Solid Tumor
Conditions
Interventions
S241656 is administered orally once daily or twice daily.
Sponsors
Kabir Mody
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - 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
Exclusion criteria
Exclusion criteria: - 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - Dose Escalation: Incidence of dose-limiting toxicities (DLTs) - Dose Escalation: Number of Adverse Events (AEs) and Serious Adverse Events (SAEs) - Dose Optimization/Expansion: Objective response (OR) | — |
Countries
Australia, China, Denmark, France, Hong Kong, Italy, Japan, Spain, United Kingdom, United States
Contacts
Public ContactMasato Fukui
Medpace Japan KK
Outcome results
None listed