Brief Title: NC318 in Subjects With Advanced or Metastatic Solid Tumors

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Number of participants with treatment-emergent Adverse Events as assessed by CTCAE v5.0

Primary Outcome 1 - Timeframe: up to 14 months

Primary Outcome 2 - Measure: Define a maximum tolerated dose (MTD) or pharmacologically active dose (PAD)

Primary Outcome 2 - Timeframe: 28 days

CONDITION

• Advanced or Metastatic Solid Tumors
• Lung Cancer
• Breast Cancer
• Head and Neck Squamous Cell Carcinoma
• Endometrial Cancer
• Melanoma
• CRC
• Urothelial Carcinoma
• Cholangiocarcinoma

ELIGIBILITY

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:
Absolute neutrophil count < 1.5 × 10^9/L - Platelets < 100 × 10^9/L - Hemoglobin < 9 g/dL or < 5.6 mmol/L - Serum creatinine > 1.5 × institutional upper limit of normal (ULN)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2.5 × ULN

- Total bilirubin > 1.5 × ULN.

- 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:
≤ 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.

- ≤ 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).

- ≤ 28 days for a prior monoclonal antibody used for anticancer therapy except for denosumab.

- ≤ 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.

- ≤ 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.

- ≤ 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.

- 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 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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Han Myint, MD

Role: Study Director

Affiliation: NextCure, Inc.

Overall Contact

Name: Han Myint, MD

Phone: 240-763-0535, (240) 399-4900

Email: NCClin@NextCure.com, NelsonM@NextCure.com

LOCATION