginia, United States, 22031
Actively Recruiting
10
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
Actively Recruiting
11
National Cancer Center Hospital
Tokyo, Japan, 104-0045
Active, Not Recruiting
Research Team
I
Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
16
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