Study of NMS-03597812 in Adult Patients With Relapsed/Refractory Acute Myeloid Leukemia
NCT Number: NCT06549790
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Relapsed/Refractory Acute Myeloid Leukemia
Interventions: DRUG: NMS-03597812
Sponsor: Nerviano Medical Sciences
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 124
Study Design: Allocation: NA|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08
Completion Date: 2030-05-15
Locations: Gabrail Cancer Research Center, Canton, Ohio, 44718-2566, United States

Summary:
The aim of PERKA-812-003 study is to investigate the safety, pharmacokinetics and preliminary anti-tumor activity of treatment with NMS-03597812 as single agent in Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) patients who have exhausted standard treatment, including a subset of patients with TP53 mutations. It is anticipated that combination with venetoclax will be further evaluated following a future protocol amendment, once the Recommended Range Dose (RDR) as single agent has been defined.

Primary Outcome Measures: Phase Ia (escalation) - Number of Participants with Adverse Events (AEs), Evaluation of AE frequency and severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] Version 5.0), including dose limiting toxicities (DLTs), laboratory measurements, electrocardiogram (ECG) measurements, vital sign measurements, Screening (Day ≤28) up to 28-day follow-up after end of treatment (Approximately 13 months)|Phase Ib (expansion) - Complete Remission (CR) rate, Complete Remission (CR) rate, as defined by the Investigators based on the 2022 European LeukemiaNet (ELN) recommendations, From date of treatment initiation up to hematological relapse (Approximately 12 months)
Secondary Outcome Measures: Phase Ia - Complete remission (CR) rate, Complete Remission (CR) rate, as defined by the Investigators based on the 2022 European LeukemiaNet (ELN) recommendations., From date of treatment initiation up to hematological relapse (Approximately 12 months)|Phase Ia - Maximum concentration (Cmax) of NMS-0597812, Plasma samples will be collected and used for pharmacokinetics assessments, Cycle 1 (each cycle is 28 days): Day 1 and Day 15|Phase Ia - Related time of achievement of occurrence of Cmax (tmax) of NMS-0597812, Plasma samples will be collected and used for pharmacokinetics assessments, Cycle 1 (each cycle is 28 days): Day 1 and Day 15|Trough concentration (Cτ) area under concentration versus time up to 24 hours (dosing interval) of NMS-0597812, Plasma samples will be collected and used for pharmacokinetics assessments, Cycle 1 (each cycle is 28 days): Day 1 and Day 15|Phase Ia - Half-life of the terminal phase (t½,z) of NMS-0597812, Plasma samples will be collected and used for pharmacokinetics assessments, Cycle 1 (each cycle is 28 days): Day 1 and Day 15|Phase Ia - Plasma clearance (CL) of NMS-0597812, Plasma samples will be collected and used for pharmacokinetics assessments, Cycle 1 (each cycle is 28 days): Day 1 and Day 15|Phase Ia - Volume of distribution (Vss) of NMS-0597812, Plasma samples will be collected and used for pharmacokinetics assessments, Cycle 1 (each cycle is 28 days): Day 1 and Day 15|Phase Ia - Accumulation ratio (Rac) of NMS-0597812, Plasma samples will be collected and used for pharmacokinetics assessments, Cycle 1 (each cycle is 28 days): Day 15|Phase Ia - Renal clearance (CLR) of NMS-03597812 excreted in urine (data permitting), Urine samples will be collected and used for pharmacokinetics assessments, Cycle 1 (each cycle is 28 days): Day 1 and Day 15|Phase Ia - Cumulative amount recovered unchanged in the urine (Ae) of NMS-03597812 (data permitting), Urine samples will be collected and used for pharmacokinetics assessments, Cycle 1 (each cycle is 28 days): Day 1 and Day 15|Phase Ia - Cumulative amount recovered unchanged in the urine expressed as a fraction of administered dose (Ae%) of NMS-03597812 (data permitting), Urine samples will be collected and used for pharmacokinetics assessments, Cycle 1 (each cycle is 28 days): Day 1 and Day 15|Phase Ib - Complete remission (CR) + complete remission with partial hematologic recovery (CRh) rate, Number and percentage of patients who achieve CR and CRh as best response, From date of treatment initiation up to hematological relapse (Approximately 12 months)|Phase Ib - Complete remission (CR) + Complete remission with incomplete hematologic recovery (CRi) rate, Number and percentage of patients who achieve CR and CRi as best response, From date of treatment initiation up to hematological relapse (Approximately 12 months)|Phase Ib - Complete remission (CR) + Complete remission with partial hematologic recovery (CRh) + complete remission with incomplete hematologic recovery (CRi) rate, Number and percentage of patients who achieve CR, CRh and CRi as best response, From date of treatment initiation up to hematological relapse (Approximately 12 months)|Phase Ib - Overall Response Rate (ORR: CR + CRh + CRi + MLFS + PR), ORR: Complete remission (CR) + Complete remission with partial hematologic recovery (CRh) + Complete remission with incomplete hematologic recovery (CRi) + Morphological leukemia-free state (MLFS) + Partial remission (PR)

Defined as the number and percentage of patients who achieve CR, CRh, CRi, MLFS and PR as best response in the analysis population, From date of treatment initiation up to hematological relapse/progressive disease (Approximately 12 months)|Phase Ib - Overall Survival (OS), Defined as the time from the date of start of treatment until the date of death from any cause. Patient who was not known to have died by the end of study will be censored at the date of last recorded date., First dose to the date of death from any cause or start of a new anti-cancer therapy, whichever comes first (Approximately 18 months)|Phase Ib - Duration of Response (DoR), Defined as the time from the date of first response (CR, CRh, or CRi) until the date of documented hematologic relapse or death due to progression. DOR will be also calculated for overall response, including patients who achieve MLFS or PR as best response during the treatment., From the date of first response (CR, CRh, or CRi) to the date of hematological relapse or death due to progression, whichever comes first. (Approximately 12 months)|Phase Ib - Event-Free Survival (EFS), Defined as the time from the date of treatment initiation to the date of hematological relapse from CR, CRh, or CRi, or death from any cause, whichever comes first., From the date of treatment initiation to the date of hematological relapse from CR, CRh, or CRi, date of treatment failure, or death from any cause, whichever comes first. (Approximately 18 months)|Phase Ib - Relapse-free Survival (RFS), Measured only for patients achieving CR, CRh, or CRi, and it is defined as the time from the date of first achievement of remission until the date of hematologic relapse or death from any cause., Date of first achievement of remission until the date of hematologic relapse or death from any cause, whichever comes first (Approximately 12 months).|Phase Ib - Proportion of patients bridged to hemopoietic stem cell transplantation (HSCT), From date of treatment initiation up to end of study (Approximately 18 months)|Phase Ib - Rate of conversion from transfusion-dependence to transfusion independence, From date of treatment initiation up to end of study (Approximately 18 months)|Phase Ib - AE frequency and severity, AE frequency and severity (graded using the National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] Version 5.0), laboratory, ECG and vital sign measurements, Screening (Day ≤28) up to 28-day follow-up after end of treatment (Approximately 13 months)