NC410 plus FOLFIRINOX with nivolumab, with or without ipilimumab, for 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

This trial tests whether adding NC410 to standard FOLFIRINOX with nivolumab (and sometimes ipilimumab) is safe and tolerable for adults with untreated metastatic pancreatic cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Academic / other)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 1 site (Baltimore, Maryland)
• Trial ID: NCT06941857 on ClinicalTrials.gov

What this trial studies

This Phase 2, single-center interventional trial combines the chemotherapy regimen FOLFIRINOX with the PD-1 inhibitor nivolumab and the investigational LAIR-2 fusion protein NC410, with an optional arm including ipilimumab. The primary focus is safety monitoring and identification of any novel toxicities from the combination. Eligible participants are adults with histologically confirmed, untreated metastatic pancreatic ductal adenocarcinoma, ECOG 0–1, measurable disease, and adequate organ function. Treatments are administered per protocol at the enrolling center and patients are followed for adverse events and treatment tolerability.

Who should consider this trial

Good fit: Adults (≥18) with untreated metastatic pancreatic ductal adenocarcinoma, ECOG performance status 0–1, measurable disease, and adequate organ and marrow function are the intended candidates.

Not a fit: Patients who have received prior systemic chemotherapy for pancreatic cancer, have poor performance status (ECOG ≥2), or significant organ dysfunction are unlikely to be eligible or to benefit.

Why it matters

Potential benefit: If successful, this combination could expand treatment options and possibly improve response rates or survival for patients with untreated metastatic pancreatic cancer.

How similar studies have performed: Immune checkpoint inhibitors alone have generally had limited success in pancreatic cancer, combinations of chemotherapy with PD-1/CTLA-4 agents have shown modest benefit to date, and NC410 represents a novel approach with limited prior clinical data.

Eligibility criteria

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.

Where this trial is running

Baltimore, Maryland

• Sidney Kimmel Comprehensive Cancer Center — Baltimore, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Katherine Bever, MD — SKCCC Johns Hopkins Medical Institution
• Study coordinator: Colleen Apostol, RN

Conditions Pancreatic Cancer; Nivolumab; Ipilimumab; NC410 fusion protein); Oxaliplatin; Irinotecan; Folinic Acid; 5-Fluorouracil