Status:
COMPLETED
Safety, PK, PD, Clinical Activity of KT-333 in Adult Patients With Refractory Lymphoma, Large Granular Lymphocytic Leukemia, Solid Tumors
Lead Sponsor:
Kymera Therapeutics, Inc.
Conditions:
Non Hodgkin Lymphoma (NHL)
Peripheral T-cell Lymphoma (PTCL)
Eligibility:
All Genders
18+ years
Phase:
PHASE1
Brief 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 (R/R) Lymphomas, Large Granular ...
Detailed Description
This is an open-label Phase 1a (dose escalation)/1b (dose expansion) first-in-human study of KT-333 in adult patients. Patients with relapsed/refractory (R/R) lymphomas, LGL-L, T-PLL, and solid tumors...
Eligibility Criteria
Inclusion
- Phase 1a Only: Cytologically or pathologically confirmed Lymphomas (including Hodgkin's, B-cell, T-cell, Small Lymphocytic, or Natural-Killer (NK)-cell Lymphomas and LGL-L), T-PLL and solid tumors with the exception of chronic lymphocytic leukemia (CLL) Note: Patients with indolent non-Hodgkin's lymphoma (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.
- 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.
- 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).
- 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.
- 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.
- 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.
- 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).
- 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
- PTCL and solid tumors Only: Measurable disease at Screening. Solid tumor patients with non-measurable disease are allowed in Phase1a
- T-PLL: Measurable disease per Lugano and/or atypical T lymphocytes quantifiable by flow cytometry or morphology in the peripheral blood or bone marrow.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at Screening and C1D1 (pre-dose).
- 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
- Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth.
- Note: Patients with solid tumors are eligible if their CNS metastases or cord compression have been treated (e.g., radiotherapy, stereotactic surgery) and they are clinically stable, off steroids for at least 4 weeks before first dose of study drug and have no evidence of progression at time of study enrollment.
- Note: Patients with lymphomas are eligible if their CNS metastases or cord compression have been treated effectively (i.e. achieved CR) and there is no clinical or radiographic evidence of active lymphoma.
- Diagnosis of Chronic Lymphocytic Leukemia (CLL).
- History of or active concurrent malignancy other than lymphoma or solid tumors unless the patient has been disease-free for ≥ 2 years.
- 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.
- Ongoing unstable cardiovascular function.
- Autologous hematopoietic stem cell transplant less than 3 months prior to first dose of study drug.
- Prior allogenic hematopoietic or bone marrow transplant.
Key Trial Info
Start Date :
May 19 2022
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 3 2025
Estimated Enrollment :
56 Patients enrolled
Trial Details
Trial ID
NCT05225584
Start Date
May 19 2022
End Date
March 3 2025
Last Update
March 19 2025
Active Locations (13)
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1
UC Irvine Health-Chao Family Comprehensive Cancer Center
Orange, California, United States, 92868-3201
2
Norton Cancer Institute
Louisville, Kentucky, United States, 40207
3
Henry Ford Hospital
Detroit, Michigan, United States, 48202
4
Hackensack University Medical Center, John Theurer Cancer Center
Hackensack, New Jersey, United States, 07601