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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05775406
Recruitment Status : Recruiting
First Posted : March 20, 2023
Last Update Posted : May 22, 2023
Sponsor:
Information provided by (Responsible Party):
Kymera Therapeutics, Inc.

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Myeloid Malignancies Acute Lymphocytic Leukemia Lymphomas Advanced Solid Tumors Drug: KT-253 Phase 1

Detailed Description:
This is an open-label Phase 1 (dose escalation) first-in-human study of KT-253 in adult patients. This study will be initiated in patients with advanced high-grade myeloid malignancies, ALL, lymphomas, and solid tumors and will be 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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 15, 2023
Estimated Primary Completion Date : November 2024
Estimated Study Completion Date : November 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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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.


Outcome Measures
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Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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 International Working Group (IWG)

  5. 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

  6. Evidence of Clinical activity of KT-253 in 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 ]
    Complete remission (CR), partial remission (PR), Marrow CR and hematologic improvement (HI) per IWG criteria

  7. 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

  8. 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

  9. 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

  10. 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, lymphoma and solid tumor patients treated with KT-253


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. All Patients:

    • Eastern Cooperative Oncology Group performance status: 0-2.
    • Resolved acute effects of any prior therapy to baseline severity or Grade ≤1 NCI CTCAE
    • Adequate organ and bone marrow function in the absence of growth factors

  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, Relapsed/progressed high-risk Myelodysplastic Syndromes (MDS), Myelodysplastic/myeloproliferative neoplasms (MDS/MPN). Must be relapsed/refractory to standard therapies.
    • At least 4 weeks since radiotherapy prior to the first dose of study drug.

Exclusion Criteria:

  1. All Participants:

    • Ongoing unstable cardiovascular function.
    • Major surgery within 4 weeks of study entry.
    • 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.

  2. Solid Tumors and Lymphoma (Arm A) ONLY

    • Known active uncontrolled or symptomatic central nervous system (CNS) metastases.
    • Autologous 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).
    • Prior allogeneic hematopoietic stem cell transplant.

  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 within ≤ 2 weeks of first dose of study drug
    • Known systemic vasculitides (e.g., Wegener's granulomatosis, polyarteritis nodosa, systemic lupus erythematosus).
    • Participant is within 3 months post allogenic hematopoietic stem cell transplant or within 30 days post autologous stem cell transplant, and the participant has not recovered from transplant-associated toxicities.
    • Patients with active or chronic graft versus host disease (GVHD) or on treatment for GVHD.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05775406


Locations
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United States, Arizona
HonorHealth Research Institute Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Oncology Clinical Trials Nurse Navigator    480-323-1791    clinicaltrials@honorhealth.com   
United States, Texas
Mary Crowley Cancer Research Recruiting
Dallas, Texas, United States, 75230
Contact: Reva Schneider, MD    972-566-3000    referral@marycrowley.org   
Sponsors and Collaborators
Kymera Therapeutics, Inc.
Investigators
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Study Director: Ashwin Gollerkeri, MD Kymera Therapeutics, Inc.
More Information
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Responsible Party: Kymera Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05775406    
Other Study ID Numbers: KT253-AL-101
First Posted: March 20, 2023    Key Record Dates
Last Update Posted: May 22, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kymera Therapeutics, Inc.:
KT-253
MDM2
High Grade MDS/MPN
ALL
 AML
Lymphoma
Solid tumor
Additional relevant MeSH terms:
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Lymphoma
Neoplasms
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
 Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases