Clinical Trials /

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

NCT03665285

Description:

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

Related Conditions:
  • Breast Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Safety and Tolerability Study of NC318 in Subjects With Advanced or Metastatic Solid Tumors
  • Official Title: A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of NC318 in Subjects With Advanced or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: NC318-01
  • NCT ID: NCT03665285

Conditions

  • Advanced or Metastatic Solid Tumors
  • Head and Neck Squamous Cell Carcinoma
  • Non-Small Cell Lung Cancer
  • Ovarian Cancer
  • Triple Negative Breast Cancer

Interventions

DrugSynonymsArms
NC318NC318

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
NC318ExperimentalNC318 for injection of various dose strengths administered in 14 day dosing cycles
  • NC318

Eligibility 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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with treatment-emergent Adverse Events as assessed by CTCAE v5.0
Time Frame:up to 14 months
Safety Issue:
Description:Frequency, duration, and severity of treatment-emergent adverse events (AEs)

Secondary Outcome Measures

Measure:Disease Response as assessed by RECIST 1.1 and mRECIST
Time Frame:up to 14 months
Safety Issue:
Description: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
Measure:Maximum Plasma Concentration (Cmax) of NC318
Time Frame:14 weeks
Safety Issue:
Description:To evaluate the Maximum Plasma Concentration (Cmax) of NC318
Measure:Area Under the Curve (AUC) of NC318
Time Frame:14 weeks
Safety Issue:
Description:To evaluate the Area Under the Curve (AUC) of NC318
Measure:Half-life (t1/2) of NC318
Time Frame:14 weeks
Safety Issue:
Description:To evaluate the half-life (t1/2) of NC318

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:NextCure, Inc.

Trial Keywords

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

Last Updated

November 11, 2019