Phase 1/2 Trial of S241656 in Selected RAS/MAPK Mutation- Positive Malignancies
a study on Lung Cancer Non-Small Cell Lung Cancer Histiocytic Neoplasm Histiocytosis BRAF Gene Mutation BRAF V600E BRAF V600 Mutation BRAF Mutation-Related Tumors BRAF Small Cell Carcinoma Solid Tumor Solid Carcinoma KRAS G12D KRAS G12V KRAS Mutation-Related Tumors NRAS Gene Mutation Thyroid Cancer Colorectal Cancer Histiocytic and Dendritic Cell Neoplasm Brain Cancer KRAS G13C Acquired Resistance to KRAS G12C Inhibitor KRAS G12A KRAS G12F KRAS G12R KRAS G13D Lung Tumor Colorectal Tumor Brain Tumor
Summary
- Eligibility
- for people ages 18 years and up (full criteria)
- Location
- at UCSF
- Dates
- study startedstudy ends around
- Principal Investigator
- by Varun Monga (ucsf)
Description
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.
Official Title
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
Keywords
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, BRAF Class I, BRAF Class II, BRAF Class III, KRAS, Intolerant histiocytic neoplasm, BDTX-4933, Phase 1, dose escalation, dose expansion, MAPK, mitogen-activated protein kinase, RAS, RAF, Upstream oncogenic alterations, RAF inhibitor, intracranial disease, CRAF, NRAS, RAF fusions, Non-Small-Cell Lung Carcinoma, Lung Neoplasms, Thyroid Neoplasms, Colorectal Neoplasms, Brain Neoplasms, IFL protocol, Cetuximab, Panitumumab, Gemcitabine, 130-nm albumin-bound paclitaxel, FOLFOX6/FOLFOX7, FOLFIRI, Nab-paclitaxel
Eligibility
You can join if…
Open to people ages 18 years and up
- Life expectancy of ≥ 12 weeks in the opinion of the investigator.
- Histologically or cytologically 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 toxicity to prior anti-cancer therapy.
Part 1 Dose Escalation cohort ONLY:
- Part 1A: Advanced/metastatic NSCLC with KRAS non-G12C, HRAS, NRAS, BRAF or CRAF (RAF1) mutations or alterations
- Part 1B: Advanced/metastatic GI tumors (e.g., PDAC, CRC, and BTC) with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations
- Part 1C: Advanced/metastatic PDAC with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations
- Part 1D: Colorectal adenocarcinoma with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations
- Part 1E: Other advanced/metastatic non-GI, non-NSCLC solid tumors with KRAS, HRAS, NRAS, BRAF, CRAF (RAF1) mutations or alterations
Part 2 Dose Optimization and Expansion cohorts ONLY:
- Part 2A: Advanced/metastatic NSCLC with KRAS non-G12C mutations and/or BRAF mutations
- Part 2A1: Advanced/metastatic NSCLC with KRAS non-G12C mutations
- Part 2A2: Advanced/metastatic NSCLC with BRAF mutations
- Part 2A3: Advanced/metastatic NSCLC with KRAS non-G12C or BRAF mutations or alterations and active CNS metastatic disease
- Part 2A4: Advanced/metastatic NSCLC with a KRAS G12C mutation
- Part 2B1: Advanced/metastatic PDAC with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations
- Part 2B2: Advanced/metastatic CRC with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations
- Part 2B3: Advanced/metastatic BTC (adenocarcinoma) with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations
You CAN'T join if...
- Cancer that has a known MEK1/2 mutation.
- Known allergy/hypersensitivity to excipients of S241656 or to any of the registered IMPs administered in combination.
- Any contra-indication, to use of any of the combination chemotherapy or anti-EGFR therapy partners administered as part of this trial.
- Major surgery within 4 weeks of study entry or planned during study.
- Ongoing anticancer therapy.
- Ongoing radiation therapy.
- Uncontrolled or active clinically relevant bacterial, fungal, or specific viral infection requiring systemic therapy.
- Clinically significant cardiovascular disease.
- Symptomatic spinal cord compression.
- Evidence of active malignancy (other than study-specific malignancies) requiring systemic therapy within the next 2 years.
- History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
- Females who are pregnant or breastfeeding.
- Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study.
- Prior use of experimental agents that target the KRAS/BRAF/MEK/ERK pathway.
Locations
- University of California, San Francisco (UCSF)
accepting new patients
San Francisco California 94143 United States - The Angeles clinic - A cedars SINAI AFFILIATE
accepting new patients
Los Angeles California 90025 United States - USC Norris Comprehensive Cancer Center
accepting new patients
Los Angeles California 90033 United States
Lead Scientist at University of California Health
- Varun Monga (ucsf)
Dr. Varun Monga is a Board Certified Medical Oncologist who serves as an Clinical Associate Professor of Medicine in the Division of Hematology and Oncology. He joined UCSF Medical Center in 2023 and he provides patient care services limited to UCSF Sarcoma Center and Cancer Clinical Trials and Investigational Treatments Center.
Details
- Status
- accepting new patients
- Start Date
- Completion Date
- (estimated)
- Sponsor
- Institut de Recherches Internationales Servier
- ID
- NCT05786924
- Phase
- Phase 1/2 research study
- Study Type
- Interventional
- Participants
- Expecting 554 study participants
- Last Updated
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