Safety and Clinical Activity of KT-253 in Adult Patients with High Grade Myeloid Malignancies, Acute Lymphocytic Leukemia, Lymphoma, Solid Tumors

Exclusion Criteria

• •1. All Participants:
• •* Ongoing unstable cardiovascular function.
• •* Major surgery requiring general anesthesia within 4 weeks prior to first dose of study drug.
• •* History of or active concurrent malignancy unless disease-free for ≥ 2 years.
• •* Known presence of p53 mutations in tumor tissue or blood, which are known to completely inactivate p53 transcriptional activity
• •2. Solid Tumors and Lymphoma (Arm A) ONLY
• •* Known active uncontrolled or symptomatic central nervous system (CNS) metastases.
• •* Autologous or allogenic hematopoietic stem cell transplant (HSCT) within six months prior to first dose of study drug or participant has progressed within six months from the day of stem cell infusion (for lymphoma participants only).
• •* Exposures to anticancer therapy or investigational therapy within 2 weeks or 5 half-lives whichever is longer prior to the first dose of study drug.
• •* Received immunotherapy/biologic treatment or investigational therapy within 4 weeks prior to first dose of KT-253, including tumor vaccines and checkpoint inhibitors.
• •3. Advanced high grade myeloid malignancies, and Acute Lymphocytic Leukemia (Arm B) ONLY
• •* Active CNS leukemia. Participants with symptoms suggestive of CNS disease will require a lumbar puncture to rule out CNS disease.
• •* Prior chemotherapy/radiation (including craniospinal radiation) within 2 weeks prior to the first dose of study drug.
• •* Received allogeneic hematopoietic cell transplantation (HCT) \<12 weeks prior to first dose or donor lymphocyte infusion (DLI) without conditioning \<4 weeks prior to first dose.
• •* Received autologous stem cell transplant (ASCT) \< 4 weeks prior to first dose or the patient has not recovered from transplant associated toxicities to ≤ grade 1 prior to the first dose of study drug.
• •* Received chimeric antigen receptor therapy or other modified T cell therapy \<3 weeks prior to the first dose.
• •* Patients with signs or symptoms of Grade ≥ 2 acute or chronic graft versus host disease (GVHD) within 2 weeks of enrollment.