A Safety and Tolerability Study of NC410 in Subjects With Advanced or Metastatic Solid Tumors

Ovarian Cancer Clinical Trial

Official title:

A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of NC410 in Subjects With Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04408599
• Other study ID #: NC410-01
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: June 10, 2020
• Est. completion date: July 7, 2023

Study information

• Verified date: January 2024
• Source: NextCure, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This research study is studying a new drug, NC410, as a possible treatment for advanced or metastatic solid tumors.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 46
• Est. completion date: July 7, 2023
• Est. primary completion date: July 7, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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.

• Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.

• 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 NC410-01 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.

Related Conditions & MeSH terms

• Advanced or Metastatic Solid Tumors
• Colo-rectal Cancer
• Gastric Cancer
• Ovarian Cancer
• Ovarian Neoplasms
• Rectal Neoplasms
• Stomach Neoplasms

Intervention

Drug:
• NC410
NC410 is an experimental antibody drug that may make the immune response more active against cancer

Locations

Country	Name	City	State
United States	NIH National Cancer Institute (NCI)	Bethesda	Maryland
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	UT MD Anderson Cancer Center	Houston	Texas
United States	NYU Langone Health	New York	New York
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
NextCure, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0	Frequency, duration, and severity of treatment-emergent adverse events (AEs)	From enrollment through up to 90 days after end of treatment, an average of 1 year
Primary	Define a maximum tolerated dose (MTD) or pharmacologically active dose (PAD)	A 3 + 3 design will be utilized to determine the MTD of NC410	28 days
Secondary	Objective Response Rate per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	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	Approximately 1 year
Secondary	Duration of Response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Modified Response Evaluation Criteria in Solid Tumors	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 or Modified Response Evaluation Criteria in Solid Tumors to the first documented progressive disease or death due to any cause, whichever occurs first.	Approximately 1 year
Secondary	Disease Control Rate per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	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.	Approximately 1 year
Secondary	Maximum Plasma Concentration (Cmax) of NC410	To evaluate the Maximum Plasma Concentration (Cmax) of NC410	Days 1, 2, 3 and 8 of Cycles 1 and 5 and Day 1 of Cycles 2, 3, 6, 7, 9, 11, 17, and 23. Each cycle is 14 days in duration.
Secondary	Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Modified Response Evaluation Criteria in Solid Tumors	To evaluate progression-free survival (PFS), defined as the time from the first dose of NC410 to the first occurrence of documented progressive disease or death due to any cause, whichever occurs first.	Approximately 1 year
Secondary	Overall survival (OS) as assessed by time of death	To evaluate overall survival (OS), defined as the time from the first dose of NC410 to death due to any cause.	Approximately 1 year
Secondary	Area Under the Curve (AUC) of NC410	To evaluate the Area Under the Curve (AUC) of NC410	Days 1, 2, 3 and 8 of Cycles 1 and 5 and Day 1 of Cycles 2, 3, 6, 7, 9, 11, 17, and 23. Each cycle is 14 days in duration.
Secondary	Half-life (t1/2) of NC410	To evaluate the half-life (t1/2) of NC410	Days 1, 2, 3 and 8 of Cycles 1 and 5 and Day 1 of Cycles 2, 3, 6, 7, 9, 11, 17, and 23. Each cycle is 14 days in duration.