Ph I Study in Adult Patients With Relapsed or Refractory Multiple Myeloma

NCT05027594 | Terminated Phase 1 FDA Drug

• 2 other identifiers: PERKA-812-0012020-004351-32
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase I, first-in-human (FIH), open-label, non-randomized, multi-center study to explore the safety, tolerability, pharmacokinetics and preliminary antitumor activity of NMS-03597812 in adult patients with RRMM who have exhausted standard treatment options that are expected to provide meaningful clinical benefit or for whom standard therapy is considered unsuitable.

Conditions

Multiple Myeloma

Keywords

Phase I; Multiple Myeloma; PERK inhibitor

Outcome Measures

Primary Outcomes (1)

• Number of Participants with first-cycle dose limiting toxicity

  For DLT evaluation, severity (grade) is classified according to common terminology criteria for adverse events version 5.0 (CTCAE v5.0).

  Time interval between the date of the first dose administration in Cycle 1 (each cycle is 28 days) and the date of the first dose administration in Cycle 2 which is expected to be 28 days or up to 42 days in case of dose delay due to toxicity

Secondary Outcomes (19)

• Number of participants with Adverse Events (AEs)

  From the Informed Consent signature to 28 days after the last dose of study treatment administration

• Number of Participants by Best Tumor response

  From treatment start date until disease progression or relapse (up to approximately 12 months).

• Number of Participants with Overall Response

  From treatment start date until disease progression or relapse (up to approximately 12 months).

• Number of Participants with Clinical Benefit

  From treatment start date until disease progression or relapse (up to approximately 12 months).

• Duration of Response

  From the first responding tumor assessment until Progression Disease/Relapse or Death due to Progression (up to approximately 12 months)

Study Arms (3)

Dose Escalation Part

EXPERIMENTAL

Patients with a confirmed diagnosis of relapsed or relapsed and refractory multiple myeloma (as per IMWG criteria) who have exhausted standard treatment options that are expected to provide meaningful clinical benefit or for whom standard therapy is considered unsuitable

Drug: NMS-03597812

Dose Expansion Part - NMS-03597812 single agent

EXPERIMENTAL

Patients with a confirmed diagnosis of relapsed or relapsed and refractory multiple myeloma (as per IMWG criteria) who have exhausted standard treatment options that are expected to provide meaningful clinical benefit or for whom standard therapy is considered unsuitable

Drug: NMS-03597812

Dose Expansion Part - NMS-03597812 in combination with dexamethasone

EXPERIMENTAL

Patients with a confirmed diagnosis of relapsed or relapsed and refractory multiple myeloma (as per IMWG criteria) who have exhausted standard treatment options that are expected to provide meaningful clinical benefit or for whom standard therapy is considered unsuitable

Drug: NMS-03597812 + dexamethasone

Interventions

NMS-03597812 DRUG

All patients will receive NMS-03597812 administered orally once daily on Days 1-21 in repeated 4-week cycles.

Dose Escalation Part; Dose Expansion Part - NMS-03597812 single agent

NMS-03597812 + dexamethasone DRUG

All patients will receive NMS-03597812 administered orally once daily on Days 1-21 and Dexamethasone administered orally once a week on Days 1, 8, 15 and 22 in repeated 4-week cycles.

Dose Expansion Part - NMS-03597812 in combination with dexamethasone

Eligibility Criteria

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

You may qualify if:

• Patients must have a confirmed diagnosis of relapsed or relapsed and refractory multiple myeloma (as per IMWG criteria)
• Patients must have exhausted available therapeutic options that are expected to provide meaningful clinical benefit, either through disease relapse, treatment refractory disease, intolerance or refusal of the therapy.
• Patients must have received at least three prior lines of therapy as defined by IMWG, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.
• Patients must have progressive/refractory disease to the last line of therapy.
• Patients must have measurable disease, defined as any of the following:serum monoclonal protein ≥ 0.5 g/dL by protein electrophoresis, ≥200 mg of monoclonal protein in urine on 24-h electrophoresis, or serum immunoglobulin free light chain ≥10 mg/dL with abnormal free-light-chain ratio.
• Adult (age ≥18 years) patients.
• Karnofsky performance status ≥60%.
• Adequate hematological profile, renal, hepatic and pancreatic functions
• All female patients with reproductive potential must have a negative pregnancy test (serum or urine) within the screening period prior to start of the study drug.
• Patients must use effective contraception or abstinence. Female patients of childbearing potential must agree to use effective contraception or abstinence during the period of therapy and in the following 90 days after discontinuation of study treatment. Male patients must be surgically sterile or must agree to use effective contraception or abstinence during the period of therapy and in the following 90 days after discontinuation of study treatment.
• Ability 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 IRB/EC-approved Informed Consent

You may not qualify if:

• Current enrollment in another interventional clinical study.
• Diagnosis of primary refractory multiple myeloma defined as disease that is non-responsive in patients who have never achieved a minimal response or better with any therapy
• Diagnosis of plasma cell leukemia, Waldenstrom's macroglobulinemia or amyloidosis.
• Diagnosis of non-secretory myeloma.
• Known central nervous system (CNS) involvement by multiple myeloma.
• Known history of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes (POEMS) syndrome.
• Currently active second malignancy, except for adequately treated basal or squamous cell skin cancer and/or conebiopsied in situ carcinoma of the cervix uteri and/or superficial bladder cancer.
• Autologous stem cell transplant ≤3 months prior to starting NMS-03597812.
• Prior allogeneic hematopoietic stem cell transplant (HSCT) with either standard or reduced intensity conditioning ≤6 months prior to starting NMS-03597812.
• Active acute or chronic graft versus host disease (GVHD) requiring immunosuppressive treatment. Patients who experienced GVHD requiring immunosuppressive treatment, must have stopped immunosuppressive treatment \>3 months prior to starting NMS-03597812.
• Any anticancer agent within 3 weeks (6 weeks for immunotherapy or nitrosoureas).
• Prior CAR-T cell \<3 months prior to starting NMS-03597812.
• Concomitant oral prednisone(or equivalent)\>10 mg/day. Doses of corticosteroid must have been stable for at least 7 days before startingNMS-03597812.
• Major surgery within 4 weeks before treatment start.
• Radiotherapy within 3 weeks prior to starting NMS-03597812. However, if the radiation portal covered ≤ 5% of the bone marrow reserve, the patient may be enrolled irrespective of the end date of radiotherapy.

Sponsors & Collaborators

• Nerviano Medical Sciences: lead

Study Sites (2)

Dana- Farber Cancer Institute

Boston, Massachusetts, 02215-5450, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204-2839, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Design

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

Model Details: Phase 1 Dose escalation part followed by a Dose Expansion part.

Study Record Dates

• First Submitted: August 25, 2021
• First Posted: August 30, 2021
• Study Start: September 9, 2022
• Primary Completion: August 8, 2023
• Study Completion: January 8, 2024
• Last Updated: June 13, 2025

Record last verified: 2025-06

Locations

US (2)