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Myeloid MalignanciesPhase 1NCT05775406

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

A Phase 1 study testing KT-253 in people with Myeloid Malignancies and Acute Lymphocytic Leukemia, run by Kymera Therapeutics, Inc. at 11 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
KT-253
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
11 sitesUnited States
Study dates
15 May 2023to 18 Dec 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 17Show fewer
  • 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.
  • 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.

Trial locations and contacts

11 sites in 1 country.

11 sites in 1 country

United States11 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Mary Crowley Cancer Research

    Dallas, Texas, 75230

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • Inova Schar Cancer Institute

    Fairfax, Virginia, 22031

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • OU Health Stephenson Cancer Center

    Oklahoma City, Oklahoma, 73104

  • University of California, Davis Comprehensive Cancer Center

    Sacramento, California, 95817

  • HonorHealth Research Institute

    Scottsdale, Arizona, 85258

  • Montefiore Medical Center

    The Bronx, New York, 10467

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
KT-253
Keywords
KT-253, MDM2, High Grade MDS/MPN, ALL, AML, Lymphoma, Solid tumor
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • KT-253Drug

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

Study groups in NCT05775406
Study groupRoleWhat they receive
Phase 1 Dose Escalation Arm A in patients with R/R Solid Tumors and LymphomasExperimentalKT-253 dosed intravenous (IV) once every three weeks in 21-day cycles
Receives: Drug: KT-253
Phase 1 Dose Escalation Arm B in patients with R/R High Grade Myeloid Malignancies and ALLExperimentalKT-253 dosed IV once every three weeks in 21-day cycles
Receives: Drug: KT-253

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: From the time of signing ICF through 30 days after last dose of study drug or prior to start of a new anticancer therapy

  2. 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

    Measured: 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)

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

    To determine the AUC from plasma concentrations in patients

    Measured: Blood samples for PK analysis collected up to Day15 during cycle 1 and cycle 2 (each cycle is 21 days)

  2. Maximum Plasma Concentration of KT-253 (Cmax)

    To determine the Cmax from plasma concentrations in patients

    Measured: Blood samples for PK analysis collected up to Day15 during cycle 1 and cycle 2 (each cycle is 21 days)

  3. Time to maximum plasma concentration of KT-253 (Tmax)

    To determine the Tmax from plasma concentrations in patients

    Measured: Blood samples for PK analysis collected up to Day15 during cycle 1 and cycle 2 (each cycle is 21 days)

  4. Evidence of Clinical Activity of KT-253 in AML patients

    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.

    Measured: 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

  5. Evidence of Clinical Activity of KT-253 in ALL patients

    Hematological remission rate defined as CR and CRh per NCCN guidelines

    Measured: 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

  6. Evidence of Clinical Activity of KT-253 in High/Very High-Risk Myelodysplastic syndromes (MDS) patients

    CR or CR equivalent, partial remission (PR),CR with limited count recovery, CRh, and hematologic improvement (HI) per revised International Working Group (IWG) criteria

    Measured: 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

  7. Evidence of Clinical Activity of KT-253 in MDS/ Myeloproliferative Neoplasms (MPN) patients

    Percentage of patients with CR, PR, and Marrow Response per MDS/MPN IWG

    Measured: 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

  8. Evidence of Clinical Activity of KT-253 in R/R Lymphoma patients

    Overall Response Rate (ORR) based on Investigator's assessment as per Lugano criteria 2014 for Lymphomas

    Measured: From Baseline scan until first documented progression or death from any cause, whichever comes first , about 18 months

  9. Evidence of Clinical Activity of KT-253 in R/R Solid Tumor patients

    Overall Response Rate (ORR) defined as percentage of patients with Complete Response or Partial Response per RECIST 1.1

    Measured: From Baseline scan until first documented progression or death from any cause, whichever comes first, about 18 months

  10. Duration of Response (DoR) in Patients Treated with KT-253

    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

    Measured: From date of first of response to the date of documented first progression or death whichever comes first, about 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Mar 2023
  2. Study start15 May 2023
  3. Primary completion18 Dec 2024
  4. Study completion18 Dec 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05775406
Sponsor's protocol ID
KT253-AL-101
Status last verified
Jan 2025
First submitted
10 Feb 2023
Last updated
27 Jan 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing KT-253 in people with Myeloid Malignancies and Acute Lymphocytic Leukemia, run by Kymera Therapeutics, Inc. at 11 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05775406.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2025.

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