NMS-03597812 for AML

Recruiting at 5 trial locations

Overseen By Alberto Ocana

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Nerviano Medical Sciences

Must not be taking: Antacids, CYP3A4 inducers

Disqualifiers: Active second malignancy, CNS leukemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

124 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, NMS-03597812, to determine its safety and effectiveness for people with relapsed or refractory acute myeloid leukemia (R/R AML), a type of blood cancer unresponsive to other treatments. Researchers aim to assess the drug's effects, particularly in individuals with a specific mutation in their TP53 gene. Those who have tried all approved treatments for R/R AML without success may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking certain medications, especially those that affect specific enzymes (like CYP3A4) or prolong the QTc interval, unless they can be replaced with alternatives. You should discuss your current medications with the trial team to see if any changes are needed.

Is there any evidence suggesting that NMS-03597812 is likely to be safe for humans?

Research shows that NMS-03597812 is a new treatment being tested for safety in people with acute myeloid leukemia (AML), a type of blood cancer. This treatment is in the early stages of testing, with the main goal of determining its safety for humans. Detailed information on how well people tolerate it or what side effects it might cause remains limited.

As a Phase 1 trial, scientists focus on ensuring the treatment's safety, finding the right dose, and monitoring for negative reactions. Phase 1 trials usually involve a small number of participants, so not all side effects may be known yet.

NMS-03597812 works by blocking certain proteins that cancer cells need to grow. However, because the trials are in early stages, complete safety information is not fully known. Participants should consider this when deciding to join the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for AML?

Unlike the standard treatments for acute myeloid leukemia (AML), which often include intensive chemotherapy and stem cell transplants, NMS-03597812 offers a new approach. This treatment is unique because it targets specific genetic mutations, like TP53, that are often resistant to conventional therapies. Administered orally, NMS-03597812 provides a less invasive option, which could make treatment more accessible and tolerable for patients who are not fit for intensive treatments. Researchers are excited about its potential to address unmet medical needs in patients who have exhausted standard treatment options.

What evidence suggests that NMS-03597812 might be an effective treatment for AML?

Research suggests that NMS-03597812, which participants in this trial may receive, could help treat relapsed or hard-to-treat acute myeloid leukemia (AML). This drug blocks certain proteins, PERK and GCN2, that aid tumor growth. Early lab studies have shown that it can effectively fight tumors alone or in combination with other treatments. Additionally, targeting genes like FLT3, often altered in some AML patients, may improve treatment outcomes. Although human studies provide limited information, these early findings indicate that NMS-03597812 might be effective against AML. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with Acute Myeloid Leukemia (AML) that has come back or didn't respond to standard treatments. It's also looking at a subgroup of these patients who have specific genetic changes called TP53 mutations.

Inclusion Criteria

I am willing and able to follow the study's schedule and procedures.

I haven't had cancer treatment for at least 2 weeks or 5 half-lives, except for hydroxyurea.

Signed and dated Independent Ethics Committee (IEC) or Institutional Review Board (IRB)-approved informed consent form

Exclusion Criteria

Patients with QTcF interval ≥ 470 milliseconds or with risk factors for torsade de pointes

I have a digestive system disease that affects food absorption.

I am taking medications that are sensitive to certain enzymes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment Phase Ia (Dose Escalation)

Participants receive NMS-03597812 orally once daily in repeated 4-week cycles to determine the Recommended Range Dose (RDR)

28 days per cycle, multiple cycles

Cycle 1: Day 1 and Day 15 visits (in-person)

Treatment Phase Ib (Dose Expansion)

Dose expansion in cohorts A and B to evaluate NMS-03597812 in specific patient subgroups

12 months

Regular visits throughout treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

28-day follow-up after end of treatment

What Are the Treatments Tested in This Trial?

Interventions

• NMS-03597812

Trial Overview The study tests NMS-03597812, a new potential treatment for AML. Initially, it's given alone to determine safety and dosage; later, it may be combined with another drug called venetoclax after further review.

How Is the Trial Designed?

Group I: NMS-03597812 Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Nerviano Medical Sciences

Lead Sponsor

Trials

14

Recruited

770+

Published Research Related to This Trial

Recent advancements in treatments for acute myeloid leukemia (AML), including new drugs like midostaurin and venetoclax, have improved post-remission therapy options for both younger and older patients, changing the approach to consolidation therapy.

The measurement of measurable residual disease (MRD) is now being used to tailor treatment plans, helping to determine the best duration and type of therapy, as well as the timing for allogeneic hematopoietic cell transplantation (allo-HCT).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Induction Treatment for Acute Myeloid Leukemia: Something Change? Jaramillo, S., Schlenk, RF.[2023]

Glasdegib, a smoothened (SMO) inhibitor, has been approved by the FDA and EMA for treating naïve acute myeloid leukemia (AML) patients who are not suitable for intensive chemotherapy, showing efficacy in controlling the disease when combined with low-dose cytarabine.

Clinical studies indicate that glasdegib has a favorable safety profile and may enhance the effectiveness of both traditional chemotherapy and biological treatments, such as FLT3 inhibitors, although further research is needed to identify which patients will benefit the most.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glasdegib for the treatment of acute myeloid leukemia. Bruzzese, A., Martino, EA., Labanca, C., et al.[2023]

Next generation sequencing (NGS) has significantly advanced the understanding of acute myeloid leukemia (AML) by identifying genetic mutations and precursor lesions, which are now influencing treatment decisions and patient stratification.

The integration of genetic profiling into clinical practice is expected to enhance diagnosis, risk assessment, and the development of personalized treatment plans, including the use of recently approved drugs targeting specific genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next Generation Sequencing in AML-On the Way to Becoming a New Standard for Treatment Initiation and/or Modulation? Leisch, M., Jansko, B., Zaborsky, N., et al.[2020]

In a study of 75 newly diagnosed acute myeloid leukaemia (AML) patients, those with FLT3 mutations had a complete remission rate of 69.2% after standard induction chemotherapy, which is slightly lower than the 77.4% rate in FLT3-negative patients.

Despite the presence of FLT3 mutations, there were no significant differences in overall survival or relapse rates between FLT3-positive and FLT3-negative groups, suggesting that FLT3 status may not be a determining factor in treatment outcomes for AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Patients with FLT3 Positive Acute Myeloid Leukaemia; an Experience from a Tertiary Care Hospital in Karachi, Pakistan. Zulfiqar, M., Ali, N., Shaikh, U., et al.[2023]

Approximately 30% of adult patients with acute myeloid leukemia (AML) have mutations in the FLT3 gene, which significantly worsen their prognosis, highlighting the importance of genetic testing in treatment planning.

Targeting FLT3 with investigational therapies could transform AML treatment by specifically inhibiting the growth of cancer cells while sparing normal cells, paving the way for more personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FLT3 inhibitors in the treatment of acute myeloid leukemia: the start of an era? Pemmaraju, N., Kantarjian, H., Ravandi, F., et al.[2021]

Citations

1. sigma.larvol.com sigma.larvol.com/product.php?e1=1023692&tab=newstrac

NMS-812 News NMS-812, a novel potent PERK inhibitor that also inhibits GCN2, exhibits strong anti-tumor activity as single agent and in combination in preclinical models ( ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06549790

NCT06549790 | Study of NMS-03597812 in Adult Patients ... 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 ...

3. withpower.com withpower.com/trial/nms-03597812-for-aml-0752e

NMS-03597812 for AML · Recruiting Participants for Phase ... Research shows that drugs targeting the FLT3 gene, which is mutated in about 30% of AML patients, can potentially improve treatment outcomes. FLT3 inhibitors, ...

4. ctsearchsupport.org ctsearchsupport.org/clinical-trials/study-of-nms-03597812-in-adult-patients-with-relapsed-refractory-acute-myeloid-leukemia

A drug, NMS-03597812, to treat acute myeloid leukemia ... To find out:The highest dose of NMS-03597812 that's safe to giveIf NMS-03597812 is safe and works well to treat AML that has relapsed or is refractory.

5. dana-farber.org dana-farber.org/clinical-trials/21-147

A Phase I Dose Escalation Study of NMS-03597812, ... This is a Phase I, first-in-human (FIH), open-label, non-randomized, multi-center study to explore the safety, tolerability, pharmacokinetics and preliminary ...

6. nervianoms.com nervianoms.com/nerviano-medical-sciences-announces-fda-protocol-clearance-of-new-ind-application-for-nms-812-a-first-in-class-dual-inhibitor-of-perk-gcn2-brian-sherer-phd-appointed-to-lead-and-accelerate-the-dev/

Nerviano Medical Sciences announces FDA protocol ... The United States Food and Drug Administration (FDA) has cleared the protocol for investigational new drug (IND) application for NMS-812.

7. nmsgroup.it nmsgroup.it/wp-content/uploads/2024/06/20240624-NMS-PERK-Study-May-Proceed-Brian-Sherer-as-AL-Final.pdf

Nerviano Medical Sciences announces FDA protocol ... NMS-812: A clinical phase potent and selective PERK/GCN2 inhibitor, a potential first-in-class targeting the integrated stress response (ISR).

8. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2024-0443.html

A phase Ia/Ib study of NMS-03597812 in adult patients with ... 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 ...