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

Inclusion Criteria: All Patients: Eastern Cooperative Oncology Group performance status: 0-2. Resolved acute effects of any prior therapy to baseline severity or Grade ≤1 NCI CTCAE Adequate organ and bone marrow function in the absence of growth factors Solid Tumors and Lymphoma (Arm A) ONLY Histologically or pathologically confirmed solid tumor or lymphoma. Relapsed and/or refractory (R/R) disease to at least two prior standard-of-care treatments or tumors for whom standard therapies are not available. Advanced high grade myeloid malignancies, and Acute Lymphocytic Leukemia (Arm B) ONLY Primary diagnosis of AML, ALL, Relapsed/progressed high-risk Myelodysplastic Syndromes (MDS), Myelodysplastic/myeloproliferative neoplasms (MDS/MPN). Must be relapsed/refractory to standard therapies. At least 4 weeks since radiotherapy prior to the first dose of study drug. Exclusion Criteria: All Participants: Ongoing unstable cardiovascular function. Major surgery within 4 weeks of study entry. History of or active concurrent malignancy unless disease-free for ≥ 2 years. Exposures to anticancer therapy within 2 weeks or 5 half-lives whichever is shorter; or 4 weeks from any biologics/immunotherapies or any investigational therapy prior to the first dose of study drug. Solid Tumors and Lymphoma (Arm A) ONLY Known active uncontrolled or symptomatic central nervous system (CNS) metastases. Autologous 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). Prior allogeneic hematopoietic stem cell transplant. Advanced high grade myeloid malignancies, and ALL (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 within ≤ 2 weeks of first dose of study drug Known systemic vasculitides (e.g., Wegener's granulomatosis, polyarteritis nodosa, systemic lupus erythematosus). Participant is within 3 months post allogenic hematopoietic stem cell transplant or within 30 days post autologous stem cell transplant, and the participant has not recovered from transplant-associated toxicities. Patients with active or chronic graft versus host disease (GVHD) or on treatment for GVHD.