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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03665285
Recruitment Status : Recruiting
First Posted : September 11, 2018
Last Update Posted : November 13, 2019
Sponsor:
Information provided by (Responsible Party):
NextCure, Inc.

Tracking Information
First Submitted Date  ICMJE September 6, 2018
First Posted Date  ICMJE September 11, 2018
Last Update Posted Date November 13, 2019
Actual Study Start Date  ICMJE September 28, 2018
Estimated Primary Completion Date May 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 7, 2018)
  • 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)
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 7, 2018)
  • 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
  • Maximum Plasma Concentration (Cmax) of NC318 [ Time Frame: 14 weeks ]
    To evaluate the Maximum Plasma Concentration (Cmax) of NC318
  • Area Under the Curve (AUC) of NC318 [ Time Frame: 14 weeks ]
    To evaluate the Area Under the Curve (AUC) of NC318
  • Half-life (t1/2) of NC318 [ Time Frame: 14 weeks ]
    To evaluate the half-life (t1/2) of NC318
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Safety and Tolerability Study of NC318 in Subjects With Advanced or Metastatic Solid Tumors
Official Title  ICMJE A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of NC318 in Subjects With Advanced or Metastatic Solid Tumors
Brief Summary This research study is studying a new drug, NC318, as a possible treatment for advanced or metastatic solid tumors.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced or Metastatic Solid Tumors
  • Head and Neck Squamous Cell Carcinoma
  • Non-Small Cell Lung Cancer
  • Ovarian Cancer
  • Triple Negative Breast Cancer
Intervention  ICMJE Drug: NC318
NC318 is an experimental antibody drug that may make the immune response more active against cancer.
Study Arms  ICMJE Experimental: NC318
NC318 for injection of various dose strengths administered in 14 day dosing cycles
Intervention: Drug: NC318
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 11, 2019)
143
Original Estimated Enrollment  ICMJE
 (submitted: September 7, 2018)
110
Estimated Study Completion Date  ICMJE May 1, 2021
Estimated Primary Completion Date May 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 PD-L1 low advanced or metastatic head and neck squamous cell carcinoma, non-small cell lung cancer, ovarian cancer, and triple negative breast cancer.
  • 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.
  • After dose escalation, subject must be willing to undergo pretreatment and on-treatment tumor biopsies (core or excisional). Note: A baseline biopsy obtained for other purposes (i.e., not an NC318-01 study procedure) before signing consent may be utilized if the subject has not had any intervening systemic therapy from the time of the biopsy to the start of treatment with the medical monitor's approval.
  • 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 unless conjugated bilirubin ≤ ULN (conjugated bilirubin only needs to be tested if total bilirubin exceeds ULN). If there is no institutional ULN, then direct bilirubin must be < 40% of total bilirubin.
    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 14 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.
  • 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). Subjects who have not required systemic treatment in the past 2 years may be eligible with approval of the medical monitor. Note: Subjects with hyper/ hypothyroidism are eligible to participate. 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 apart from 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, after treatment with curative intent.
  • 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.
  • Active infection requiring systemic therapy.
  • Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection or risk of reactivation. HBV-DNA and HCV-RNA must be undetectable. Subjects cannot be positive for HBV-DNA, HCV-RNA, hepatitis B surface antigen, or anti-hepatitis B core antibody. Note: Subjects with no prior history of hepatitis B infection who have been vaccinated against hepatitis B and who have a positive antibody against hepatitis B surface antigen test as the only evidence of prior exposure may participate in the study.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Director of Clinical Operations 240-479-2720 NCClin@NextCure.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03665285
Other Study ID Numbers  ICMJE NC318-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party NextCure, Inc.
Study Sponsor  ICMJE NextCure, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Kevin N. Heller, MD NextCure, Inc.
PRS Account NextCure, Inc.
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP