A Safety and Tolerability Study of NC762 in Subjects With Advanced or Metastatic Solid Tumors

A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of NC762 in Subjects With Advanced or Metastatic Solid Tumors

This research study is studying a new drug, NC762, as a possible treatment for advanced or metastatic solid tumors.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer; Ovarian Cancer; Non-small Cell Lung Cancer; Advanced or Metastatic Solid Tumors
• Intervention / Treatment: Drug: NC762

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

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

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medicine and Biological Sciences
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Medical Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Carolina BioOncology Institute
  • Pennsylvania
    • Gettysburg, Pennsylvania, United States, 17325
      • Gettysburg Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Men and women aged 18 or older.
• Willingness to provide written informed consent for the study.
• ECOG performance status 0 to 1.
• Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.
• Subjects who have disease progression after treatment with available therapies that are known to confer clinical benefit, or who are intolerant to treatment, or who refuse standard treatment. Note: There is no limit to the number of prior treatment regimens.
• Presence of measurable disease based on RECIST v1.1. Tumor lesions situated in a previously irradiated area, or in an area subjected to other locoregional therapy, are not considered measurable unless there has been demonstrated progression in the lesion.
• Phase 1a Dose Escalation (optional), Phase 1b Safety Expansion, and Phase 2 (mandatory): Willingness to undergo pretreatment and on-treatment tumor biopsies (core or excisional).
• Female subjects of childbearing potential (defined as women who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy and are not postmenopausal, defined as ≥ 12 months of amenorrhea) and non-sterilized male subjects of childbearing potential must agree to take appropriate precautions to avoid pregnancy or fathering children (with at least 99% certainty) from screening through 90 days after the last dose of study drug. Females of child-bearing potential must have a negative serum pregnancy test at screening.

Exclusion Criteria:

• Inability to comprehend or unwilling to sign the ICF.

• Laboratory and medical history parameters not within the protocol-defined range.

  1. Absolute neutrophil count < 1.5 × 10^9/L.
  2. Platelets < 100 × 10^9/L.
  3. Hemoglobin < 9 g/dL or < 5.6 mmol/L.
  4. Serum creatinine > 1.5 × institutional upper limit of normal (ULN) and measured or calculated creatinine clearance < 50 mL/min for subjects with creatinine levels > 1.5 × institutional ULN.
  5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥ 2.5 × ULN. With the following exceptions: subjects with documented liver metastases AST and/or ALT ≤ 5 × ULN. Patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 ×ULN.
  6. Total bilirubin ≥ 1.5 × ULN.
  7. International normalized ratio (INR) or prothrombin time (PT) > 1.5 × ULN; Activated partial thromboplastin time (aPTT) > 1.5 × ULN, except for subjects on anticoagulation.
• Transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 7 days before the first administration of study drug.

• Receipt of anticancer medications or investigational drugs within the following intervals before the first administration of study drug:

  1. ≤ 14 days for chemotherapy, targeted small molecule therapy, hormonal therapy or radiation therapy. Subjects must not have had radiation pneumonitis because of a treatment. A 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease with medical monitor approval.
  2. ≤ 28 days for prior immunotherapy or persistence of active cellular therapy (e.g., chimeric antigen receptor T cell therapy; other cellular therapies must be discussed with the medical monitor to determine eligibility).
  3. ≤ 28 days for a prior mAb used for anticancer therapy except for denosumab.
  4. ≤ 7 days for immune-suppressive-based treatment for any reason.
  5. ≤ 28 days or 5 half-lives, t½, (whichever is longer) before the first dose for all other investigational study drugs or devices. For investigational agents with long half-lives (e.g., > 5 days), enrollment before the fifth t½ requires medical monitor approval.
  6. ≤ 14 days for a COVID-19 vaccine. Note: For 2-dose vaccines, subjects must wait at least 14 days after administration of the 2nd dose of the vaccine prior to receiving the first dose of the study drug.
• Has not recovered to ≤ Grade 1 from toxic effects of prior therapy (including prior immunotherapy and radiation therapy) and/or complications from prior surgical intervention before starting therapy.
• Receipt of a live vaccine within 30 days of planned start of study therapy.
• Active autoimmune disease that required systemic treatment in the past (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs).
• Known active CNS metastases and/or carcinomatous meningitis.
• Known concurrent malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry.
• Evidence of active, noninfectious pneumonitis or history of interstitial lung disease.
• Documented known activating or driver mutations (i.e. EGFR mutations/amplification, BRAF mutations, ALK alterations, etc.) which have not been previously treated with a standard of care targeted therapy.
• Subjects with screening QTc interval > 470 milliseconds (corrected by Fridericia) are excluded.
• Uncontrolled systemic fungal, bacterial, viral, or other infection despite appropriate anti-infection treatment.
• Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV), unless the hepatitis is considered to be cured.
• Known history of HIV (HIV 1 or HIV 2 antibodies).
• Known allergy or reaction to any component of study drug or formulation components.
• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 90 days after the last dose of study treatment.
• Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NC762 0.5mg/kg; Phase 1 Dose Escalation (Cohort 1): Subjects received NC762 IV at 0.5mg/kg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).	Drug: NC762; NC762 is an experimental antibody drug that may make the immune response more active against cancer
Experimental: NC762 1.5mg/kg; Phase 1 Dose Escalation (Cohort 2): Subjects received NC762 IV at 1.5mg/kg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).	Drug: NC762; NC762 is an experimental antibody drug that may make the immune response more active against cancer
Experimental: NC762 5mg/kg; Phase 1 Dose Escalation (Cohort 3): Subjects received NC762 IV at 5mg/kg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).	Drug: NC762; NC762 is an experimental antibody drug that may make the immune response more active against cancer
Experimental: NC762 10mg/kg; Phase 1 Dose Escalation (Cohort 4): Subjects received NC762 IV at 10mg/kg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).	Drug: NC762; NC762 is an experimental antibody drug that may make the immune response more active against cancer
Experimental: NC762 20mg/kg; Phase 1 Dose Escalation (Cohort 5): Subjects received NC762 IV at 20mg/kg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).	Drug: NC762; NC762 is an experimental antibody drug that may make the immune response more active against cancer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0	Frequency, duration, and severity of treatment-emergent adverse events (AEs)	Up to 15 months
Define a maximum tolerated dose (MTD) or pharmacologically active dose (PAD)	A 3 + 3 design will be utilized to determine the MTD of NC762	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate per RECIST	Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST(mRECIST) v1.1	Up to 15 months
Duration of Response per RECIST	Duration of Response (DoR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST (mRECIST) v1.1	Up to 15 months
Disease Control Rate per RECIST	Disease Control Rate (DCR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST (mRECIST) v1.1	Up to 15 months
Maximum Plasma Concentration (Cmax) of NC762	To evaluate the Maximum Plasma Concentration (Cmax) of NC762	Up to 15 months
Downregulation of B7-H4 expression and changes in tumor infiltrating lymphocytes	To evaluate downregulation of B7-H4 expression and changes in tumor infiltrating lymphocytes after NC762 treatment.	Up to 15 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2021
• Primary Completion (Actual): January 30, 2024
• Study Completion (Actual): January 30, 2024

Study Registration Dates

• First Submitted: May 3, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 6, 2021

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: Breast Cancer; Lung Cancer; Immunotherapy; PK; Ovarian Cancer; Solid Tumor; Advanced Cancer; Metastatic Cancer; NC762
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Ovarian Neoplasms
• Other Study ID Numbers: NC762-01

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