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

Advanced Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05775406
• Other study ID #: KT253-AL-101
• Status: Recruiting
• Phase: Phase 1
• Start date: May 15, 2023
• Est. completion date: November 2025

Study information

• Verified date: April 2024
• Source: Kymera Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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, 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: November 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphocytic Leukemia
• Advanced Solid Tumors
• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Lymphomas
• Myeloid Malignancies
• Neoplasms
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Inova Schar Cancer Institute	Fairfax	Virginia
United States	MD Anderson Cancer Center	Houston	Texas
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	OU Health Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	University of California, Davis Comprehensive Cancer Center	Sacramento	California
United States	HonorHealth Research Institute	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Kymera Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Area under the Plasma Concentration versus Time Curve (AUC) of KT-253	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)
Secondary	Maximum Plasma Concentration of KT-253 (Cmax)	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)
Secondary	Time to maximum plasma concentration of KT-253 (Tmax)	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)
Secondary	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.	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
Secondary	Evidence of Clinical activity of KT-253 in ALL patients	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
Secondary	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	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
Secondary	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	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
Secondary	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	From Baseline scan until first documented progression or death from any cause, whichever comes first , about 18 months
Secondary	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	From Baseline scan until first documented progression or death from any cause, whichever comes first, about 18 months
Secondary	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	From date of first of response to the date of documented first progression or death whichever comes first, about 18 months