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

NCT05225584 | Completed Phase 1 FDA Drug

• 1 other identifier: KT333-TL-101
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 13

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 Lymphocytic Leukemia (LGL-L), T-cell prolymphocytic leukemia (T-PLL), 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), LGL-L, and solid tumors.

Conditions

Non Hodgkin Lymphoma (NHL); Peripheral T-cell Lymphoma (PTCL); Cutaneous T-Cell Lymphoma (CTCL); Large Granular Lymphocytic Leukemia (LGL-L); T-cell Prolymphocytic Leukemia (T-PLL); Solid Tumors

Outcome Measures

Primary Outcomes (5)

• Safety

  Incidence and severity of adverse events as assessed by CTCAE v5.0 Phase 1a/1b

  Safety will be assessed from the time ICF signature through 30 days post dose or prior to start of a new anticancer therapy

• Safety

  Incidence and severity of clinical laboratory abnormalities in Serum Chemistry, Hematology, Coagulation Parameters and urinalysis tests as assessed by CTCAE v5.0 Phase 1a/1b

  Safety will be assessed from the time ICF signature through 30 days post dose or prior to start of a new anticancer therapy

• Safety

  Changes in the ECG parameters, including heart rate and measures PR, QRS, QT, and QTc intervals as assessed by CTCAE v5.0 Phase 1a/1b

  Safety will be assessed from the time ICF signature through 30 days post dose or prior to start of a new anticancer therapy

• Maximum Tolerated Dose (MTD)

  To establish the Maximum Tolerated Dose (MTD) Phase 1a

  Within the first 28 days of treatment

• Dose Limiting Toxicities (DLTs)

  Number of Participants with protocol specified Dose Limiting Toxicities (DLTs) Phase 1a

  Within the first 28days of treatment

Secondary Outcomes (11)

• Area under the plasma concentration versus time curve for KT-333

  Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 28days)

• Maximum Plasma Concentration of KT-333 (Cmax)

  Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 28days)

• Time of maximum plasma concentration of KT-333 (Tmax)

  Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 28days)

• Half-life of KT-333 if data permits (T1/2)

  Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 28days)

• Amount of KT-333 dose excreted in urine from time zero to last collected time point (Ae0-t)

  Urine samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 28days)

Study Arms (8)

Phase 1a Dose Escalation Lymphomas

EXPERIMENTAL

KT-333 dosed IV weekly in 28 day cycles

Drug: KT-333

Phase 1a Dose Escalation Solid Tumors

EXPERIMENTAL

KT-333 dosed IV weekly in 28 day cycles

Drug: KT-333

Phase 1b Dose Expansion PTCL

EXPERIMENTAL

KT-333 dosed IV weekly in 28 day cycles

Drug: KT-333

Phase 1b Dose Expansion CTCL

EXPERIMENTAL

KT-333 dosed IV weekly in 28 day cycles

Drug: KT-333

Phase 1b Dose Expansion LGL-L

EXPERIMENTAL

KT-333 dosed IV weekly in 28 day cycles

Drug: KT-333

Phase 1b Dose Expansion Solid Tumor

EXPERIMENTAL

KT-333 dosed IV weekly in 28 day cycles

Drug: KT-333

Phase 1a Dose Escalation LGL-L

EXPERIMENTAL

KT-333 dosed IV weekly in 28 day cycles

Drug: KT-333

Phase 1a Dose Escalation T-PLL

EXPERIMENTAL

KT-333 dosed IV weekly in 28 day cycles

Drug: KT-333

Interventions

KT-333 DRUG

KT-333 will be supplied as 10mg/mL concentration frozen solution to be administered intravenously per the protocol defined frequency and dose level.

Phase 1a Dose Escalation LGL-L; Phase 1a Dose Escalation Lymphomas; Phase 1a Dose Escalation Solid Tumors; Phase 1a Dose Escalation T-PLL; Phase 1b Dose Expansion CTCL; Phase 1b Dose Expansion LGL-L; Phase 1b Dose Expansion PTCL; Phase 1b Dose Expansion Solid Tumor

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kymera Therapeutics, Inc.: lead

Study Sites (13)

UC Irvine Health-Chao Family Comprehensive Cancer Center

Orange, California, 92868-3201, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40207, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Hackensack University Medical Center, John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine

The Bronx, New York, 10467, United States

Location

The Christ Hospital Cancer Center

Cincinnati, Ohio, 45219, United States

Location

Ohio State University Wexner Medical Center

Columbus, Ohio, 43210-1240, United States

Location

Abramson Cancer Center of the University of Pennsylvania Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Virginia, Emily Couric Cancer Center

Charlottesville, Virginia, 22903, United States

Location

University of WA/Seattle Cancer Care Alliance

Seattle, Washington, 98195, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Leukemia, Large Granular Lymphocytic; Leukemia, Prolymphocytic, T-Cell

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, T-Cell; Leukemia, T-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Leukemia, Prolymphocytic

Study Officials

• Ashwin Gollerkeri, MD

  Kymera Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2021
• First Posted: February 4, 2022
• Study Start: May 19, 2022
• Primary Completion: March 3, 2025
• Study Completion: March 3, 2025
• Last Updated: March 19, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)