NCT05786924

Phase 1/2 Trial of S241656 in Selected RAS/MAPK Mutation- Positive Malignancies

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

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 554 (estimated)
• Sponsor: Institut de Recherches Internationales Servier · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Conditions

• Non-small Cell Lung Cancer
• Histiocytic Neoplasm
• Histiocytosis
• BRAF Gene Mutation
• BRAF V600E
• BRAF V600 Mutation
• BRAF Mutation-Related Tumors
• BRAF
• Metastatic Lung Non-Small Cell Carcinoma
• Metastatic Lung Cancer
• Recurrent Lung Cancer
• Recurrent Lung Non-Small Cell Carcinoma
• NSCLC
• Solid Tumor
• Solid Carcinoma
• KRAS G12D
• KRAS G12V
• KRAS Mutation-Related Tumors
• NRAS Gene Mutation
• Thyroid Cancer
• Thyroid Carcinoma
• Colorectal Cancer
• Colorectal Carcinoma
• Recurrent Histiocytic and Dendritic Cell Neoplasm
• Brain Metastases
• Recurrent NSCLC
• KRAS G13C
• Acquired Resistance to KRAS G12C Inhibitor
• KRAS G12A
• KRAS G12F
• KRAS G12R
• KRAS G13D

Interventions

Type	Name	Description
DRUG	S241656	RAF inhibitor targeting all classes of oncogenic BRAF alterations (Classes I, II, and III) and constitutively active CRAF, KRAS or NRAS mutations
DRUG	FOLFOX6/FOLFOX7	Used as a combination therapy and administered intravenously
DRUG	FOLFIRI	Used as a combination therapy and administered intravenously
DRUG	Cetuximab	Used as a combination therapy and administered intravenously
DRUG	Panitumumab	Used as a combination therapy and administered intravenously
DRUG	Gemcitabine	Used as a combination therapy and administered intravenously
DRUG	Nab-paclitaxel	Used as a combination therapy and administered intravenously

Timeline

• Start date: 2023-04-18
• Primary completion: 2028-06-01
• Completion: 2028-06-01
• First posted: 2023-03-28
• Last updated: 2025-11-20

Locations

10 sites across 1 country: United States

Regulatory

• FDA-regulated drug study