Safety, PK, PD, Clinical Activity of KT-333 in Adult Patients With Refractory Lymphoma, Large Granular Lymphocytic Leukemia, Solid Tumors

Inclusion Criteria

• •2. Phase 1b Only: Histologically or pathologically confirmed PTCL, CTCL, LGL-L \[T-cell LGL-L or Chronic Lymphoproliferative Disorder of NK-cells (CLPD-NK)\], or solid tumors.
• •3. Fresh or archival formalin fixed paraffin embedded (FFPE) tumor tissue or 15 slides preferably collected within 6 months or 2 years prior to first dose of the study drug (for lymphoma and solid tumor patients respectively).
• •4. Phase 1a only: Lymphoma and Solid Tumor: Relapsed and/or refractory disease to at least 2 prior systemic standard of care treatments or for whom standard therapies are not available.
• •5. Phase 1a: LGL-L/T-PLL only: Relapsed and/or refractory disease to at least 1 prior systemic standard of care treatment or for whom standard therapies are not available.
• •6. Phase 1b only: All disease types: Relapsed and/or refractory disease to at least 1 prior systemic standard of care treatments or for whom standard therapies are not available.
• •7. LGL-L patients only (hematology specific criteria):
• •* One of the following:
• •* Severe neutropenia \< 500/mm3, or,
• •* Symptomatic anemia and/or,
• •* Transfusion-dependent anemia.
• •* ANC ≥ 200/μL at Screening and C1D1 (pre dose)
• •* Platelet count ≥ 100,000/μL (assessed ≥ 7 days following last platelet transfusion in patients with thrombocytopenia requiring platelets).
• •8. LGL-L Patients Only (baseline disease characteristics):
• •* CD3+CD8+ cell population \>650/mm3;
• •* CD3+CD8+CD57+ population \>500/mm3;
• •* Presence of a clonal T-cell receptor (within 1 month of diagnosis);
• •* Note: patients with T-LGLL may be included with PI approval even if CD3+CD8+ cell population is\<650/mm3 or CD3+CD8+CD57+ population is \<500/mm3, though +TCR is required;
• •* NK LGL is also permitted, provided there is a clonal NK-cell population noted with\>500 cells/mm3
• •9. PTCL and solid tumors Only: Measurable disease at Screening. Solid tumor patients with non-measurable disease are allowed in Phase1a
• •10. T-PLL: Measurable disease per Lugano and/or atypical T lymphocytes quantifiable by flow cytometry or morphology in the peripheral blood or bone marrow.
• •11. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at Screening and C1D1 (pre-dose).
• •12. Adequate bone marrow function at Screening and C1D1 (pre-dose) for all patients except those with LGL-L Adequate liver/kidney organ function at Screening and C1D1 (pre-dose) for all patients.
• •13. Women of childbearing potential (WOCBP) must agree to use highly effective contraceptive methods for the duration of study treatment and 6 months after the last dose of KT333.
• •2. Diagnosis of Chronic Lymphocytic Leukemia (CLL).
• •3. History of or active concurrent malignancy other than lymphoma or solid tumors unless the patient has been disease-free for ≥ 2 years.
• •4. Patient has not recovered from any clinically significant adverse events (AEs) of previous treatments to pretreatment baseline or Grade 1 prior to first dose of study drug.
• •5. Ongoing unstable cardiovascular function.
• •6. Autologous hematopoietic stem cell transplant less than 3 months prior to first dose of study drug.
• •7. Prior allogenic hematopoietic or bone marrow transplant.