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

A Phase 1, Open-Label, Safety, Tolerability, And Efficacy Study of NC525 in Subjects With Advanced Myeloid Neoplasms

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.

Study Overview

• Status: Recruiting
• Conditions: Relapsed or Refractory Acute Myeloid Leukemia; Relapsed or Refractory Chronic Myelomonocytic Leukemia; Relapsed or Refractory Myelodysplastic Syndrome
• Intervention / Treatment: Drug: NC525

• Study Type: Interventional
• Enrollment (Estimated): 63
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Director of Clinical Research; Phone Number: (240) 399-4900; Email: NelsonM@NextCure.com
• Study Contact Backup: Name: Director Clinical Operations at NextCure, Inc.; Phone Number: (240) 763-0535; Email: NCCLin@nextcure.com

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
      • Principal Investigator: Anthony Stein, MD
      • Contact: Samantha Humpal; Phone Number: 626-218-9401; Email: shumpal@coh.org
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami
      • Principal Investigator: Mikkael Sekeres, MD
      • Contact: Alessia Zoso; Email: azoso@miami.edu
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Principal Investigator: Amir Fathi, MD
      • Contact: Julie Supanekar; Phone Number: 617-724-5253; Email: jsupanekar@mgh.harvard.edu
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
      • Contact: Emma Logan; Email: eklogan@bidmc.harvard.edu
      • Principal Investigator: Margolzata McMasters
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine in St. Louis
      • Principal Investigator: John DiPersio, MD
      • Contact: Ayan Gasanli; Email: agasanli@wustl.edu
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Cancer Institute
      • Principal Investigator: Elizabeth Griffiths, MD
      • Contact: Layla Ortiz; Phone Number: 716-845-7559; Email: Layla.Ortiz@RoswellPark.org
    • New York, New York, United States, 10022
      • Recruiting
      • Weill Cornell Medicine
      • Contact: Penina Stewart; Email: pes4006@med.cornell.edu
      • Principal Investigator: Pinkal Desai, MD
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals Cleveland Medical Center
      • Principal Investigator: Benjamin Tomlinson, MD
      • Contact: Sarah Gollwitzer; Email: sarah.gollwitzer@uhhospitals.org
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: India Houston; Email: houstoi3@ccf.org
      • Principal Investigator: Moaath Ali, MD
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
      • Principal Investigator: Ronan Swords, MD
      • Contact: Lara Fournier; Email: trials@ohsu.edu
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
      • Contact: Danielle Nguyen; Phone Number: 713-792-4133; Email: dtnguyen7@mdanderson.org
      • Principal Investigator: Nicholas Short, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The subject is willing to provide written informed consent for the trial.
2. Be ≥ 18 years of age on the day of signing informed consent.

3. Subject has one of the following Myeloid Neoplasms determined by pathology review at the treating institution:

   1. 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.

   2. 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.

   3. Relapsed or Refractory Chronic myelomonocytic leukemia (CMML) with progressive disease or lack of response to hypomethylating agents
4. 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.

5. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:

   1. Not a woman of childbearing potential (WOCBP);
   2. 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.
6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
7. Life expectancy greater than or equal to 12 weeks as judged by the Investigator.
8. Have adequate organ function as defined in the protocol.

Exclusion Criteria:

1. Has a diagnosis of acute promyelocytic leukemia (M3, APL), accelerated phase or blast crisis of chronic myeloid leukemia.
2. 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.
3. Patients with active Central Nervous System (CNS) involvement (such as leukemic infiltration, blast in the spinal fluid, or subjects with extramedullary disease).
4. A WOCBP who has a positive pregnancy test (within 72 hours) prior to treatment.
5. 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.
6. 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.
7. Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.

8. Is currently participating in or has participated in a study of the following prior to the first dose of study treatment:

   1. An investigational biologic or an investigational device within 4 weeks or 5 half-lives (whichever is longer);
   2. An investigational oral agent within 2 weeks or 5 half-lives (whichever is shorter).
9. 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.
10. Has previously had an allogeneic solid organ transplant.
11. Autologous HSCT within 6 weeks before the start of study treatment.
12. Allogeneic HSCT within 6 months before the start of study treatment.
13. Any active acute or chronic graft-versus-host disease (GvHD), grade 2-4, or active chronic GvHD requiring systemic treatment.
14. Any systemic therapy (e.g. calcineurin inhibitors (CNI), steroids, etc.) against GvHD within 4 weeks before the start of study treatment.
15. Any Grade ≥ 2 persistent non-hematological toxicity related to allogeneic transplant, such as those requiring systemic immunosuppressive therapy.
16. Previous CAR-T therapy.
17. Known concurrent malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry after treatment with curative intent.
18. Has severe hypersensitivity (≥ Grade 3), known allergy or reaction to Immunoglobulins or NC525, and/or any of their excipients.
19. Uncontrolled systemic fungal, bacterial, viral, or other infection despite appropriate anti-infection treatment at the time of eligibility confirmation.
20. Has a known history of HIV infection.
21. Has a known active chronic hepatitis B infection or chronic hepatitis C infection with the exception of those with an undetectable viral load within 3 months.
22. Has a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the subject's participation for the full duration of the study, such that it is not in the best interest of the subject to participate, in the opinion of the treating investigator.
23. Has a known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NC525; Escalating dose levels will be explored.	Drug: NC525; Monoclonal antibody specific for LAIR-1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the frequency, duration, and severity of treatment-emergent adverse events [Safety and Tolerability].	Toxicity grading per NCI CTCAE v5.0.	Up to 24 months
To evaluate dose-limiting toxicities (DLTs) of NC525.	Toxicity grading per NCI CTCAE v5.0.	Up to 56 days
Define a recommended Phase 2 dose (RP2D) of NC525	A Bayesian Optimal Interval (BOIN) design will be utilized to determine a recommended Phase 2 dose (RP2D) for NC525.	Up to 24 months
Define a minimally active dose (MAD) of NC525	A BOIN design will be utilized to determine a MAD	Up to 24 months
Define a pharmacologically active dose (PAD) of NC525	A BOIN design will be utilized to determine a PAD	Up to 24 months
Define a maximum tolerated dose (MTD) of NC525	A BOIN design will be utilized to determine a MTD	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the clinical benefit of NC525 by assessing Objective Response (OR).	Disease Assessments will be performed using the European Leukemia Net (ELN) Guidelines for the ELN Outcome Measures.	Until disease progression, up to 24 months
To evaluate the clinical benefit of NC525 by assessing Event-free survival (EFS).	Disease Assessments will be performed using the European Leukemia Net (ELN) Guidelines for the ELN Outcome Measures.	Until disease progression, up to 24 months
To evaluate the clinical benefit of NC525 by assessing Overall survival (OS).	Disease Assessments will be performed using the European Leukemia Net (ELN) Guidelines for the ELN Outcome Measures.	Until disease progression, up to 24 months
Assessment of time to achieve response, defined as CR, CRi, or CRh	Disease Assessments will be performed using the European Leukemia Net (ELN) Guidelines for the ELN Outcome Measures.	Cycle 1 Day 1 to day remission is achieved, up to 24 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)
Terminal Half-life (t1/2) of NC525		During Cycles 1, 2, 3, 5, 7, and 11 (each cycle is 28 days)
Area under the serum concentration versus time curve (AUC) of NC525		During Cycles 1, 2, 3, 5, 7, and 11 (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: NextCure, Inc.
• Investigators: Study Director: Han Myint, MD, NextCure, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2023
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: February 8, 2023
• First Submitted That Met QC Criteria: March 14, 2023
• First Posted (Actual): March 28, 2023

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: AML; PK; Leukemia; MDS; CMML; Advanced Leukemia; NC525
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myeloid; Chronic Disease; Neoplasms; Myelodysplastic Syndromes; Leukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile
• Other Study ID Numbers: NC525-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No