Clinical trial NCT03665285: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced or Metastatic Solid Tumors
Lung Cancer
Breast Cancer
Head and Neck Squamous Cell Carcinoma
Endometrial Cancer
Melanoma
CRC
Urothelial Carcinoma
Cholangiocarcinoma
Keywords: Advanced Cancer
Metastatic Cancer
NC318
Immunotherapy
PD-L1
Dose Escalation
Biomarker
PK
Cohort Expansion
Solid Tumor
Lead sponsor: NextCure, Inc.
Sponsor class: INDUSTRY
First posted: 2018-09-11
Enrollment: 109
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Phase 1 will utilize a 3 + 3 design to explore escalating dose levels. Phase 2 Dose Expansion will further evaluate the safety, tolerability, preliminary efficacy, and PK/PD activity of NC318 at the RP2D utilizing a Simon 2-stage design.
Primary purpose: TREATMENT

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


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.
* Subjects with advanced unresectable and/or metastatic solid tumors.
* 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.
* Able to provide pretreatment tumor tissue sample at Screening.
* Subjects of childbearing potential (defined as female subjects who have not undergone surgical sterilization with a hysterectomy and/or bilateral oophorectomy and are not postmenopausal, defined as ≥ 12 months of amenorrhea not caused by reversible conditions, diseases, or medications) and non-sterilized male subjects 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.

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 or 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 corticosteroids equivalent to prednisone \</= 10mg/day is allowed.
  5. ≤ 28 days or 5 half-lives (whichever is longer) before the first dose for all other investigational study drugs or devices.
  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.
* 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 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.
* Has a history of (non-infectious) pneumonitis / interstitial lung disease that required steroids or has current pneumonitis / 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 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.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v5.0
timeFrame: From enrollment through up to 90 days after end of treatment, an average of 1 year
Secondary outcomes:
measure: Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
timeFrame: Approximately 1 year
measure: Duration of Response (DoR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
timeFrame: Approximately 1 year
measure: Disease Control Rate (DCR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
timeFrame: Approximately 1 year
measure: Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
timeFrame: Approximately 1 year
measure: Overall Survival (OS)
timeFrame: Approximately 1 year
measure: Maximum Plasma Concentration (Cmax) of NC318
timeFrame: Days 1, 2, and 3 of Cycles 1 and 5 and Day 1 of Cycles 2, 3, 6, 9, 13, 17, and 21. Each cycle is 7 days during Cycles 1-8 and 14 days thereafter.
measure: Area Under the Curve (AUC) of NC318
timeFrame: Days 1, 2, and 3 of Cycles 1 and 5 and Day 1 of Cycles 2, 3, 6, 9, 13, 17, and 21. Each cycle is 7 days during Cycles 1-8 and 14 days thereafter.
measure: Half-life (t1/2) of NC318
timeFrame: Days 1, 2, and 3 of Cycles 1 and 5 and Day 1 of Cycles 2, 3, 6, 9, 13, 17, and 21. Each cycle is 7 days during Cycles 1-8 and 14 days thereafter.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute
state: California
city: New Haven
country: United States
facility: Yale University Cancer Center
state: Connecticut
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center
state: New York
city: Gettysburg
country: United States
facility: Pennsylvania Cancer Specialists and Research Institute
state: Pennsylvania
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
Study officials:
affiliation: NextCure, Inc.
name: Han Myint, MD
role: STUDY_DIRECTOR
References: