A Safety, Tolerability and Efficacy Study of NC525 in Subjects With Advanced Myeloid Neoplasms

NCT05787496 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: NC525-01
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 11

Brief Summary

This is an open-label, non-randomized, Phase 1 study to determine the safety and tolerability of NC525. This study will also assess the clinical benefit in subjects with advanced myeloid neoplasms.

Conditions

Relapsed or Refractory Acute Myeloid Leukemia; Relapsed or Refractory Chronic Myelomonocytic Leukemia; Relapsed or Refractory Myelodysplastic Syndrome

Keywords

Advanced Leukemia; Leukemia; NC525; PK; AML; MDS; CMML

Outcome Measures

Primary Outcomes (2)

• To Evaluate the Frequency, Duration, and Severity of Treatment-emergent Adverse Events [Safety and Tolerability].

  Toxicity grading per NCI CTCAE v5.0.

  Up to 23 months

• To Evaluate Dose-limiting Toxicities (DLTs) of NC525.

  Toxicity grading per NCI CTCAE v5.0.

  Up to 56 days

Secondary Outcomes (7)

• To Evaluate the Clinical Benefit of NC525 by Assessing Objective Response (OR).

  Until disease progression, up to 23 months

• To Evaluate the Clinical Benefit of NC525 by Assessing Event-free Survival (EFS).

  Until disease progression, up to 23 months

• To Evaluate the Clinical Benefit of NC525 by Assessing Overall Survival (OS).

  Time until death, up to 23 months

• Assessment of Time to Achieve Response, Defined as CR, CRi, or CRh

  Cycle 1 Day 1 to day remission is achieved, up to 23 months (each cycle is 28 days)

• Maximum Observed Serum Concentration (Cmax) of NC525

  During Cycles 1, 2, 3, 5, 7, and 11 (each cycle is 28 days)

Study Arms (6)

2mg/kg NC525

EXPERIMENTAL

Subjects received NC525 IV at 2mg/kg bi-weekly (Q2W) for Cycles 1-6, followed by every 4 weeks (Q4W) thereafter.

Drug: NC525

2.5mg/kg NC525

EXPERIMENTAL

Subjects received NC525 IV at 2.5mg/kg weekly (QW) until overall response (e.g., CR, CRh, or CRi) is achieved, at which time they may switch to Q2W dosing. Subjects in Cohort 2 initially received 3mg/kg weekly but dose was reduced to 2.5mg/kg weekly at FDA request due to change in dosing frequency from Q2W to QW.

Drug: NC525

4.5mg/kg NC525

EXPERIMENTAL

Subjects received NC525 IV at 4.5mg/kg weekly (QW) until overall response (e.g., CR, CRh, or CRi) is achieved, at which time they may switch to Q2W dosing.

Drug: NC525

9mg/kg NC525

EXPERIMENTAL

Subjects received NC525 IV at 9mg/kg weekly (QW) until overall response (e.g., CR, CRh, or CRi) is achieved, at which time they may switch to Q2W dosing.

Drug: NC525

13.5mg/kg NC525

EXPERIMENTAL

Subjects received NC525 IV at 13.5mg/kg weekly (QW) until overall response (e.g., CR, CRh, or CRi) is achieved, at which time they may switch to Q2W dosing.

Drug: NC525

18mg/kg NC525

EXPERIMENTAL

Subjects received NC525 IV at 18mg/kg weekly (QW) until overall response (e.g., CR, CRh, or CRi) is achieved, at which time they may switch to Q2W dosing.

Drug: NC525

Interventions

NC525 DRUG

Monoclonal antibody specific for LAIR-1

13.5mg/kg NC525; 18mg/kg NC525; 2.5mg/kg NC525; 2mg/kg NC525; 4.5mg/kg NC525; 9mg/kg NC525

Eligibility Criteria

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

You may qualify if:

• The subject is willing to provide written informed consent for the trial.
• Be ≥ 18 years of age on the day of signing informed consent.
• Subject has one of the following Myeloid Neoplasms determined by pathology review at the treating institution:
• Relapsed or Refractory AML, Note: Active, relapsed, or refractory AML is defined as any one of the following:
• Primary induction failure, or (PIF) after 2 or more cycles of therapy,
• First early relapse after a remission duration of fewer than 6 months,
• Relapse refractory to salvage combination chemotherapy second or subsequent relapse, or
• Relapsed or refractory AML with at least 5% blasts by bone marrow biopsy or aspirate, or at least 1% blasts in peripheral blood.
• Relapsed or Refractory Myelodysplastic syndrome (MDS) after prior hypomethylating agents.
• Note: Subject must have sub-type MDS-EB2 with 10-19% blasts by bone marrow biopsy or aspirate.
• Relapsed or Refractory Chronic myelomonocytic leukemia (CMML) with progressive disease or lack of response to hypomethylating agents
• A male subject must agree to use approved contraception (based on institutional guidelines) and refrain from sperm donation or expecting to father a child, from Screening through the treatment period and for at least 90 days after the last dose of study treatment.
• A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP);
• A WOCBP agrees to follow approved contraceptive guidance (based on institutional guidelines) from Screening through the treatment period and for at least 90 days after the last dose of study treatment.

You may not qualify if:

• Has a diagnosis of acute promyelocytic leukemia (M3, APL), accelerated phase or blast crisis of chronic myeloid leukemia.
• History or presence of clinically relevant CNS pathology such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
• Patients with active Central Nervous System (CNS) involvement (such as leukemic infiltration, blast in the spinal fluid, or subjects with extramedullary disease).
• A WOCBP who has a positive pregnancy test (within 72 hours) prior to treatment.
• History or evidence of any other clinically significant disorder, condition or disease (e.g., symptomatic congestive heart failure, unstable angina pectoris, symptomatic myocardial infection, uncontrolled cardiac arrhythmia, pericardial disease or heart failure New York Heart Association Class III or IV), or severe debilitating pulmonary disease, that would potentially increase patients' risk for toxicity and in the opinion of the Investigator, would pose a risk to patient safety or interfere with the study evaluation, procedures or completion.
• Chronic respiratory disease or any other medical condition that requires continuous oxygen that in the opinion of the Investigator, would adversely affect his/her participation in this study.
• Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
• Is currently participating in or has participated in a study of the following prior to the first dose of study treatment:
• An investigational biologic or an investigational device within 4 weeks or 5 half-lives (whichever is longer);
• An investigational oral agent within 2 weeks or 5 half-lives (whichever is shorter).
• Has not recovered to ≤ Grade 1 from toxic effects of prior therapy (including prior chemotherapy, immunotherapy and radiation therapy) and/or complications from interventions before starting therapy.
• Has previously had an allogeneic solid organ transplant.
• Autologous HSCT within 6 weeks before the start of study treatment.
• Allogeneic HSCT within 6 months before the start of study treatment.
• Any active acute or chronic graft-versus-host disease (GvHD), grade 2-4, or active chronic GvHD requiring systemic treatment.

Sponsors & Collaborators

• NextCure, Inc.: lead

Study Sites (11)

City of Hope

Duarte, California, 91010, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Weill Cornell Medicine

New York, New York, 10022, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Recurrence; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Leukemia

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease

Results Point of Contact

• Title: Chief Medical Officer
• Organization: NextCure, Inc

NCClin@nextcure.com

240-399-4900

Study Officials

• Han Myint, MD

  NextCure, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: February 8, 2023
• First Posted: March 28, 2023
• Study Start: February 28, 2023
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2025
• Last Updated: January 28, 2026
• Results First Posted: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)