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

Phase 1

Completed

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

Interventions: Drug: NC318

Registration Number: NCT03665285

Lead Sponsor: NextCure, Inc.

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 109

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
NC318 240mg	NC318	Phase 1 Dose Escalation/Safety Expansion (Cohort 3): Subjects received NC318 IV at 240mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
NC318 80mg	NC318	Phase 1 Dose Escalation/Safety Expansion (Cohort 2): Subjects received NC318 IV at 80mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
NC318 1600mg	NC318	Phase 1 Dose Escalation (Cohort 6): Subjects received NC318 IV at 1600mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
NC318 8mg	NC318	Phase 1 Dose Escalation (Cohort -1): Subjects received NC318 IV at 8mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
NC318 400mg	NC318	Phase 1 Dose Escalation/Safety Expansion (Cohort 4): Subjects received NC318 IV at 400mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
Dose Expansion: 400mg Q2W	NC318	Phase 2 Dose Expansion (400mg): Subjects received NC318 IV at 400mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
Dose Expansion: 800mg QW	NC318	Phase 2 Dose Expansion (800mg): Subjects received NC318 IV at 800mg QW for 8 weeks, then Q2W thereafter until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
NC318 800mg	NC318	Phase 1 Dose Escalation (Cohort 5): Subjects received NC318 IV at 800mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).
NC318 24mg	NC318	Phase 1 Dose Escalation (Cohort 1): Subjects received NC318 IV at 24mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v5.0	From enrollment through up to 90 days after end of treatment, an average of 1 year	The number of participants who have had at least one TEAE during the study.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Approximately 1 year	To assess antitumor activity/efficacy by evaluating objective response rate (ORR), defined as the percentage of participants who experienced a complete response (CR; disappearance of all target lesions) or a partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Duration of Response (DoR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Approximately 1 year	To assess antitumor activity/efficacy by evaluating duration of response (DoR), defined as the time from the first documented complete response or partial response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 to the first documented progressive disease or death due to any cause, whichever occurs first. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions.
Area Under the Curve (AUC) of NC318	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.	To evaluate the Area Under the Curve (AUC) of NC318
Half-life (t1/2) of NC318	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.	To evaluate the half-life (t1/2) of NC318
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Approximately 1 year	To evaluate progression-free survival (PFS), defined as the time from the first dose of NC318 to the first occurrence of documented progressive disease or death due to any cause, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Disease Control Rate (DCR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Approximately 1 year	To assess antitumor activity/efficacy by evaluating disease control rate (DCR), defined as the proportion of participants in whom a documented complete response, partial response, or stable disease is observed as the best overall response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Overall Survival (OS)	Approximately 1 year	To evaluate overall survival (OS), defined as the time from the first dose of NC318 to death due to any cause.
Maximum Plasma Concentration (Cmax) of NC318	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.	To evaluate the Maximum Plasma Concentration (Cmax) of NC318

Trial Locations

Locations (6): John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸
Hackensack, New Jersey, United States
The Angeles Clinic and Research Institute
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Los Angeles, California, United States
NEXT Oncology
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San Antonio, Texas, United States
Yale University Cancer Center
🇺🇸
New Haven, Connecticut, United States
Laura and Isaac Perlmutter Cancer Center
🇺🇸
New York, New York, United States
Pennsylvania Cancer Specialists and Research Institute
🇺🇸
Gettysburg, Pennsylvania, United States