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

NCT03665285 | Completed Phase 1 Results FDA Drug

• 1 other identifier: NC318-01
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 6

Brief Summary

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

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-emergent Adverse Events as Assessed by CTCAE v5.0

  The number of participants who have had at least one TEAE during the study.

  From enrollment through up to 90 days after end of treatment, an average of 1 year

Secondary Outcomes (8)

• Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  Approximately 1 year

• Duration of Response (DoR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  Approximately 1 year

• Disease Control Rate (DCR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  Approximately 1 year

• Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  Approximately 1 year

• Overall Survival (OS)

  Approximately 1 year

Study Arms (9)

NC318 8mg

EXPERIMENTAL

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).

Drug: NC318

NC318 24mg

EXPERIMENTAL

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).

Drug: NC318

NC318 80mg

EXPERIMENTAL

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).

Drug: NC318

NC318 240mg

EXPERIMENTAL

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).

Drug: NC318

NC318 400mg

EXPERIMENTAL

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).

Drug: NC318

NC318 800mg

EXPERIMENTAL

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).

Drug: NC318

NC318 1600mg

EXPERIMENTAL

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).

Drug: NC318

Dose Expansion: 400mg Q2W

EXPERIMENTAL

Phase 2 Dose Expansion (400mg): Subjects received NC318 IV at 400mg Q2W until disease progression, withdraw of consent, or intolerable toxicity (whichever comes first).

Drug: NC318

Dose Expansion: 800mg QW

EXPERIMENTAL

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).

Drug: NC318

Interventions

NC318 DRUG

NC318 is an experimental antibody drug that may make the immune response more active against cancer.

Dose Expansion: 400mg Q2W; Dose Expansion: 800mg QW; NC318 1600mg; NC318 240mg; NC318 24mg; NC318 400mg; NC318 800mg; NC318 80mg; NC318 8mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 corticosteroids equivalent to prednisone \</= 10mg/day is allowed.

Sponsors & Collaborators

• NextCure, Inc.: lead

Study Sites (6)

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

Yale University Cancer Center

New Haven, Connecticut, 06510, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Laura and Isaac Perlmutter Cancer Center

New York, New York, 10016, United States

Location

Pennsylvania Cancer Specialists and Research Institute

Gettysburg, Pennsylvania, 17325, United States

Location

NEXT Oncology

San Antonio, Texas, 78240, United States

Location

MeSH Terms

Conditions

Lung Neoplasms; Breast Neoplasms; Squamous Cell Carcinoma of Head and Neck; Endometrial Neoplasms; Melanoma; Carcinoma, Transitional Cell; Cholangiocarcinoma; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Adenocarcinoma; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Chief Medical Officer
• Organization: NextCure, Inc.

NCClin@nextcure.com

(240) 399-4900

Study Officials

• Han Myint, MD

  NextCure, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 6, 2018
• First Posted: September 11, 2018
• Study Start: October 1, 2018
• Primary Completion: April 11, 2023
• Study Completion: April 11, 2023
• Last Updated: March 8, 2024
• Results First Posted: March 8, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)