A Phase 1, Multicenter, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Intravenously Administered KT-253 in Adult Patients With High Grade Myeloid Malignancies and Acute Lymphocytic Leukemia, Lymphoma and Advanced Solid Tumors

KT253-AL-101

This Phase 1 study will evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics (PK/PD), and clinical activity of KT-253 in adult patients with relapsed or refractory (R/R) high grade myeloid malignancies, acute lymphocytic leukemia (ALL), R/R lymphoma, and R/R solid tumors. The study will identify the pharmacologically optimal dose(s) of KT-253 as the recommended Phase 2 dose (RP2D), based on all safety, PK, PD, and efficacy data.

2023-05-15

2024-11-01

2025-11-01

Recruiting

Early phase I

70

Inclusion Criteria: 1. All Participants: * Eastern Cooperative Oncology Group performance status: 0-2. * Resolved acute effects of any prior therapy except for alopecia to baseline severity or Grade ≤1 NCI CTCAE and Grade ≤2 neuropathy * Adequate organ function at screening 2. 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. 3. Advanced high grade myeloid malignancies, and Acute Lymphocytic Leukemia (Arm B) ONLY * Primary diagnosis of AML, ALL, High/Very High-risk MDS, MDS/MPN. Must be relapsed/refractory to standard therapies. 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. * 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. * Known presence of p53 mutation in tumor tissue 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). 3. 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 (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.

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2024-04-23