A Safety and Tolerability Study of NC318 in Subjects With Advanced or Metastatic Solid Tumors

• ClinicalTrials.gov Identifier: NCT03665285
• Recruitment Status: Recruiting
• First Posted: September 11, 2018
• Last Update Posted: August 18, 2021
• Sponsor: NextCure, Inc.
• Information provided by (Responsible Party): NextCure, Inc.

Study Description

Brief Summary:

This research study is studying a new drug, NC318, as a possible treatment for advanced or metastatic solid tumors.

Condition or disease	Intervention/treatment	Phase
Advanced or Metastatic Solid Tumors; Non-Small Cell Lung Cancer; Breast Cancer; Head and Neck Squamous Cell Carcinoma	Drug: NC318	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 173 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of NC318 in Subjects With Advanced or Metastatic Solid Tumors
• Actual Study Start Date: September 28, 2018
• Estimated Primary Completion Date: December 15, 2023
• Estimated Study Completion Date: December 15, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: NC318; NC318 for IV infusion of various dose strengths administered in 14 day dosing cycles. Alternative dosing schedules may be explored once RP2D has been determined.	Drug: NC318; NC318 is an experimental antibody drug that may make the immune response more active against cancer.

Outcome Measures

Primary Outcome Measures :

1. Number of participants with treatment-emergent Adverse Events as assessed by CTCAE v5.0 [ Time Frame: up to 14 months ]
   Frequency, duration, and severity of treatment-emergent adverse events (AEs)
2. Define a maximum tolerated dose (MTD) or pharmacologically active dose (PAD) [ Time Frame: 28 days ]
   A 3 + 3 design will be utilized to determine the MTD of NC318

Secondary Outcome Measures :

1. Disease Response as assessed by RECIST 1.1 and mRECIST [ Time Frame: up to 14 months ]
   Assessing objective response rate (ORR), duration of response (DoR), and disease control rate (DCR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST (mRECIST) v1.1
2. Maximum Plasma Concentration (Cmax) of NC318 [ Time Frame: 14 weeks ]
   To evaluate the Maximum Plasma Concentration (Cmax) of NC318
3. Area Under the Curve (AUC) of NC318 [ Time Frame: 14 weeks ]
   To evaluate the Area Under the Curve (AUC) of NC318
4. Half-life (t1/2) of NC318 [ Time Frame: 14 weeks ]
   To evaluate the half-life (t1/2) of NC318

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Men and women aged 18 or older.
• Willingness to provide written informed consent for the study.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
• Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.
• Subjects with advanced or metastatic head and neck squamous cell carcinoma, non-small cell lung cancer, and breast cancer who are Siglec-15 positive.
• 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.
• Willing 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) must have a negative serum pregnancy test at screening. All female and 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 60 days after the last dose of study drug.

Exclusion Criteria:

• Inability to comprehend or unwilling to sign the Informed Consent Form.

• Screening laboratory values of:

  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)
  5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≥ 2.5 × ULN
  6. Total bilirubin ≥ 1.5 × ULN.
  7. International normalized ratio (INR) or prothrombin time (PT) > 1.5 × ULN
  8. Activated partial thromboplastin time (aPTT) > 1.5 × ULN
• 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, or radiation therapy. Subjects must also not require chronic use of corticosteroids and 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. Note: Bisphosphonates and denosumab are permitted medications.
  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 monoclonal antibody used for anticancer therapy except for denosumab.
  4. ≤ 7 days for immune-suppressive-based treatment for any reason. Note: Use of inhaled or topical steroids or corticosteroid use for radiographic procedures is permitted. Note: The use of physiologic corticosteroid replacement therapy may be approved after consultation with the medical monitor.
  5. ≤ 28 days or 5 half-lives (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 half-life requires medical monitor approval.
  6. ≤ 14 days for COVID-19 vaccine.
• Has not recovered to ≤ Grade 1 from toxic effects of prior therapy (including prior immunotherapy) and/or complications from prior surgical intervention before starting therapy. Note: Subjects with stable chronic conditions (≤ Grade 2) not expected to resolve (such as neuropathy and alopecia) are exceptions and may enroll. Note: Subjects with a history of any grade immune-related ocular AE (e.g., episcleritis, scleritis, uveitis) will be excluded.
• Receipt of a live vaccine within 30 days of planned start of study therapy. Note: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox/zoster, yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• Active autoimmune disease that required systemic treatment in the past (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Note: Subjects with hyperthyroidism or hypothyroidism, who have not required systemic treatment for an autoimmune disease for at least 2 years and are stable on thyroid hormone replacement are allowed to participate in the study. Note: Replacement and symptomatic therapies (e.g., levothyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) are not considered a form of systemic immune suppressive therapy and are allowed.
• Known active CNS metastases and/or carcinomatous meningitis. Note: Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 28 days before the first dose of study drug and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases or CNS edema, and have not required steroids for at least 7 days before the first dose of study drug.
• Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry after treatment with curative intent. Note: Cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, or cancers from which the subject has been disease-free for > 1 year are not considered exclusionary.
• Evidence of active, noninfectious pneumonitis or history of interstitial lung disease.
• History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's opinion, is clinically meaningful.
• 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 60 days after the last dose of study treatment.

Contacts and Locations

Contacts

Contact: Associate Director of Clinical Operations at NextCure, Inc.; 240-763-0535; NCClin@NextCure.com

Contact: Director of Clinical Research; (240) 399-4900; NelsonM@NextCure.com

Locations

United States, California

The Angeles Clinic and Research Institute; Recruiting

Los Angeles, California, United States, 90025

Contact: Saba Mukarram 310-582-7900 SMukarram@theangelesclinic.org

Principal Investigator: Omid Hamid, MD

United States, Connecticut

Yale University Cancer Center; Completed

New Haven, Connecticut, United States, 06510

United States, New Jersey

John Theurer Cancer Center at Hackensack University Medical Center; Recruiting

Hackensack, New Jersey, United States, 07601

Contact: Chelsea McCabe 551-996-5863 Chelsea.McCabe@hackensackmeridian.org

Principal Investigator: Martin Gutierrez, MD

United States, New York

Laura and Isaac Perlmutter Cancer Center; Recruiting

New York, New York, United States, 10016

Contact: Elaine Shum, MD 212-731-5662

Principal Investigator: Elaine Shum, MD

United States, Texas

NEXT Oncology; Recruiting

San Antonio, Texas, United States, 78240

Contact: Cynthia De Leon 210-580-9521 cdeleon@nextoncology.com

Principal Investigator: Anthony W. Tolcher, MD

Sponsors and Collaborators

NextCure, Inc.

Investigators

• Study Director: Han Myint, MD; NextCure, Inc.

More Information

• Responsible Party: NextCure, Inc.
• ClinicalTrials.gov Identifier: NCT03665285
• Other Study ID Numbers: NC318-01
• First Posted: September 11, 2018
• Last Update Posted: August 18, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by NextCure, Inc.:

Advanced Cancer; Metastatic Cancer; Head and Neck Squamous Cell Carcinoma; Non Small Cell Lung Cancer; NC318; Immunotherapy; PD-L1; dose escalation; biomarker; PK; cohort expansion; Solid Tumor

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplasms, Squamous Cell; Head and Neck Neoplasms