Study on the Safety and Effectiveness of CFT1946 Alone and in Combination for BRAF V600 Mutant Solid Tumors

Inclusion Criteria

• Must be willing and able to provide informed consent and follow study requirements.
• Must be 18 years or older.
• Must have a performance status score of 0 or 1, indicating full activity or some restriction in strenuous activities.
• Must have a confirmed BRAF V600 mutation from tumor tissue or a blood test.
• Must have received at least one prior treatment for advanced or metastatic disease, with disease progression after the last treatment. Specific prior treatments depend on the type of cancer:
  • Melanoma or NSCLC: Must have received a BRAF inhibitor and an immune checkpoint inhibitor.
  • CRC: Must have received up to 4 prior treatments, including chemotherapy and a BRAF inhibitor with an EGFR antibody. MSI-H or dMMR CRC must have had prior immunotherapy.
  • ATC: Must have received standard therapy, including a BRAF inhibitor if beneficial.
  • Other BRAF V600 mutant solid tumors: Must have received standard therapy, including a BRAF inhibitor if beneficial.
• Must have measurable disease according to standard criteria.
• Must have adequate bone marrow, liver, kidney, and heart function.
• Women must not be pregnant or breastfeeding and must agree to use contraception if of childbearing potential.
• Men must agree to use contraception and not donate sperm.
• Must be able to swallow tablets or pills.

Exclusion Criteria

• Recent major surgery within 21 days before the first dose (minor surgery is allowed).
• Active or untreated brain tumors, unless stable and not requiring steroids.
• Other progressing cancers requiring treatment in the past 3 years, except those treated with curative intent.
• Recent history of blood clots or strokes within 6 months.
• Significant heart problems.
• Uncontrolled diabetes (for those receiving CFT1946 + trametinib).
• Eye conditions like retinal vein occlusion (for those receiving CFT1946 + trametinib).
• Recent live vaccines within 28 days before the first dose.
• History of lung inflammation or interstitial lung disease.
• History of eye inflammation (uveitis).
• Significant digestive system issues.
• Known HIV infection (with some exceptions).
• History of hepatitis B or active hepatitis C infection.
• Use of certain strong medications or supplements that affect drug metabolism.
• Ongoing side effects from previous cancer treatments, except hair loss and thyroid issues.
• Recent blood cell growth factors or transfusions within 7 days before the first dose.
• Pregnant or breastfeeding, or planning to conceive or father a child during the study.