Safety and Clinical Activity of KT-253 in Adult Patients With High Grade Myeloid Malignancies, Acute Lymphocytic Leukemia, Lymphoma, Solid Tumors

April 22, 2024 updated by: Kymera Therapeutics, Inc.

A Phase 1, Multicenter, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of Intravenously Administered KT-253 in Adult Patients With High Grade Myeloid Malignancies and Acute Lymphocytic Leukemia, Lymphoma and Advanced Solid Tumors

This Phase 1 study will evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics (PK/PD), and clinical activity of KT-253 in adult patients with relapsed or refractory (R/R) high grade myeloid malignancies, acute lymphocytic leukemia (ALL), R/R lymphoma, and R/R solid tumors. The study will identify the pharmacologically optimal dose(s) of KT-253 as the recommended Phase 2 dose (RP2D), based on all safety, PK, PD, and efficacy data.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is an open-label Phase 1 (dose escalation) first-in-human study (FIH) of KT-253 in adult patients. This study will be initiated in patients with lymphomas, and solid tumors and then subsequently in patients with advanced high grade myeloid malignancies and ALL. Therefore, the study is comprised of two arms to characterize the safety and tolerability of ascending doses of KT-253 in each arm. Arm A will consist of patients with lymphomas and advanced solid tumors and Arm B will consist of patients with high grade myeloid malignancies and ALL.

Study Type

Interventional

Enrollment (Estimated)

70

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85258
        • Recruiting
        • HonorHealth Research Institute
        • Contact:
    • California
      • Sacramento, California, United States, 95817
        • Recruiting
        • University of California, Davis Comprehensive Cancer Center
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Health System
        • Contact:
    • New York
      • Bronx, New York, United States, 10467
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • OU Health Stephenson Cancer Center
        • Contact:
    • Texas
      • Dallas, Texas, United States, 75390
      • Dallas, Texas, United States, 75230
        • Recruiting
        • Mary Crowley Cancer Research
        • Contact:
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
        • Contact:
    • Virginia
      • Fairfax, Virginia, United States, 22031

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. All Participants:

    • Eastern Cooperative Oncology Group performance status: 0-2.
    • Resolved acute effects of any prior therapy except for alopecia to baseline severity or Grade ≤1 NCI CTCAE and Grade ≤2 neuropathy
    • Adequate organ function at screening

  2. Solid Tumors and Lymphoma (Arm A) ONLY

    • Histologically or pathologically confirmed solid tumor or lymphoma.
    • Relapsed and/or refractory (R/R) disease to at least two prior standard-of-care treatments or tumors for whom standard therapies are not available.

  3. Advanced high grade myeloid malignancies, and Acute Lymphocytic Leukemia (Arm B) ONLY

    • Primary diagnosis of AML, ALL, High/Very High-risk MDS, MDS/MPN. Must be relapsed/refractory to standard therapies.

Exclusion Criteria:

  1. All Participants:

    • Ongoing unstable cardiovascular function.
    • Major surgery requiring general anesthesia within 4 weeks prior to first dose of study drug.
    • History of or active concurrent malignancy unless disease-free for ≥ 2 years.
    • Exposures to anticancer therapy within 2 weeks or 5 half-lives whichever is shorter; or 4 weeks from any biologics/immunotherapies or any investigational therapy prior to the first dose of study drug.
    • Known presence of p53 mutation in tumor tissue

  2. Solid Tumors and Lymphoma (Arm A) ONLY

    • Known active uncontrolled or symptomatic central nervous system (CNS) metastases.
    • Autologous or allogenic hematopoietic stem cell transplant (HSCT) within six months prior to first dose of study drug or participant has progressed within six months from the day of stem cell infusion (for lymphoma participants only).

  3. Advanced high grade myeloid malignancies, and ALL (Arm B) ONLY

    • Active CNS leukemia. Participants with symptoms suggestive of CNS disease will require a lumbar puncture to rule out CNS disease.
    • Prior chemotherapy/radiation (including craniospinal radiation) within 2 weeks prior to the first dose of study drug.
    • Received allogeneic hematopoietic cell transplantation (HCT) <12 weeks prior to first dose or donor lymphocyte infusion (DLI) without conditioning <4 weeks prior to first dose.
    • Received autologous stem cell transplant (ASCT) < 4 weeks prior to first dose or the patient has not recovered from transplant associated toxicities to ≤ grade 1 prior to the first dose of study drug.
    • Received chimeric antigen receptor therapy or other modified T cell therapy <3 weeks prior to the first dose.
    • Patients with signs or symptoms of Grade ≥ 2 acute or chronic graft versus host disease (GVHD) within 2 weeks of enrollment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1 Dose Escalation Arm A in patients with R/R Solid Tumors and Lymphomas
KT-253 dosed intravenous (IV) once every three weeks in 21-day cycles
Drug: KT-253
KT-253 will be administered intravenously per the defined protocol frequency and dose level.
Experimental: Phase 1 Dose Escalation Arm B in patients with R/R High Grade Myeloid Malignancies and ALL
KT-253 dosed IV once every three weeks in 21-day cycles
Drug: KT-253
KT-253 will be administered intravenously per the defined protocol frequency and dose level.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and severity of adverse events
Time Frame: From the time of signing ICF through 30 days after last dose of study drug or prior to start of a new anticancer therapy
Adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0
From the time of signing ICF through 30 days after last dose of study drug or prior to start of a new anticancer therapy
Maximum Tolerated Dose (MTD) and recommended Phase 2 dose (RP2D) in Patients
Time Frame: From the time of the first dose of study drug through 30 days after the last dose of study drug or prior to start of a new anticancer therapy
MTD and RP2D will be determined in patients with R/R high grade myeloid malignancies, ALL, and separately, in patients with lymphomas and advanced solid tumors
From the time of the first dose of study drug through 30 days after the last dose of study drug or prior to start of a new anticancer therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the Plasma Concentration versus Time Curve (AUC) of KT-253
Time Frame: Blood samples for PK analysis collected up to Day15 during cycle 1 and cycle 2 (each cycle is 21 days)
To determine the AUC from plasma concentrations in patients
Blood samples for PK analysis collected up to Day15 during cycle 1 and cycle 2 (each cycle is 21 days)
Maximum Plasma Concentration of KT-253 (Cmax)
Time Frame: Blood samples for PK analysis collected up to Day15 during cycle 1 and cycle 2 (each cycle is 21 days)
To determine the Cmax from plasma concentrations in patients
Blood samples for PK analysis collected up to Day15 during cycle 1 and cycle 2 (each cycle is 21 days)
Time to maximum plasma concentration of KT-253 (Tmax)
Time Frame: Blood samples for PK analysis collected up to Day15 during cycle 1 and cycle 2 (each cycle is 21 days)
To determine the Tmax from plasma concentrations in patients
Blood samples for PK analysis collected up to Day15 during cycle 1 and cycle 2 (each cycle is 21 days)
Evidence of Clinical activity of KT-253 in ALL patients
Time Frame: From the time of the first dose of study drug through 30 days after the last dose of study drug or until disease recurrence or death, whichever occurs first, about 18 months
Hematological remission rate defined as CR and CRh per NCCN guidelines
From the time of the first dose of study drug through 30 days after the last dose of study drug or until disease recurrence or death, whichever occurs first, about 18 months
Evidence of Clinical activity of KT-253 in MDS/ Myeloproliferative Neoplasms (MPN) patients
Time Frame: From the time of the first dose of study drug through 30 days after the last dose of study drug or until disease recurrence or death, whichever occurs first, about 18 months
Percentage of patients with CR, PR, and Marrow Response per MDS/MPN IWG
From the time of the first dose of study drug through 30 days after the last dose of study drug or until disease recurrence or death, whichever occurs first, about 18 months
Evidence of Clinical activity of KT-253 in R/R Lymphoma patients
Time Frame: From Baseline scan until first documented progression or death from any cause, whichever comes first , about 18 months
Overall Response Rate (ORR) based on Investigator's assessment as per Lugano criteria 2014 for Lymphomas
From Baseline scan until first documented progression or death from any cause, whichever comes first , about 18 months
Evidence of Clinical activity of KT-253 in R/R Solid Tumor patients
Time Frame: From Baseline scan until first documented progression or death from any cause, whichever comes first, about 18 months
Overall Response Rate (ORR) defined as percentage of patients with Complete Response or Partial Response per RECIST 1.1
From Baseline scan until first documented progression or death from any cause, whichever comes first, about 18 months
Evidence of Clinical activity of KT-253 in AML patients
Time Frame: From the time of the first dose of study drug through 30 days after the last dose of study drug or until disease recurrence or death, whichever occurs first, about 18 months
Percentage of patients with Morphologic leukemia free state (MLFS), complete remission (CR), CR with partial hematologic recovery (CRh) according to the European LeukemiaNet (ELN) response criteria.
From the time of the first dose of study drug through 30 days after the last dose of study drug or until disease recurrence or death, whichever occurs first, about 18 months
Evidence of Clinical activity of KT-253 in High/Very High-Risk Myelodysplastic syndromes (MDS) patients
Time Frame: From the time of the first dose of study drug through 30 days after the last dose of study drug or until disease recurrence or death, whichever occurs first, about 18 months
CR or CR equivalent, partial remission (PR),CR with limited count recovery, CRh, and hematologic improvement (HI) per revised International Working Group (IWG) criteria
From the time of the first dose of study drug through 30 days after the last dose of study drug or until disease recurrence or death, whichever occurs first, about 18 months
Duration of Response (DoR) in Patients Treated with KT-253
Time Frame: From date of first of response to the date of documented first progression or death whichever comes first, about 18 months
Duration of Response (DoR) in R/R high grade myeloid malignancies and ALL, R/R lymphoma and R/R solid tumor patients treated with KT-253
From date of first of response to the date of documented first progression or death whichever comes first, about 18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kymera Therapeutics, Inc.

Investigators

  • Study Director: Ashwin Gollerkeri, MD, Kymera Therapeutics, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 15, 2023

Primary Completion (Estimated)

November 1, 2024

Study Completion (Estimated)

November 1, 2025

Study Registration Dates

First Submitted

February 10, 2023

First Submitted That Met QC Criteria

March 16, 2023

First Posted (Actual)

March 20, 2023

Study Record Updates

Last Update Posted (Actual)

April 23, 2024

Last Update Submitted That Met QC Criteria

April 22, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KT253-AL-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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