Nivolumab + Ipilimumab + Radiation for Pancreatic Cancer

Not currently recruiting at 2 trial locations

Overseen By Theodore S Hong, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: Immunosuppressants, Anti-CTLA-4

Disqualifiers: Autoimmune disease, Active infection, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination to evaluate its effectiveness for a specific type of pancreatic cancer that resists traditional treatments. The treatment includes two drugs, ipilimumab (Yervoy) and nivolumab (Opdivo), along with radiation therapy. It targets individuals with this particular form of metastatic pancreatic cancer who have already tried at least one other treatment. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on corticosteroids or other immunosuppressive medications, you may need to adjust your dosage or stop them 14 days before starting the trial, unless they are at a stable, low dose.

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

Research has shown that the combination of nivolumab and ipilimumab with radiation therapy has been tested for safety. In earlier studies, this combination did not cause unexpected side effects, meaning participants experienced no surprises in their bodily reactions. Most patients tolerated the treatments well, without serious problems.

Although this combination did not prove effective in shrinking tumors in these studies, the absence of unexpected safety issues is a positive sign for potential trial participants. Safety remains a top priority in clinical trials, and these results suggest the treatment is generally safe for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Nivolumab and Ipilimumab with radiation for pancreatic cancer because it combines cutting-edge immunotherapy with traditional radiation. Unlike most treatments that focus solely on chemotherapy, this approach uses Nivolumab and Ipilimumab to boost the immune system, helping it recognize and attack cancer cells more effectively. Additionally, combining these immune-boosting drugs with radiation can potentially enhance the overall treatment effect, aiming to improve outcomes for patients where traditional methods have limited success. This innovative combination could offer a new hope for tackling a notoriously tough cancer.

What evidence suggests that the combination of nivolumab, ipilimumab, and radiation therapy could be effective for pancreatic cancer?

In this trial, participants will receive a combination of the drugs nivolumab and ipilimumab with radiation therapy. Research has shown that this combination yields promising results for treating pancreatic cancer. One study found that it helped shrink tumors in patients with advanced pancreatic cancer. These treatments enhance the immune system's ability to identify and attack cancer cells. Although some studies did not demonstrate clear tumor shrinkage, the combination remained safe and feasible. This suggests potential benefits, particularly in advanced cases where traditional chemotherapy proves less effective. ^{2 4 5 6 7}

Who Is on the Research Team?

Theodore S Hong, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults over 18 with metastatic MSS pancreatic cancer who have had at least one prior chemotherapy treatment. They must be in good health otherwise, with proper organ and marrow function, and a life expectancy of more than 3 months. Participants need to have tumors suitable for radiation therapy and measurable disease outside the radiation field.

Inclusion Criteria

My cancer has worsened after at least one chemotherapy treatment.

My organ and bone marrow functions are normal as per recent tests.

I can do most of my daily activities without help.

Exclusion Criteria

I do not have any serious illnesses or social situations that would stop me from following the study's requirements.

Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 5 months for woman and 7 months for men, after the last dose of trial treatment

You have had a serious allergic reaction to any type of monoclonal antibody in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nivolumab and Ipilimumab with Radiation Therapy. Nivolumab is administered every 2 weeks, Ipilimumab on day 1 of each 6-week cycle, and Radiation during week 1 of cycle 1.

24 weeks

Nivolumab every 2 weeks, Ipilimumab every 6 weeks, Radiation during week 1

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab
• Radiation Therapy

Trial Overview The study tests a combination of two immunotherapy drugs, Nivolumab and Ipilimumab, along with Radiation Therapy on patients with microsatellite stable (MSS) pancreatic cancer to see how effective this trio is against the disease.

How Is the Trial Designed?

Group I: Nivolumab + Ipilimumab + Radiation Experimental Treatment 3 Interventions

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits, (Study cycles are 6 weeks.) * Nivolumab via iv, at predetermined dose every 2 weeks for duration of study. * Ipilimumab via iv at a predetermined dose on day 1 of 4 study cycles. * Radiation treatments will be administered every other weekday or 2 days during week 1 of cycle 1.

Ipilimumab is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

In a phase 1 trial with 13 patients suffering from metastatic melanoma, the combination of ipilimumab and high-dose radiation therapy was found to be feasible and safe, with 25% of patients experiencing grade 3 or 4 adverse events.

Local control of the treated lesions was achieved in 11 out of 12 patients, and while only 3 patients showed clinical benefit in non-irradiated lesions, the results suggest that early radiation therapy may enhance the effectiveness of ipilimumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Dose Escalation Trial of Ipilimumab and Stereotactic Body Radiation Therapy in Metastatic Melanoma. Sundahl, N., De Wolf, K., Kruse, V., et al.[2019]

In a phase 2 trial involving 147 patients with post-operative locally recurrent pancreatic cancer, combining high-dose stereotactic body radiation therapy (SBRT) with pembrolizumab and trametinib showed a significant improvement in progression-free survival (PFS) compared to gemcitabine, particularly in patients receiving higher radiation doses (BED10 ≥65Gy).

Although the combination treatment did not significantly extend overall survival (OS) compared to gemcitabine, the results suggest that further research is needed to explore the potential synergy of high-dose SBRT with immunotherapy and targeted therapy in larger phase 3 trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of stereotactic body radiotherapy dose escalation plus pembrolizumab and trametinib versus stereotactic body radiotherapy dose escalation plus gemcitabine for locally recurrent pancreatic cancer after surgical resection on survival outcomes: A secondary analysis of an open-label, randomised, controlled, phase 2 trial. Zhu, X., Liu, W., Cao, Y., et al.[2022]

In a phase II trial involving 65 patients with metastatic microsatellite stable colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC), combining radiation with immune checkpoint inhibitors ipilimumab and nivolumab achieved a disease control rate of 25% for CRC and 20% for PDAC, indicating some effectiveness in these challenging cancers.

The study found that patients who experienced disease control had higher levels of natural killer (NK) cells and expression of HERVK repeat RNA, suggesting that these immune factors may play a role in the response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy enhances immunotherapy response in microsatellite stable colorectal and pancreatic adenocarcinoma in a phase II trial. Parikh, AR., Szabolcs, A., Allen, JN., et al.[2023]

In a phase 2 study involving 26 patients with refractory pancreatic cancer, the combination of ipilimumab, nivolumab, tocilizumab, and stereotactic body radiotherapy (SBRT) did not result in any objective responses, indicating limited efficacy for this treatment regimen.

While 19% of patients achieved stable disease, the median overall survival was only 5.3 months, and 73% experienced treatment-related adverse events, highlighting safety concerns associated with this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of ipilimumab, nivolumab, and tocilizumab combined with stereotactic body radiotherapy in patients with refractory pancreatic cancer (TRIPLE-R). Chen, IM., Donia, M., Chamberlain, CA., et al.[2023]

Irreversible electroporation (IRE) combined with nivolumab shows a promising safety profile, as no dose-limiting toxicities were observed in a phase 1b clinical trial involving 10 patients, with a median follow-up of 12 months.

The combination therapy resulted in a mean time to progression of 6.3 months and a median overall survival of 18.0 months, suggesting potential efficacy in treating locally advanced pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1b trial of concurrent immunotherapy and irreversible electroporation in the treatment of locally advanced pancreatic adenocarcinoma. O'Neill, C., Hayat, T., Hamm, J., et al.[2023]

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 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]

Two cases of patients with multiple in-transit metastatic melanomas were successfully treated using intensity-modulated radiotherapy (IMRT) combined with immune checkpoint inhibitors ipilimumab or nivolumab.

The combination of IMRT and immune checkpoint inhibitors suggests a potential enhancement of antitumor effects, indicating a promising approach for improving treatment outcomes in melanoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of multiple in-transit melanomas on the leg with intensity-modulated radiotherapy and immune checkpoint inhibitors: Report of two cases. Fujimura, T., Kambayashi, Y., Furudate, S., et al.[2018]

Gene expression profiling in 162 advanced melanoma patients identified potential biomarkers associated with gastrointestinal immune-related adverse events (GI irAEs) during ipilimumab treatment, particularly markers related to neutrophil activation like CD177 and CEACAM1.

While a set of biomarkers was found to correlate with the occurrence of GI irAEs, their low sensitivity means they cannot reliably predict which patients will experience these adverse effects, indicating a need for further research in larger cohorts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene expression profiling of whole blood in ipilimumab-treated patients for identification of potential biomarkers of immune-related gastrointestinal adverse events. Shahabi, V., Berman, D., Chasalow, SD., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.4168

Phase 1/2 study of nivolumab and ipilimumab combined ... Background: This phase 1/2 study (NCT04247165) evaluated the safety and efficacy of combining nivolumab, ipilimumab, gemcitabine, ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40475164/

A phase II study of nivolumab, ipilimumab, and radiation in ... Combined ipilimumab, nivolumab, influenza vaccine, and SBRT in patients with PC was feasible but did not lead to objective responses.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04247165

Study Details | NCT04247165 | Nivolumab, Ipilimumab and ... Pancreatic ductal adenocarcinoma (PDAC) remains a dreadful disease due to its often advanced stage at diagnosis and poor sensitivity to chemotherapy.

4. cancernetwork.com cancernetwork.com/view/sbrt-plus-nivolumab-ipilimumab-yields-meaningful-activity-in-metastatic-pancreatic-cancer

SBRT Plus Nivolumab/Ipilimumab Yields Meaningful ... Treatment with stereotactic body radiotherapy (SBRT) plus nivolumab (Opdivo) and ipilimumab (Yervoy) demonstrated clinically meaningful antitumor activity.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2590018825000140

A phase 2 study of nivolumab, ipilimumab, and radiation in ... Combined ipilimumab, nivolumab, influenza vaccine, and SBRT therapy in patients with PC was feasible but did not lead to objective responses.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12140036/

A phase II study of nivolumab, ipilimumab, and radiation in ... The combination therapy did not show antitumor efficacy. •. No unexpected safety concerns were identified with the treatment. Introduction.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03104439

Study Details | NCT03104439 | Nivolumab and Ipilimumab ... The antibodies in ipilimumab work by not allowing cancer cell growth. The antibodies in nivolumab work by causing programmed cell death of the cancer cells.