NC410 and FOLFIRINOX in Combination With Nivolumab With or Without Ipilimumab in Patients With Untreated Metastatic Pancreatic Cancer

A Phase 2 Study of NC410 and FOLFIRINOX in Combination With Nivolumab With or Without Ipilimumab in Patients With Treatment-naïve, Metastatic Pancreatic Cancer

The purpose of this study is to evaluate safety of the treatment regimen and identify any novel toxicities.

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Oxaliplatin; Drug: Irinotecan; Drug: Folinic Acid; Drug: 5-Fluorouracil (5-FU); Drug: NC410; Drug: Nivolumab; Drug: Ipilimumab

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Colleen Apostol, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Recruiting
      • Sidney Kimmel Comprehensive Cancer Center
      • Contact: Colleen Apostol, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu
      • Principal Investigator: Katherine Bever, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1.
• Metastatic histologically or cytologically confirmed pancreatic ductal adenocarcinoma.
• Have metastatic disease
• Must not have received prior systemic treatment for pancreatic cancer.
• Have measurable disease based on RECIST 1.1.
• Patients must have adequate organ and marrow function defined by study-specified laboratory tests and procedures.
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test.
• For both Women and Men, must use acceptable form of birth control while on study.
• Must understand the study regimen, its requirements, risks and discomforts and is able and willing to sign the informed consent form in accordance with regulatory and institutional guidelines.

Exclusion Criteria:

• Have had prior chemotherapy for pancreatic cancer or prior chemotherapy within 5 years of enrollment for other cancer diagnoses.
• Has received radiotherapy for pancreatic cancer.
• Are receiving or have received any investigational agent or used an investigational device within 28 days prior to Day 1 of treatment in this study.
• Has undergone major surgery, other than diagnostic surgery (i.e. surgery done to obtain a biopsy for diagnosis or an aborted Whipple), within 28 days prior to Day 1 of treatment in this study.
• Is expected to require any other form of systemic or localized antineoplastic therapy while on study.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, or anti-Lag-3 antibodies.
• Has received a live vaccine or live-attenuated vaccine within 28 days prior to the first dose of study drug.
• Prior tissue or organ allograft regardless of need for immunosuppression, including corneal allograft.
• Has uncontrolled acute or chronic medical illness.
• Has history of central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has known additional malignancy that is progressing and requires active treatment.
• Has active autoimmune disease.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent).
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Requirement for daily supplemental oxygen.
• History of interstitial lung disease, non-infectious pneumonitis or uncontrolled lung diseases including pulmonary fibrosis, acute lung diseases, chronic obstructive pulmonary disease (COPD), asthma requiring medication, etc.
• Known history of human immunodeficiency virus (HIV).
• Active or chronic hepatitis B or hepatitis C.
• Unable to undergo venipuncture and/or tolerate venous access.
• Has known psychiatric or substance use disorder that would interfere with cooperation with the requirements of the trial.
• Pregnant or breastfeeding
• A WOCBP who has a positive urine pregnancy test within 72 hours prior to study drug initiation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1 - FOLFIRINOX/NC410/Nivolumab	Drug: Oxaliplatin; 65mg/m2 will be administered as a 120 minute IV Infusion (-10/+ 20 minutes) on day 1 of each cycle every 2 weeks. Each cycle length is 14 days. The two arms will enroll sequentially (starting with Arm 1 followed by Arm 2).; Drug: Irinotecan; 150 mg/m2 will be administered as a 90 minute IV Infusion (-10/+ 20 minutes) on day 1 of each cycle every 2 weeks. Each cycle length is 14 days. The two arms will enroll sequentially (starting with Arm 1 followed by Arm 2).; Drug: Folinic Acid; 50 mg will be administered as a 15 minute IV infusion (-5/+20 min) on day 1 of each cycle every 2 weeks. Each cycle length is 14 days. Folinic acid can be given concurrent with irinotecan. The two arms will enroll sequentially (starting with Arm 1 followed by Arm 2).; Drug: 5-Fluorouracil (5-FU); 2400 mgm2 will be administered as a continuous IV Infusion (-120/+ 120 minutes) over approximately 46 hours on day 1 of each cycle every 2 weeks. Each cycle length is 14 days. The two arms will enroll sequentially (starting with Arm 1 followed by Arm 2).; Drug: NC410; 100 mg will be administered as a 60 minute IV Infusion (-10/+ 20 minutes) on day 1 of each cycle every 2 weeks. Each cycle length is 14 days. The two arms will enroll sequentially (starting with Arm 1 followed by Arm 2).; Other Names: NextCure LAIR-2 fusion protein; Drug: Nivolumab; 400 mg will be administered as a 30 minute IV Infusion (-5/+20 minutes) once on Cycle 1 Day 1. Each cycle length is 14 days. The two arms will enroll sequentially (starting with Arm 1 followed by Arm 2).; Other Names: OPDIVO
Experimental: Arm 2 - FOLFIRINOX/NC410/Nivolumab/Ipilimumab	Drug: Oxaliplatin; 65mg/m2 will be administered as a 120 minute IV Infusion (-10/+ 20 minutes) on day 1 of each cycle every 2 weeks. Each cycle length is 14 days. The two arms will enroll sequentially (starting with Arm 1 followed by Arm 2).; Drug: Irinotecan; 150 mg/m2 will be administered as a 90 minute IV Infusion (-10/+ 20 minutes) on day 1 of each cycle every 2 weeks. Each cycle length is 14 days. The two arms will enroll sequentially (starting with Arm 1 followed by Arm 2).; Drug: Folinic Acid; 50 mg will be administered as a 15 minute IV infusion (-5/+20 min) on day 1 of each cycle every 2 weeks. Each cycle length is 14 days. Folinic acid can be given concurrent with irinotecan. The two arms will enroll sequentially (starting with Arm 1 followed by Arm 2).; Drug: 5-Fluorouracil (5-FU); 2400 mgm2 will be administered as a continuous IV Infusion (-120/+ 120 minutes) over approximately 46 hours on day 1 of each cycle every 2 weeks. Each cycle length is 14 days. The two arms will enroll sequentially (starting with Arm 1 followed by Arm 2).; Drug: NC410; 100 mg will be administered as a 60 minute IV Infusion (-10/+ 20 minutes) on day 1 of each cycle every 2 weeks. Each cycle length is 14 days. The two arms will enroll sequentially (starting with Arm 1 followed by Arm 2).; Other Names: NextCure LAIR-2 fusion protein; Drug: Nivolumab; 400 mg will be administered as a 30 minute IV Infusion (-5/+20 minutes) once on Cycle 1 Day 1. Each cycle length is 14 days. The two arms will enroll sequentially (starting with Arm 1 followed by Arm 2).; Other Names: OPDIVO; Drug: Ipilimumab; 50 mg will be administered as a 30 minute IV Infusion (-5/+20 minutes) once on Cycle 1 Day 1. Each cycle length is 14 days. The two arms will enroll sequentially (starting with Arm 1 followed by Arm 2).; Other Names: YERVOY

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants experiencing unexpected toxicities. Unexpected toxicities are toxicities related to the study drug required treatment discontinuation.	When calculating the incidence of Adverse Events (AEs), each AE (as defined by NCI CTCAE v5.0) will be counted only once for a given subject.	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression- Free Survival (PFS)	PFS is defined as the number of months from the date of first dose to disease progression (PD as assessed using RECIST 1.1 criteria) or death due to any cause. PFS will be censored at the date of the last scan for subjects without documentation of disease progression at the time of analysis. PFS will be censored at time of first dose for patients that do not have a follow-up scan. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30percent decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20percent increase in sum of diameters of target lesions, Stable Disease (SD) is <30percent decrease or <20percent increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.	4 years
Response Rate (ORR)	ORR is defined as the number of subjects with PR or CR according to RECIST 1.1. Subjects who discontinue due to toxicity or clinical progression prior to post-baseline tumor assessments will be considered as non-responders. CR = disappearance of all target lesions, PR is =>30percent decrease in sum of diameters of target lesions, progressive disease (PD) is >20percent increase in sum of diameters of target lesions, stable disease (SD) is <30percent decrease or <20percent increase in sum of diameters of target lesions.	4 years
Disease Control Rate (DCR)	DCR is defined as the number of subjects achieving stable disease or better (SD, PR or CR) according to RECIST 1.1. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30percent decrease in sum of diameters of target lesion, Stable Disease (SD) is <30percent decrease or <20percent increase in sum of diameters of target lesions.	4 years
Overall Survival (OS)	OS is defined as the number of months from the date of first dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.	4 years

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: Lustgarten Foundation; NextCure, Inc.
• Investigators: Principal Investigator: Katherine Bever, MD, SKCCC Johns Hopkins Medical Institution

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: April 16, 2025
• First Submitted That Met QC Criteria: April 16, 2025
• First Posted (Actual): April 24, 2025

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Nivolumab; Carcinoma; Immunotherapy; Pancreatic Cancer; Ipilimumab; Pancreas; Irinotecan; Oxaliplatin; 5-Fluorouracil; Metastatic Pancreatic Cancer; Pancreatic Ductal Adenocarcinoma (PDAC); Folinic Acid; Folfirinox; Anti-PD-1 (anti-check point inhibitor); PD-L1 (check point inhibitor); NC410 (NextCure LAIR-2 (Leukocyte-Associated Immunoglobulin-like Receptor-2) fusion protein); Anti-CTLA-4 (anti-cytotoxic T-lymphocyte-associated antigen 4)
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms, Glandular and Epithelial; Carcinoma; Pancreatic Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Camptothecin; Alkaloids; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Oxaliplatin; Nivolumab; Irinotecan; Ipilimumab; Fluorouracil; Leucovorin
• Other Study ID Numbers: J2541; IRB00486324 (Other Identifier: Johns Hopkins Medical Institution)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No