Trial Title:
Safety and Clinical Activity of KT-253 in Adult Patients with High Grade Myeloid Malignancies, Acute Lymphocytic Leukemia, Lymphoma, Solid Tumors
NCT ID:
NCT05775406
Condition:
Myeloid Malignancies
Acute Lymphocytic Leukemia
Lymphomas
Advanced Solid Tumors
Conditions: Official terms:
Lymphoma
Neoplasms
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Conditions: Keywords:
KT-253
MDM2
High Grade MDS/MPN
ALL
AML
Lymphoma
Solid tumor
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Active, not recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
KT-253
Description:
KT-253 will be administered intravenously per the defined protocol frequency and dose
level.
Arm group label:
Phase 1 Dose Escalation Arm A in patients with R/R Solid Tumors and Lymphomas
Arm group label:
Phase 1 Dose Escalation Arm B in patients with R/R High Grade Myeloid Malignancies and ALL
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.
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.
Criteria for eligibility:
Criteria:
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.
- Known presence of p53 mutations in tumor tissue or blood, which are known to
completely inactivate p53 transcriptional activity
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).
- 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.
3. 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
HonorHealth Research Institute
Address:
City:
Scottsdale
Zip:
85258
Country:
United States
Facility:
Name:
University of California, Davis Comprehensive Cancer Center
Address:
City:
Sacramento
Zip:
95817
Country:
United States
Facility:
Name:
Dana Farber Cancer Institute
Address:
City:
Boston
Zip:
02215
Country:
United States
Facility:
Name:
Henry Ford Health System
Address:
City:
Detroit
Zip:
48202
Country:
United States
Facility:
Name:
Montefiore Medical Center
Address:
City:
Bronx
Zip:
10467
Country:
United States
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Facility:
Name:
OU Health Stephenson Cancer Center
Address:
City:
Oklahoma City
Zip:
73104
Country:
United States
Facility:
Name:
Mary Crowley Cancer Research
Address:
City:
Dallas
Zip:
75230
Country:
United States
Facility:
Name:
University of Texas Southwestern Medical Center
Address:
City:
Dallas
Zip:
75390
Country:
United States
Facility:
Name:
MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Facility:
Name:
Inova Schar Cancer Institute
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Start date:
May 15, 2023
Completion date:
November 2025
Lead sponsor:
Agency:
Kymera Therapeutics, Inc.
Agency class:
Industry
Source:
Kymera Therapeutics, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05775406
