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

Eligibility Criteria

• 1. Disease criteria:
• 1. Histologically or cytologically confirmed recurrent/advanced (unresectable) or metastatic solid tumors or histiocytic neoplasms with documented RAS or BRAF mutations.
• 2. Dose Escalation cohorts:
• * NSCLC with KRAS non-G12C mutations, including other mutations at KRAS-G12 (eg, G12V/G12D) and other oncogenic variants of KRAS mutations on G13 and Q61 amino acid residues, BRAF, or CRAF mutations.
• * Melanoma with BRAF, CRAF, or NRAS mutations.
• * Histiocytic neoplasms with BRAF or NRAS mutations.
• * Thyroid carcinoma with BRAF 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 or local standard-of-care with Sponsor approval.
• 3. Dose Expansion cohort:
• 2. Prior standard-of-care
• 1. Exhausted all available standard-of-care therapies or, in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from available standard-of-care therapy.
• 2. Patients with eligible tumors harboring BRAF V600E mutations must have received FDA approved BRAF targeted therapy, BRAF/MEK inhibitors combination, or BRAF inhibitors combination.
• 3. Evaluable or measurable disease in dose escalation and measurable disease only for dose expansion cohorts.
• 4. Adequate bone marrow and organ function.
• 5. Recovered from toxicity to prior anti-cancer therapy.
• 6. Appropriate candidate for BDTX-4933 monotherapy.
• 7. Life expectancy of \>=12 weeks in the opinion of the Investigator.
• 1. Cancer that has a known MEK1/2 mutation.
• 2. Major surgery within 4 weeks of study entry or planned during study.
• 3. Ongoing anticancer therapy.
• 4. Ongoing radiation therapy.
• 5. Uncontrolled or active clinically relevant bacterial, fungal, or specific viral infection requiring systemic therapy.
• 6. Symptomatic spinal cord compression.
• 7. Evidence of active malignancy (other than study-specific malignancies) requiring systemic therapy within the next 2 years.
• 8. History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
• 9. Females who are pregnant or breastfeeding.
• 10. Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study.
• 11. Prior use of experimental agents that target the KRAS/BRAF/MEK/ERK pathway.