Study of NMS-03597812 in Adult Patients With Relapsed/Refractory Acute Myeloid Leukemia

NCT06549790 | Recruiting Phase 1 FDA Drug

• 1 other identifier: PERKA-812-003
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Relapsed/Refractory Acute Myeloid Leukemia

Keywords

Leukemia; Relapsed/Refractory Acute Myeloid Leukemia; TP53 mutations

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (22)

• Phase Ia - Complete remission (CR) rate

  From date of treatment initiation up to hematological relapse (Approximately 12 months)

• Phase Ia - Maximum concentration (Cmax) of NMS-0597812

  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

  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

  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

  Cycle 1 (each cycle is 28 days): Day 1 and Day 15

Study Arms (1)

NMS-03597812

EXPERIMENTAL

Dose escalation (Phase Ia): Administered orally once daily (28 consecutive days) in repeated 4-week cycles. Each cycle is 28 days. Expansion cohorts (Phase Ib, Cohorts A and B): The dose expansion may comprise up to a total of 2 single arms of NMS-03597812 as single agent: * Cohort A: in patients with TP53mt relapsed/refractory acute myeloid leukemia (R/R AML) prior unfit to intensive chemotherapy (IC) who have exhausted standard treatment options * Cohort B: in prior fit or unfit patients to IC with TP53wt R/R AML who have exhausted standard treatment options Backfill cohorts: Optional backfill cohorts may be opened at any time during the conduct of the trial to further evaluate the following items: NMS-03597812 dosing alone, pharmacokinetic (PK), drug-drug interactions, food effects, biomarkers and QTc for NMS-03597812 as single agent.

Drug: NMS-03597812

Interventions

NMS-03597812 DRUG

Route of Administration: Oral

NMS-03597812

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed diagnosis of refractory/relapsed (R/R) AML according to 2022 ELN recommendation:
• Phase Ia
• single agent dose escalation of NMS-03597812: R/R AML patients who have exhausted standard therapy: a) prior fit patients to intensive chemotherapy (IC): failed at least one cycle of IC in front-line therapy or b) prior unfit to IC: failed at least 2 cycles of hypomethylating agents (HMA)/venetoclax combination therapy, or at least 4 cycles of HMA monotherapy; c) patients must have failed all other approved therapies for which they are eligible, including FLT3 inhibitors, IDH1/2 inhibitors, and CD33 directed therapy
• Phase Ib
• Cohort A: single agent in R/R AML TP53mt patients who have exhausted standard therapy: a) prior unfit to intensive chemotherapy (IC): failed at least 2 cycles of HMA/venetoclax combination therapy, or at least 4 cycles of HMA monotherapy; b) patients must have failed all other approved therapies for which they are eligible, including FLT3 inhibitors, IDH1/2 inhibitors, and CD33 directed therapy
• Cohort B: single agent in R/R AML TP53wt patients who have exhausted standard therapy: a) prior fit patients to intensive chemotherapy (IC): failed at least one cycle of IC in front-line therapy or b) prior unfit to IC: failed at least 2 cycles of HMA/venetoclax combination therapy, or at least 4 cycles of HMA monotherapy; c) patients must have failed all other approved therapies for which they are eligible, including FLT3 inhibitors, IDH1/2 inhibitors, and CD33 directed therapy
• Adult (age ≥ 18 years) patients
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Unless agreed with sponsor, the interval from prior antitumor treatment should be at least 2 weeks or 5 half-lives, whichever is longer, other than hydroxyurea
• All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to NCI CTCAE version 5.0 Grade≤ 1
• Adequate organ function
• Must use highly effective contraception or true abstinence. Female patients must be surgically sterile or, if patient is of childbearing potential, must agree to use effective contraception of therapy and in the following 210 days after discontinuation of study treatment. Since NMS-03597812 has potential induction of CYP3A4, women of childbearing potential must be advised that hormonal contraceptives might lose efficacy and must use alternate form of highly effective contraception. Male patients must be surgically sterile or must agree to use highly effective contraception or true abstinence during the period of therapy and in the following 120 days for male patients who must refrain from donating sperm during this period after discontinuation of study treatment.
• Capability to swallow capsules intact (without chewing, crushing, or opening)
• Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study indications or procedures
• Signed and dated Independent Ethics Committee (IEC) or Institutional Review Board (IRB)-approved informed consent form indicating that the patient is aware of the neoplastic nature of his/her disease and has been informed of the procedures to be followed, the investigational nature of the therapy, potential benefits, side effects, discomforts, risks, and alternative treatments.

You may not qualify if:

• Current enrollment in another interventional clinical study unless only participating in survival follow up
• White blood cells (WBC) count \>20×10\^3/microliter (μL). However, patients can be treated with hydroxyurea and/or leukapheresis prior to study treatment start to reduce the WBC to ≤ 20×10\^3/μL to enable eligibility for study drug dosing.
• Diagnosis of acute promyelocytic leukemia or BCR-ABL-positive leukemia
• Currently active second malignancy, except for adequately treated basal or squamous cell skin cancer and/or cone biopsied in situ carcinoma of the cervix uteri and/or superficial bladder cancer.
• Patients with known leukemia involvement of central nervous system (CNS).
• Hematopoietic stem cell transplantation (HSCT) within 3 months of treatment start and/or persistent non- hematologic toxicities of Grade ≥2 related to the transplant
• Active acute or chronic graft versus host disease (GVHD) requiring immunosuppressive treatment
• Patients with QTcF interval ≥ 470 milliseconds or with risk factors for torsade de pointes (e.g., uncontrolled heart failure, uncontrolled hypokalemia, history of prolonged QTc interval or family history of long QT syndrome). For patients receiving treatment with concomitant medications known to prolong the QTc interval, replacement with another treatment needs to be considered. If replacement or discontinuation is not clinically feasible, a careful risk/benefit evaluation should be performed prior to enrollment.
• Pregnancy. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) within the screening period prior to start of study drug.
• Breast-feeding or planning to breast feed during the study or within 90 days after study treatment.
• Known active gastrointestinal disease (eg, gastro-duodenal ulcer, gastrectomy, Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would impact on drug absorption.
• Patient who are receiving concomitant medications that are strong inducers or inhibitors of CYP3A4 (with the exception of azole antifungals) and CYP2C9 that cannot be replaced with alternative therapy.
• Patients who are receiving concomitant medications that are sensitive substrates of CYP3A4,CYP2D6, CYP1A2 and CYP2B6 with narrow therapeutic window that cannot be replaced with alternative therapy. Drugs with broad therapeutic indices may still be acceptable.
• Patients who are receiving concomitant medications that are strong or moderate P-gp inhibitors that cannot be replaced with alternative therapy.
• Major surgery within 4 weeks before study treatment start.

Sponsors & Collaborators

• Nerviano Medical Sciences: lead

Study Sites (7)

City of Hope - Duarte

Duarte, California, 91010, United States

RECRUITING

Rocky Mountain Cancer Centers

Aurora, Colorado, 80012, United States

RECRUITING

Medical Oncology Hematology Consultants

Newark, Delaware, 19713, United States

RECRUITING

Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, 30342, United States

RECRUITING

Mayo Clinic Cancer Center (MCCC) - Rochester

Rochester, Minnesota, 55905, United States

WITHDRAWN

Gabrail Cancer Research Center

Canton, Ohio, 44718, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Alberto Ocana

CONTACT

+39 0331-581111; clinicaltrials@nervianoms.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2024
• First Posted: August 12, 2024
• Study Start: October 16, 2024
• Primary Completion (Estimated): September 15, 2029
• Study Completion (Estimated): May 15, 2030
• Last Updated: October 31, 2025

Record last verified: 2025-10

Locations

US (7)