Safety and Clinical Activity of KT-253 in Adult Patients With High Grade Myeloid Malignancies, Acute Lymphocytic Leukemia, Lymphoma, Solid Tumors
Study Details
Study Description
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 |
|---|---|---|
| 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
Arms and Interventions
| 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
Primary Outcome Measures
- Incidence and severity of adverse events [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
- Maximum Tolerated Dose (MTD) and recommended Phase 2 dose (RP2D) in Patients [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
- 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)]
To determine the AUC from plasma concentrations in patients
- 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)]
To determine the Cmax from plasma concentrations in patients
- 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)]
To determine the Tmax from plasma concentrations in patients
- 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]
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)
- 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]
Hematological remission rate defined as CR and CRh per NCCN guidelines
- Evidence of Clinical activity of KT-253 in High-Risk Myelodysplastic syndromes (MDS) 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]
Complete remission (CR), partial remission (PR), Marrow CR and hematologic improvement (HI) per IWG criteria
- Evidence of Clinical activity of KT-253 in MDS/ Myeloproliferative Neoplasms (MPN) 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]
Percentage of patients with CR, PR, and Marrow Response per MDS/MPN IWG
- Evidence of Clinical activity of KT-253 in R/R Lymphoma patients [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
- Evidence of Clinical activity of KT-253 in R/R Solid Tumor patients [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
- Duration of Response (DOR) in 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]
Duration of Response (DOR) in R/R high grade myeloid malignancies and ALL, lymphoma and solid tumor patients treated with KT-253
Eligibility Criteria
Criteria
Inclusion Criteria:
- All Patients:
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Eastern Cooperative Oncology Group performance status: 0-2.
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Resolved acute effects of any prior therapy to baseline severity or Grade ≤1 NCI CTCAE
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Adequate organ and bone marrow function in the absence of growth factors
- Solid Tumors and Lymphoma (Arm A) ONLY
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Histologically or pathologically confirmed solid tumor or lymphoma.
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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
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Primary diagnosis of AML, ALL, Relapsed/progressed high-risk Myelodysplastic Syndromes (MDS), Myelodysplastic/myeloproliferative neoplasms (MDS/MPN). Must be relapsed/refractory to standard therapies.
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At least 4 weeks since radiotherapy prior to the first dose of study drug.
Exclusion Criteria:
- All Participants:
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Ongoing unstable cardiovascular function.
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Major surgery within 4 weeks of study entry.
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History of or active concurrent malignancy unless disease-free for ≥ 2 years.
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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.
- Solid Tumors and Lymphoma (Arm A) ONLY
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Known active uncontrolled or symptomatic central nervous system (CNS) metastases.
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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).
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Prior allogeneic hematopoietic stem cell transplant.
- Advanced high grade myeloid malignancies, and ALL (Arm B) ONLY
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Active CNS leukemia. Participants with symptoms suggestive of CNS disease will require a lumbar puncture to rule out CNS disease.
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Prior chemotherapy/radiation within ≤ 2 weeks of first dose of study drug
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Known systemic vasculitides (e.g., Wegener's granulomatosis, polyarteritis nodosa, systemic lupus erythematosus).
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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.
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Patients with active or chronic graft versus host disease (GVHD) or on treatment for GVHD.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Kymera Therapeutics, Inc.
Investigators
- Study Director: Ashwin Gollerkeri, MD, Kymera Therapeutics, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- KT253-AL-101