NC410 + FOLFIRINOX + Nivolumab for Pancreatic Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Immunosuppressants, Steroids, Antineoplastics, Vaccines

Disqualifiers: Autoimmune disease, CNS metastases, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4 years

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of cancer treatments for individuals with metastatic pancreatic cancer. Researchers aim to assess the safety of these treatments and identify any unexpected side effects. Participants will receive a mix of drugs, including FOLFIRINOX, NC410 (an experimental treatment), and Nivolumab, with some also receiving Ipilimumab. Ideal candidates have confirmed metastatic pancreatic cancer, have not undergone prior treatment for this cancer, and can tolerate the study drugs. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on chronic systemic steroid therapy or require daily supplemental oxygen, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that adding NC410 to FOLFIRINOX and Nivolumab might be a safe treatment option for patients with advanced pancreatic cancer. However, earlier studies found a higher risk of serious side effects when these drugs are combined. About 54% of patients experienced severe side effects, which are more serious than mild or moderate ones.

When Ipilimumab is also added, no new safety issues have been reported, but the combination did not demonstrate strong cancer-fighting effects in some studies. Overall, these treatments have been tested in people before, providing some evidence of safety, though serious side effects can still occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for pancreatic cancer because they combine innovative strategies to enhance the body's immune response against cancer cells. Unlike the standard of care, which typically involves chemotherapy like FOLFIRINOX alone, this trial explores the addition of NC410 and Nivolumab, with some patients also receiving Ipilimumab. NC410 works by targeting a unique protein that helps cancer evade the immune system, potentially making tumors more susceptible to attack. Nivolumab and Ipilimumab are immunotherapies that further boost the immune system's ability to fight cancer. By combining these treatments, researchers hope to improve outcomes for patients battling this notoriously challenging cancer.

What evidence suggests that this trial's treatments could be effective for pancreatic cancer?

Research has shown that combining NC410, FOLFIRINOX, and Nivolumab holds promise for treating pancreatic cancer. In this trial, some participants will receive this combination. Nivolumab with FOLFIRINOX has proven manageable, with results aligning with past studies. Early evidence suggests NC410 enhances the effectiveness of these drugs. Another group in this trial will receive an additional treatment with Ipilimumab. Adding Ipilimumab has successfully improved long-term survival in other cancers, such as melanoma. However, this combination can lead to more severe side effects, with over half of the patients experiencing serious health issues. ^{1 2 3 4 5}

Who Is on the Research Team?

Katherine Bever, MD

Principal Investigator

SKCCC Johns Hopkins Medical Institution

Are You a Good Fit for This Trial?

This trial is for adults with untreated metastatic pancreatic cancer who have measurable disease and are in good physical condition (ECOG 0-1). They must not be pregnant, agree to use birth control, and have proper organ/marrow function. Excluded are those with autoimmune diseases, HIV, other active cancers needing treatment, recent major surgery or live vaccines, prior specific cancer treatments or immunotherapies.

Inclusion Criteria

Have measurable disease based on RECIST 1.1

Women of childbearing potential (WOCBP) must have a negative serum pregnancy test

Must use acceptable form of birth control while on study

Exclusion Criteria

Has active autoimmune disease

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 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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive FOLFIRINOX, NC410, and Nivolumab with or without Ipilimumab to evaluate safety and identify novel toxicities

4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

What Are the Treatments Tested in This Trial?

Interventions

• FOLFIRINOX
• Ipilimumab
• NC410
• Nivolumab

Trial Overview The study tests the safety of a combination therapy for pancreatic cancer: NC410 plus FOLFIRINOX regimen (Oxaliplatin, Irinotecan, Folinic Acid, 5-FU) alongside Nivolumab with/without Ipilimumab. It aims to identify any new side effects from this treatment mix.

How Is the Trial Designed?

Group I: Arm 2 - FOLFIRINOX/NC410/Nivolumab/Ipilimumab Experimental Treatment 7 Interventions

Group II: Arm 1 - FOLFIRINOX/NC410/Nivolumab Experimental Treatment 6 Interventions

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

NextCure, Inc.

Industry Sponsor

Trials

8

Recruited

660+

Lustgarten Foundation

Collaborator

Trials

27

Recruited

5,500+

Published Research Related to This Trial

In a case series of seven patients treated with immune checkpoint inhibitors (ICIs), two developed diabetic ketoacidosis (DKA) and five experienced pancreatitis, highlighting the potential for serious pancreatic adverse events associated with ICI therapy.

Pancreatitis was often asymptomatic and could be managed effectively by holding the ICI treatment and administering steroids, with some patients able to safely resume ICI therapy after recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancreatic adverse events in patients treated with immune checkpoint inhibitors. Hana, C., Rehman, T., Park, K., et al.[2023]

In a meta-analysis of 2,946 cancer patients, the combination therapy of nivolumab and ipilimumab was found to significantly increase the risk of immune-related adverse events (irAEs) compared to nivolumab alone.

Patients receiving the combination therapy experienced higher rates of various irAEs, including skin reactions, gastrointestinal issues, and liver enzyme elevation, indicating a need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of immune-related adverse events associated with ipilimumab-plus-nivolumab and nivolumab therapy in cancer patients. Zhou, S., Khanal, S., Zhang, H.[2022]

In a phase 2 trial involving 142 patients with untreated advanced melanoma, the combination of nivolumab and ipilimumab resulted in a 2-year overall survival rate of 63.8%, compared to 53.6% for those receiving ipilimumab alone, suggesting improved survival outcomes with the combination therapy.

However, the combination treatment was associated with a higher incidence of severe side effects, with 54% of patients experiencing grade 3-4 adverse events compared to 20% in the ipilimumab-only group, indicating a trade-off between efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Hodi, FS., Chesney, J., Pavlick, AC., et al.[2022]

Two melanoma patients experienced rare neurological immune-related adverse events (irAEs) after treatment with ipilimumab, including meningoencephalomyelitis and acute inflammatory demyelinating polyneuropathy (AIDP).

Both patients responded well to treatment with immunosuppressive therapies, highlighting the importance of early recognition and intervention for neurological irAEs to prevent long-term complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurologic immune-related adverse events associated with adjuvant ipilimumab: report of two cases. Garcia, CA., El-Ali, A., Rath, TJ., et al.[2019]

A study analyzing 70,330 adverse events reported to the FDA found that immune checkpoint inhibitors (ICIs) significantly increase the risk of gastrointestinal (GI) toxicities, particularly colitis, hepatobiliary disorders, and pancreatitis, with colitis showing the highest reporting odds ratio of 17.2.

The risk of these GI adverse events was notably higher with anti-CTLA-4 treatments compared to anti-PD-1 and anti-PD-L1 therapies, and factors such as female gender and polytherapy were identified as strong risk factors for these complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Common Immune-Related Adverse Events of Immune Checkpoint Inhibitors in the Gastrointestinal System: A Study Based on the US Food and Drug Administration Adverse Event Reporting System. Bai, X., Jiang, S., Zhou, Y., et al.[2021]

Modified-FOLFIRINOX (mFOLFIRINOX) significantly improves safety and tolerability for Chinese patients with locally advanced pancreatic cancer (LAPC), with a response rate of 37.1% and common severe side effects including neutropenia and anemia.

Patients with LAPC who received neoadjuvant therapy with mFOLFIRINOX and subsequently underwent surgery had a median overall survival of 27.7 months, which is significantly better than the 8.9 months seen in patients who had upfront surgery without prior chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Modified-FOLFIRINOX-Regimen-Based Neoadjuvant Therapy with Outcomes of Locally Advanced Pancreatic Cancer in Chinese Population. Li, X., Guo, C., Li, Q., et al.[2023]

In a study of 342 patients with metastatic pancreatic cancer, the FOLFIRINOX chemotherapy regimen significantly improved overall survival (11.1 months) compared to gemcitabine (6.8 months), indicating it is a more effective first-line treatment option.

While FOLFIRINOX showed a higher objective response rate (31.6% vs. 9.4% for gemcitabine), it also resulted in more adverse events, including a 5.4% incidence of febrile neutropenia, highlighting the need to balance efficacy with safety in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. Conroy, T., Desseigne, F., Ychou, M., et al.[2023]

The combination of ipilimumab and gemcitabine was found to be safe and tolerable for treating advanced pancreatic ductal adenocarcinoma (PDAC), with a maximum tolerated dose established at ipilimumab 3 mg/kg and gemcitabine 1,000 mg/m2.

Despite the safety of the regimen, the overall response rate was only 14%, indicating that adding ipilimumab does not significantly enhance the effectiveness compared to gemcitabine alone in advanced PDAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab and Gemcitabine for Advanced Pancreatic Cancer: A Phase Ib Study. Kamath, SD., Kalyan, A., Kircher, S., et al.[2022]

In a study of 84 patients with refractory metastatic pancreatic cancer, the combination of stereotactic body radiotherapy (SBRT) with nivolumab and ipilimumab showed a clinical benefit rate of 37.2%, indicating a significant improvement compared to 17.1% for SBRT with nivolumab alone.

The treatment was associated with a manageable safety profile, with 24.4% of patients experiencing grade 3 or higher adverse events in the SBRT/nivolumab group and 30.2% in the SBRT/nivolumab/ipilimumab group, suggesting that this combination therapy may be a viable option for patients despite the unknown contribution of SBRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II Study of Nivolumab With or Without Ipilimumab Combined With Stereotactic Body Radiotherapy for Refractory Metastatic Pancreatic Cancer (CheckPAC). Chen, IM., Johansen, JS., Theile, S., et al.[2023]

Neoadjuvant FOLFIRINOX treatment in patients with borderline resectable pancreatic cancer (BRPC) resulted in a median overall survival of 22.2 months and a high resection rate of 67.8%, indicating its potential effectiveness in this patient group.

The treatment was associated with manageable adverse events, with the most common being neutropenia, diarrhea, and fatigue, but no deaths were reported due to FOLFIRINOX, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant FOLFIRINOX in Patients With Borderline Resectable Pancreatic Cancer: A Systematic Review and Patient-Level Meta-Analysis. Janssen, QP., Buettner, S., Suker, M., et al.[2021]

Ipilimumab, an anti-CTLA-4 antibody, has been shown to improve survival in patients with unresectable or metastatic melanoma, with a standard dosing of 3 mg/kg every 3 weeks for a total of 4 doses.

While ipilimumab can cause immune-related adverse events in 15% of patients, most are mild and manageable; however, high-grade events can be serious and require careful monitoring and treatment with corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab for advanced melanoma: a pharmacologic perspective. Trinh, VA., Hagen, B.[2021]

In a phase 3 trial involving 1150 patients with advanced non-small-cell lung cancer (NSCLC), the combination of nivolumab and ipilimumab with two cycles of chemotherapy significantly improved overall survival compared to chemotherapy alone, with a median survival of 15.6 months versus 10.9 months.

The treatment regimen showed a favorable safety profile, with serious treatment-related adverse events occurring in 30% of the experimental group compared to 18% in the control group, indicating that the benefits of the combination therapy outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Paz-Ares, L., Ciuleanu, TE., Cobo, M., et al.[2021]

In a phase 1 trial involving 53 patients with advanced melanoma, the combination of nivolumab and ipilimumab resulted in a 40% objective response rate, with 65% of patients showing clinical activity, indicating significant effectiveness in tumor reduction.

The concurrent treatment had a manageable safety profile, with 53% of patients experiencing grade 3 or 4 adverse events, which were similar to those seen with monotherapy and generally reversible, suggesting that this combination therapy is a viable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab in advanced melanoma. Wolchok, JD., Kluger, H., Callahan, MK., et al.[2022]

In the Asian subpopulation with advanced non-small cell lung cancer (NSCLC) and PD-L1 expression ≥1%, patients treated with nivolumab plus ipilimumab showed significantly improved overall survival (OS) and progression-free survival (PFS) compared to those receiving chemotherapy, with a 3-year OS rate of 53% versus 37%.

The safety profile of nivolumab plus ipilimumab was manageable, with grade 3-4 treatment-related adverse events occurring in 40% of patients, similar to the 36% in the chemotherapy group, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients. O'Byrne, KJ., Lee, KH., Kim, SW., et al.[2022]

In a pooled analysis of 1332 patients with advanced non-small-cell lung cancer (NSCLC), the combination of nivolumab and ipilimumab showed a median overall survival (OS) of 18.6 months and a 3-year OS rate of 35%, indicating significant long-term survival benefits compared to traditional chemotherapy.

The study found that patients who responded to treatment at 6 months had markedly better survival rates, with a 3-year OS of 66% for responders, highlighting the importance of early response in predicting long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. Borghaei, H., Ciuleanu, TE., Lee, JS., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06941857

Study Details | NCT06941857 | NC410 and FOLFIRINOX in ... A Phase 2 Study of NC410 and FOLFIRINOX in Combination With Nivolumab With or Without Ipilimumab in Patients With Treatment-naïve, Metastatic Pancreatic Cancer.

2. withpower.com withpower.com/trial/phase-2-pancreatic-neoplasms-5-2025-dca5c

NC410 + FOLFIRINOX + Nivolumab for Pancreatic Cancer However, the combination treatment was associated with a higher incidence of severe side effects, with 54% of patients experiencing grade 3-4 adverse events ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11524122/

A Phase 2 study of nivolumab in combination with modified ... Nivolumab+mFOLFIRINOX was tolerable in patients with metastatic pancreatic cancer. ORR and survival were comparable to previously reported data.

4. trialx.com trialx.com/clinical-trials/listings/300709/nc410-and-folfirinox-in-combination-with-nivolumab-with-or-without-ipilimumab-in-patients-with-untreated-metastatic-pancreatic-cancer/

NC410 and FOLFIRINOX in Combination With Nivolumab ... Overview. The purpose of this study is to evaluate safety of the treatment regimen and identify any novel toxicities.

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-05386

NC410 in Combination with Nivolumab and FOLFIRINOX ... This phase II trial tests the safety and effectiveness of NC410 in combination with nivolumab and fluorouracil, irinotecan, leucovorin and oxaliplatin ...