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

Conditions

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

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

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

Study Details

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.

Key Dates

Start date

Apr 18, 2023

Status verified

Apr 2026

Primary completion

Jun 30, 2028

Completion

Jun 30, 2028

Study Design

Enrollment

554 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Part 1A: Dose Escalation NSCLC
  S241656 will be administered as a monotherapy at escalating dose levels until the biologically effective dose (BED) range is determined.
• Experimental: Part 1B: Dose Escalation GI Tumors
  S241656 will be administered as a monotherapy at escalating dose levels until the BED range is determined.
• Experimental: Part 1C: Dose Escalation PDAC
  S241656 will be administered in combination with gemcitabine/nab-paclitaxel at escalating dose levels until the BED range is determined.
• Experimental: Part 1D: Dose Escalation CRC
  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.
• Experimental: Part 1E: Dose Escalation Other Solid Tumors
  S241656 will be administered as a monotherapy at escalating dose levels until the BED range is determined.
• Experimental: Part 2A: Dose Optimization NSCLC
  S241656 will be administered to further characterize the optimal dose.
• Experimental: Part 2A1: Dose Expansion NSCLC with KRAS non-G12C mutations
  S241656 will be administered as a monotherapy in the BED range.
• Experimental: Part 2A2: Dose Expansion NSCLC with BRAF mutations
  S241656 will be administered as a monotherapy in the BED range.
• Experimental: Part 2A3: Dose Expansion NSCLC with KRAS non-G12C or BRAF mutations/alterations
  S241656 will be administered as a monotherapy in the BED range. Participants must also have active CNS metastatic disease
• Experimental: Part 2A4: Dose Expansion NSCLC with a KRAS G12C mutation
  S241656 will be administered as a monotherapy in the BED range. Participants must have received and progressed upon G12C targeted therapy
• Experimental: Part 2B1: Dose Expansion PDAC
  S241656 will be administered as a monotherapy in the BED range.
• Experimental: Part 2B2: Dose Expansion CRC
  S241656 will be administered as a monotherapy in the BED range.
• Experimental: Part 2B3: Dose Expansion BTC
  S241656 will be administered as a monotherapy in the BED range.
• Experimental: Part 2C1: Dose Expansion PDAC
  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.
• Experimental: Part 2D1: Dose Expansion CRC
  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.
• Experimental: Part 2F: Exploratory Food Effect
  S241656 will be administered as a monotherapy.

Primary Outcome Measure

Dose Escalation: Incidence of dose-limiting toxicities (DLTs) [ Time Frame: The first 28-day cycle (Cycle 1) ]

Central Contacts

• Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department
  +33 1 55 72 60 00
  [email protected]

Locations (10)

Find similar trials in Gilbert, AZ

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