A Study of BDTX-4933 in Patients With BRAF and Select RAS/MAPK Mutation-Positive Cancers

Key Inclusion Criteria: Disease criteria: Histologically or cytologically confirmed recurrent/advanced metastatic solid tumors or histiocytic neoplasms with documented BRAF or RAS (NRAS or KRAS) mutations. Note: Patients may have stable central nervous system (CNS) metastases. Patients with CNS gliomas or active CNS metastases or primary CNS tumors associated with progressive neurological symptoms or needing increased doses of corticosteroids to control the CNS disease are excluded from the study. Dose Escalation cohorts: Melanoma with BRAF (Class I, II, or III) or NRAS mutations. NSCLC with BRAF (Class II or III) or KRAS mutations other than G12C (ie, G12D, G12V) mutations (with Sponsor approval for KRAS mutations). Histiocytic neoplasms with BRAF (Class I, II, or III) or NRAS mutations. Thyroid carcinoma with BRAF (Class I, II, or III) mutations. Colorectal carcinoma with BRAF (Class II or III) mutations with Sponsor approval. Other solid tumors with BRAF Class I mutations after prior treatment with a BRAF/MEK inhibitor with Sponsor approval. Dose Expansion cohorts: Cohort 1: Recurrent NSCLC with BRAF Class II alterations or KRAS mutations other than G12C (ie, G12D, G12V) mutations (with Sponsor approval for KRAS mutations) without small cell lung cancer transformation with progressive disease confirmed by radiographic assessment. Cohort 2: Recurrent histiocytic or intolerant neoplasms with BRAF or NRAS alterations with progressive disease confirmed by radiographic assessment or intolerance of standard of care. Cohort 3: Recurrent NSCLC (without small cell lung cancer transformation) or melanoma with BRAF Class I mutations with progressive disease after prior standard of care therapy. Cohort 4: Recurrent melanoma with NRAS mutations with progressive disease confirmed by radiographic assessment. Received prior systemic therapy (must have received 1 but no more than 2 prior lines of therapy; patients with melanoma may have up to 3 prior lines of therapy). Evaluable or measurable disease in dose escalation and measurable disease only for dose expansion cohorts. Adequate bone marrow and organ function. Recovered from toxicity to prior anti-cancer therapy. Appropriate candidate for BDTX-4933 monotherapy. Life expectancy of >=12 weeks in the opinion of the Investigator. Key Exclusion Criteria: Cancer that has a known MEK1/2 mutation. Major surgery within 4 weeks of study entry or planned during study. Ongoing or recent anticancer therapy. Ongoing or recent radiation therapy. Uncontrolled or active clinically relevant bacterial, fungal, or specific viral infection requiring systemic therapy. 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.