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

• Status: Recruiting
• Trial end date: 2025-03-01
• Target enrollment: 0
• Participant gender: All

Summary

This Phase 1a/1b study will evaluate the safety, tolerability and the pharmacokinetics/pharmacodynamics (PK/PD) of KT-333 in Adult patients with Relapsed or Refractory Lymphomas, Large Granular Lymphocytic Leukemia, and Solid Tumors. The Phase 1a stage of the study will explore escalating doses of single-agent KT-333. The Phase Ib stage will consist of 4 expansion cohorts to further characterize the safety, tolerability and the pharmacokinetics/pharmacodynamics (PK/PD) of KT-333 in Peripheral T-cell Lymphoma (PTCL), Cutaneous T-Cell Lymphoma (CTCL), Large Granular Lymphocytic Leukemia (LGL-L), and solid tumors.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Kymera Therapeutics, Inc.

Criteria

Inclusion Criteria:

1. Phase 1a Only: Histologically or pathologically confirmed Lymphomas (including Hodgkin's, B-cell, T-cell, Small Lymphocytic, or NK-cell Lymphomas) with the exception of chronic lymphocytic leukemia (CLL) or solid tumors (solid tumor permitted in the MTD/RP2D confirmation portion only).

Note: Patients with indolent NHL and small lymphocytic lymphoma (SLL) are only eligible if not require immediate cytoreductive therapy or if there are no available treatments with potential benefit.

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 prior to first dose of the study drug (for lymphoma patients) or within 2 years prior to first dose of the study drug (for solid tumor patients). .

4. Phase 1a only: 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 1b only: Relapsed and/or refractory disease to at least 1 prior systemic standard of care treatments or for whom standard therapies are not available.

6. LGL-L patients only:

• Severe neutropenia < 500/mm3, or,

• Neutropenia associated with recurrent infection, or,

• Symptomatic anemia and/or,

• Transfusion-dependent anemia.

7. PTCL and solid tumors Only: Measurable disease at Screening.

8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at Screening and C1D1 (pre-dose).

9. 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. 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.

Exclusion Criteria:

1. History or suspicion of central nervous system (CNS) metastases.

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

3. 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.

4. Ongoing unstable cardiovascular function.

5. Autologous hematopoietic stem cell transplant less than 3 months prior to first dose of study drug.

6. Prior allogenic hematopoietic or bone marrow transplant.