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
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
Mechanism of Action
KT-253 is an MDM2 degrader
Purpose
In this study, the sponsor and investigators want to learn:
- How much of the study drug can be given with an acceptable level of side effects
- The effects of the study drug (good and bad)
- How much of the study drug is absorbed into the blood and how fast it is removed
- If research tests can be used in the future to predict who will benefit from KT-253
- How the study drug is acting on your body
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.
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.
Relapsed and/or refractory disease to at least two prior standard of care treatments or tumors for whom standard therapies are not available. Note: For patients with lymphoma, the following apply: o must be ineligible for autologous stem cell transplants (ASCT) or chimeric antigen receptor T-cells (CAR-T) therapy or o patient has refused ASCT or CAR-T therapy. Note: Prior ASCT or CAR-T therapy are not exclusionary
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