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

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

• KRAS G13C
• 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
• Acquired Resistance to KRAS G12C Inhibitor
• KRAS G12A
• KRAS G12F
• KRAS G12R
• KRAS G13D

Interventions

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

Sponsors & Collaborators

• Institut de Recherches Internationales Servier

  lead OTHER

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-04-18

Primary Completion

2028-06-30

Completion

2028-06-30

FDA Drug

Yes

Countries

• United States
• Japan

Study Locations