A Study to Characterize the Safety, Tolerability, and Preliminary Efficacy of CFT1946 as Monotherapy and Combination Therapy in Subjects With BRAF V600 Mutant Solid Tumors

Exclusion Criteria

• •1. Subject has had major surgery within 21 days prior to the planned first dose. Minor surgery is permitted within 21 days prior to enrollment
• •2. Subject with CNS involvement (primary tumor or metastatic disease), except if clinically stable, have no evidence of new or enlarging brain metastases and are on stable or tapering doses of steroids for at least 7 days prior to first dose. Subjects with untreated brain metastases may be eligible to enter without prior radiation therapy.
• •3. Subject with known malignancy other than trial indication that is progressing or has required treatment within the past 3 years, except for conditions that have undergone potentially curative therapy
• •4. Subject with history of thromboembolic or cerebrovascular events ≤6 months as defined in the protocol
• •5. Subject with impaired cardiac function or clinically significant cardiac disease, as defined in the protocol
• •6. Subject with history of uncontrolled diabetes mellitus (only for subjects who will receive CFT1946 + trametinib)
• •7. Subject with history or current evidence of retinal vein occlusion (RVO), chorioretinopathy, or current risk factors for RVO (only for subjects who will receive CFT1946 + trametinib)
• •8. Subject has received live, attenuated vaccine within 28 days prior to first dose administration
• •9. Subject has history of pneumonitis or interstitial lung disease
• •10. Subject has history of uveitis
• •11. Subject has clinically significant gastrointestinal abnormalities.
• •12. Subject has known human immunodeficiency virus (HIV) infection (with exceptions)
• •13. Subject has history of or known HBV or active HCV infection
• •14. Subject has concurrent administration of strong CYP3A4/5 inhibitors and inducers, including any herbal medications/supplements
• •15. Subject has presence of Grade ≥2 toxicity due to prior cancer therapy, excepting alopecia and hypothyroidism requiring thyroid replacement therapy
• •16. Subject has initiation or receipt of the following ≤7 days prior to first dose administration: Hematopoietic colony-stimulating growth factors, transfusion of packed red blood cells (pRBC), and transfusion of platelets
• •17. Subject is pregnant, breastfeeding, or expecting to conceive or father children any time during the study