A Phase 1/2 interventional study of S241656 and FOLFOX6/FOLFOX7 in Non-small Cell Lung Cancer, Histiocytic Neoplasm and Histiocytosis, sponsored by Institut de Recherches Internationales Servier. Recruiting at 49 sites in 10 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-13.
Sponsored by Institut de Recherches Internationales Servier · Phase 1/2, Interventional, and Treatment
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.
7,620 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,838 are open to participants now.
This study's planned enrollment of 554 is above the median of 62 across 6,019 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.
Browse Carcinoma, Non-Small-Cell Lung studies →Institut de Recherches Internationales Servier is the lead sponsor of 67 studies on the registry; 4 are open to participants now.
Of its 18 completed or terminated interventional studies of FDA-regulated products, 9 (50%) have results posted.
Counted across the registry records on this site, refreshed daily.
Key Inclusion Criteria:
Part 1 Dose Escalation cohort ONLY:
Part 2 Dose Optimization and Expansion cohorts ONLY:
Key Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
S241656 will be administered as a monotherapy at escalating dose levels until the biologically effective dose (BED) range is determined.
Drug: S241656
S241656 will be administered as a monotherapy at escalating dose levels until the BED range is determined.
Drug: S241656
S241656 will be administered in combination with gemcitabine/nab-paclitaxel at escalating dose levels until the BED range is determined.
Drug: S241656 · Drug: Gemcitabine · Drug: Nab-paclitaxel
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.
Drug: S241656 · Drug: FOLFOX6/FOLFOX7 · Drug: FOLFIRI · Drug: Cetuximab · Drug: Panitumumab
S241656 will be administered as a monotherapy at escalating dose levels until the BED range is determined.
Drug: S241656
S241656 will be administered to further characterize the optimal dose.
Drug: S241656
S241656 will be administered as a monotherapy in the BED range.
Drug: S241656
S241656 will be administered as a monotherapy in the BED range.
Drug: S241656
S241656 will be administered as a monotherapy in the BED range. Participants must also have active CNS metastatic disease
Drug: S241656
S241656 will be administered as a monotherapy in the BED range. Participants must have received and progressed upon G12C targeted therapy
Drug: S241656
S241656 will be administered as a monotherapy in the BED range.
Drug: S241656
S241656 will be administered as a monotherapy in the BED range.
Drug: S241656
S241656 will be administered as a monotherapy in the BED range.
Drug: S241656
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.
Drug: S241656
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.
Drug: S241656
S241656 will be administered as a monotherapy.
Drug: S241656
RAF inhibitor targeting all classes of oncogenic BRAF alterations (Classes I, II, and III) and constitutively active CRAF, KRAS or NRAS mutations
Also known as: BDTX-4933
Used as a combination therapy and administered intravenously
Used as a combination therapy and administered intravenously
Used as a combination therapy and administered intravenously
Used as a combination therapy and administered intravenously
Used as a combination therapy and administered intravenously
Used as a combination therapy and administered intravenously
Dose Escalation: Incidence of dose-limiting toxicities (DLTs)
A DLT is defined as any event meeting the DLT criteria occurring within the first 28-day cycle
Time frame: The first 28-day cycle (Cycle 1)
Dose Escalation: Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Through study completion, approximately 5 years
Dose Optimization/Expansion: Objective response (OR)
Time frame: Through study completion, approximately 5 years
Dose Escalation/Expansion: Incidence and severity of treatment-emergent adverse events (TEAEs)
Time frame: Through study completion, approximately 5 years
Dose Escalation/Optimization/Expansion: Maximum plasma concentration (Cmax) of S241656 and its metabolite S243796
Time frame: Through study completion, approximately 5 years
Dose Escalation/Optimization/Expansion: Time of maximum plasma concentration (Tmax) of S241656 and its metabolite S243796
Time frame: Through study completion, approximately 5 years
Dose Escalation/Optimization/Expansion: Area under the plasma drug concentration-time curve (AUC) of S241656 and its metabolite S243796
Time frame: Through study completion, approximately 5 years
Dose Escalation/Optimization/Expansion: Half-life (t1/2) of S241656 and its metabolite S243796
Time frame: Through study completion, approximately 5 years
Dose Escalation: Objective response (OR)
Time frame: Through study completion, approximately 5 years
Dose Escalation/Optimization/Expansion: Disease Control (DC)
Time frame: Through study completion, approximately 5 years
Dose Escalation/Optimization/Expansion: Clinical Benefit (CB)
Time frame: Through study completion, approximately 5 years
Dose Escalation/Optimization/Expansion: Duration of response (DOR)
Time frame: Through study completion, approximately 5 years
Dose Escalation/Optimization/Expansion: Time to response (TTR)
Time frame: Through study completion, approximately 5 years
Dose Escalation/Optimization/Expansion: Progression-free Survival (PFS)
Time frame: Through study completion, approximately 5 years
Dose Escalation/Optimization/Expansion: Overall survival (OS)
Time frame: Through study completion, approximately 5 years
Dose Optimization/Expansion: Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Through study completion, approximately 5 years
Dose Escalation/Optimization/Expansion: Number of Dose Interruptions
Time frame: Through study completion, approximately 5 years
Dose Escalation/Optimization/Expansion: Number of Dose Reductions
Time frame: Through study completion, approximately 5 years
Dose Escalation: Number of Dose Discontinuations
Time frame: Through study completion, approximately 5 years
Dose Optimization/Expansion: Changes in allelic fraction of DNA sequence variants detected in ctDNA from baseline to on-treatment time points
Time frame: Through study completion, approximately 5 years
Plan to share: No
No publications or documents are linked to this record.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Carcinoma, Non-Small-Cell Lung →
Institut de Recherches Internationales Servier