A Study to Assess the Safety and Tolerability of CFT8634 in Locally Advanced or Metastatic SMARCB1-Perturbed Cancers, Including Synovial Sarcoma and SMARCB1-Null Tumors

Inclusion Criteria

• •1. Subject (and legal guardian where applicable) is (are) willing and able to provide signed informed consent (or assent, where applicable) and can follow protocol requirements
• •2. Subject has histologically or cytologically confirmed synovial sarcoma or SMARCB1-null sold tumor that is relapsed/refractory, and unresectable or metastatic; the subject must not be a candidate for available therapies that are known to confer clinical benefit
• •a. Phase 1: subject must have received ≥1 prior line of systemic anticancer therapy considered to be Standard of Care per the Investigator's judgment, in the metastatic or unresectable setting b. Phase 2: i. Arm A: subject must have received only 1-2 prior lines of systemic anticancer therapy considered to be Standard of Care per the Investigator's judgment, in the metastatic or unresectable setting ii. Arm B: subject must have received ≥1 prior line of systemic anticancer therapy considered to be Standard of Care per the Investigator's judgment, in the metastatic or unresectable setting
• •3. Subject must be:
• •* ≥18 years of age (no minimum weight),
• •* ≥16 and \<18 years old and weighs ≥50 kg,
• •* ≥12 and \<16 years of age and weighs ≥40kg,
• •* or ≥16 and \<18 years of age and weighs ≥40kg and \<50kg
• •4. Subject must be able to safely swallow capsules
• •5. Subject must have measurable disease as defined by RECIST v1.1
• •6. Subject must have Eastern Cooperative Oncology Group performance status ≤2 or Lansky performance scale (LK scale) ≥ 60
• •7. Subject must have adequate organ function, defined as:
• •1. Bone marrow function: absolute neutrophil count ≥1.0 x 109/L independent of growth factor support for ≤7 days prior to first dose of study drug for granulocyte colony-stimulating factor and ≤14 days prior to first dose of study drug for peg-filgrastim; hemoglobin ≥8 g/dL independent of transfusion support for ≤7 days prior to first dose of study drug; platelet count ≥75 x 109 /L independent of transfusion support for ≤3 days prior to first dose of study drug
• •2. Coagulation: Prothrombin time (PT)/international normalized ratio (INR) \<1.5x the upper limit of normal (ULN) and activated partial thromboplastin time (aPTT) \<1.5x ULN (unless the subject is receiving anticoagulant therapy and INR and partial PT/aPTT are within therapeutic range of intended use of anticoagulants)
• •3. Liver function: total bilirubin ≤1.5x ULN (≤3.0x ULN for subjects with Gilbert's syndrome), aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0x ULN; except for subjects who have tumor infiltration of the liver, where ALT and AST ≤5x ULN
• •4. Renal function: must have a creatinine clearance ≥60 mL/min (via Cockcroft-Gault equation, institutional standard, or measured)
• •5. Cardiac function: baseline corrected QT interval using Fredericia's formula ≤470 ms (adolescents 12-17 years of age: ≤450 ms) and a left ventricular ejection fraction ≥50% evaluated via echocardiogram or multi-gated acquisition (MUGA) scan
• •8. Availability of archival tumor tissue sample or newly obtained core/excisional biopsy of a tumor not previously irradiated
• •9. A female subject may be eligible to participate if she is not pregnant or planning a pregnancy, not breastfeeding, and following protocol mediated guidance to avoid pregnancy
• •10. A male subject must have had a prior vasectomy and agree to use a condom during the treatment period and for at least 90 days after the last dose of study treatment
• •11. A male subject must refrain from donating sperm while taking CFT8634 and for 90 days post-last dose
• •12. A female subject must refrain from donating ova while taking CFT8634 and for 180 days after discontinuation
• •13. All subjects must refrain from donating blood and blood products while receiving study drug and for 30 days post-last dose