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

Inclusion Criteria:

1. Phase 1a Only: Cytologically or pathologically confirmed Lymphomas (includingHodgkin's, B-cell, T-cell, Small Lymphocytic, or Natural-Killer (NK)-cell Lymphomasand LGL-L), T-PLL and solid tumors with the exception of chronic lymphocyticleukemia (CLL) Note: Patients with indolent non-Hodgkin's lymphoma (NHL) and smalllymphocytic lymphoma (SLL) are only eligible if not require immediate cytoreductivetherapy or if there are no available treatments with potential benefit.

2. Phase 1b Only: Histologically or pathologically confirmed PTCL, CTCL, LGL-L [T-cellLGL-L or Chronic Lymphoproliferative Disorder of NK-cells (CLPD-NK)], or solidtumors.

3. Fresh or archival formalin fixed paraffin embedded (FFPE) tumor tissue or 15 slidespreferably collected within 6 months or 2 years prior to first dose of the studydrug (for lymphoma and solid tumor patients respectively).

4. Phase 1a only: Lymphoma and Solid Tumor: Relapsed and/or refractory disease to atleast 2 prior systemic standard of care treatments or for whom standard therapiesare not available.

5. Phase 1a: LGL-L/T-PLL only: Relapsed and/or refractory disease to at least 1 priorsystemic standard of care treatment or for whom standard therapies are notavailable.

6. Phase 1b only: All disease types: Relapsed and/or refractory disease to at least 1prior systemic standard of care treatments or for whom standard therapies are notavailable.

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 platelettransfusion 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 +TCRis required;

• NK LGL is also permitted, provided there is a clonal NK-cell population notedwith>500 cells/mm3

9. PTCL and solid tumors Only: Measurable disease at Screening. Solid tumor patientswith non-measurable disease are allowed in Phase1a

10. T-PLL: Measurable disease per Lugano and/or atypical T lymphocytes quantifiable byflow cytometry or morphology in the peripheral blood or bone marrow.

11. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at Screening andC1D1 (pre-dose).

12. Adequate bone marrow function at Screening and C1D1 (pre-dose) for all patientsexcept 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 effectivecontraceptive methods for the duration of study treatment and 6 months after thelast dose of KT333.

Exclusion Criteria:

1. Known active uncontrolled or symptomatic central nervous system (CNS) metastases,carcinomatous meningitis, or leptomeningeal disease as indicated by clinicalsymptoms, cerebral edema, and/or progressive growth. Note: Patients with solid tumors are eligible if their CNS metastases or cordcompression have been treated (e.g., radiotherapy, stereotactic surgery) and theyare clinically stable, off steroids for at least 4 weeks before first dose of studydrug and have no evidence of progression at time of study enrollment. Note: Patients with lymphomas are eligible if their CNS metastases or cordcompression have been treated effectively (i.e. achieved CR) and there is noclinical or radiographic evidence of active lymphoma.

2. Diagnosis of Chronic Lymphocytic Leukemia (CLL).

3. History of or active concurrent malignancy other than lymphoma or solid tumorsunless the patient has been disease-free for ≥ 2 years.

4. Patient has not recovered from any clinically significant adverse events (AEs) ofprevious treatments to pretreatment baseline or Grade 1 prior to first dose of studydrug.

5. Ongoing unstable cardiovascular function.

6. Autologous hematopoietic stem cell transplant less than 3 months prior to first doseof study drug.

7. Prior allogenic hematopoietic or bone marrow transplant.