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

Trial status: Authorised 1. Dose Escalation: PK parameters of S241656 and its metabolite S243796, including but not limited to Cmax, tmax, AUC, and t½, 2. Dose Escalation: Objective response Disease Control Clinical Benefit Duration of Response Time to response Progression free survival Overall survival, 3. Dose Escalation: Clinical efficacy parameters Safety and tolerability parameters PK including: Exposure-toxicity relationship, 4. Dose Expansion: Clinical Efficacy Parameters Safety and Tolerability Parameters PK & PD parameters, 5. Dose Expansion: Disease Control Clinical Benefit Duration of Response Time to Response Progression free survival Overall Survival, 6. Dose Expansion: PK parameters of S241656 and its metabolite S243796, but not limited to Cmax, tmax, AUC, and t½ Dose Escalation: Incidence of dose-limiting toxicities occurring within the first 28-day cycle Number of Adverse Events and Serious Adverse Events Dose Expansion: Objective response

1. Dose Escalation: PK parameters of S241656 and its metabolite S243796, including but not limited to Cmax, tmax, AUC, and t½, 2. Dose Escalation: Objective response Disease Control Clinical Benefit Duration of Response Time to response Progression free survival Overall survival, 3. Dose Escalation: Clinical efficacy parameters Safety and tolerability parameters PK including: Exposure-toxicity relationship, 4. Dose Expansion: Clinical Efficacy Parameters Safety and Tolerability Parameters PK & PD parameters, 5. Dose Expansion: Disease Control Clinical Benefit Duration of Response Time to Response Progression free survival Overall Survival, 6. Dose Expansion: PK parameters of S241656 and its metabolite S243796, but not limited to Cmax, tmax, AUC, and t½

Age group: 65+ years, 18-64 years Gender: Female, Male Target enrollment: 75 participants