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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
554
RAF inhibitor targeting all classes of oncogenic BRAF alterations (Classes I, II, and III) and constitutively active CRAF, KRAS or NRAS mutations
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
Banner Health- MD Anderson Cancer Center
Gilbert, Arizona, United States
RECRUITINGUniversity of Colorado - Aurora Cancer Center
Aurora, Colorado, United States
NOT_YET_RECRUITINGGeorgetown University Lombardi Cancer Center
Washington D.C., District of Columbia, United States
NOT_YET_RECRUITINGDana-Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGSouth Texas Accelerated Research Therapeutics (START) Midwest
Grand Rapids, Michigan, United States
RECRUITINGMasonic Cancer Center University of Minnesota
Minneapolis, Minnesota, United States
RECRUITINGWashington University
St Louis, Missouri, United States
RECRUITINGMemorial Sloan Kettering Cancer Center
New York, New York, United States
RECRUITINGNEXT Virginia
Fairfax, Virginia, United States
RECRUITINGFred Hutchinson Cancer Research Center
Seattle, Washington, United States
RECRUITINGDose 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
Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department
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