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

NCT05775406 | Completed Phase 1 FDA Drug

• 1 other identifier: KT253-AL-101
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 11

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, myelofibrosis, and R/R solid tumors. The study will identify the pharmacologically optimal dose(s) (MTD) of KT-253 as the recommended Phase 2 dose (RP2D), based on all safety, PK, PD, and efficacy data.

Conditions

Myeloid Malignancies; Acute Lymphocytic Leukemia; Lymphomas; Advanced Solid Tumors

Keywords

KT-253; MDM2; High Grade MDS/MPN; ALL; AML; Lymphoma; Solid tumor

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of adverse events

  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

  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 Outcomes (10)

• Area under the Plasma Concentration versus Time Curve (AUC) of KT-253

  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)

  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)

  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 AML patients

  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 ALL patients

  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

Study Arms (2)

Phase 1 Dose Escalation Arm A in patients with R/R Solid Tumors and Lymphomas

EXPERIMENTAL

KT-253 dosed intravenous (IV) once every three weeks in 21-day cycles

Drug: KT-253

Phase 1 Dose Escalation Arm B in patients with R/R High Grade Myeloid Malignancies and ALL

EXPERIMENTAL

KT-253 dosed IV once every three weeks in 21-day cycles

Drug: KT-253

Interventions

KT-253 DRUG

KT-253 will be administered intravenously per the defined protocol frequency and dose level.

Phase 1 Dose Escalation Arm A in patients with R/R Solid Tumors and Lymphomas; Phase 1 Dose Escalation Arm B in patients with R/R High Grade Myeloid Malignancies and ALL

Eligibility Criteria

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

You may qualify if:

• 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
• 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.
• 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.

You may not qualify if:

• 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.
• Known presence of p53 mutations in tumor tissue or blood, which are known to completely inactivate p53 transcriptional activity
• 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).
• Exposures to anticancer therapy or investigational therapy within 2 weeks or 5 half-lives whichever is longer prior to the first dose of study drug.
• Received immunotherapy/biologic treatment or investigational therapy within 4 weeks prior to first dose of KT-253, including tumor vaccines and checkpoint inhibitors.
• Advanced high grade myeloid malignancies, and Acute Lymphocytic Leukemia (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.

Sponsors & Collaborators

• Kymera Therapeutics, Inc.: lead

Study Sites (11)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

University of California, Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

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: February 10, 2023
• First Posted: March 20, 2023
• Study Start: May 15, 2023
• Primary Completion: December 18, 2024
• Study Completion: December 18, 2024
• Last Updated: January 27, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)