Cancer Vaccine + Nivolumab + Ipilimumab for Pancreatic and Colorectal Cancer

Overseen By Colleen Apostol, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Steroids, Chemotherapy, Immunotherapy, others

Disqualifiers: Autoimmune disease, Brain metastases, HIV, others

Stay on Your Current Meds You can continue your current medications while participating

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and immune response of a new cancer vaccine combined with two drugs, nivolumab (Opdivo) and ipilimumab (Yervoy), for patients with pancreatic cancer or metastatic colorectal cancer. It focuses on those who recently underwent chemotherapy or radiation for pancreatic cancer or those with colorectal cancer who have completed several rounds of chemotherapy. Good candidates include those diagnosed with these cancers and possessing specific genetic mutations in their tumors. Participants will help researchers understand the treatment's effectiveness and potential side effects. As a Phase 1 trial, the research focuses on understanding the treatment's effects in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting, such as systemic steroids, chemotherapy, and investigational drugs. If you're on these, you may need to stop them 2 to 4 weeks before the trial begins.

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

Research has shown that the KRAS peptide vaccine, combined with the drugs nivolumab and ipilimumab, has been tested in people. These studies aim to determine the safety and effectiveness of this treatment. Some patients have received this combination to observe their body's response. Early results suggest that most participants tolerated the treatment well.

As with any treatment, reports of side effects have occurred. Common side effects for this combination include fatigue, skin rash, and mild digestive issues. These effects are typical and expected with such treatments. The studies remain in the early stages, focusing primarily on ensuring safety and understanding the treatment's mechanism in the body. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of the KRAS peptide vaccine with Nivolumab and Ipilimumab because this treatment directly targets mutations in the KRAS gene, which are common in pancreatic and colorectal cancers. Unlike standard chemotherapy or targeted therapies, this approach aims to train the immune system to recognize and attack cancer cells specifically. Nivolumab and Ipilimumab are immune checkpoint inhibitors that help amplify the immune response, potentially leading to a more effective and sustained attack on the cancer. This innovative combination could provide a powerful new option for patients with these difficult-to-treat cancers.

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

Research has shown that combining the KRAS peptide vaccine with the drugs nivolumab and ipilimumab may help treat pancreatic and colorectal cancers. In this trial, participants will receive this combination, which has improved survival rates for some patients with these cancers. The KRAS peptide vaccine targets specific changes in cancer cells, potentially enhancing the immune system's ability to fight the cancer. Nivolumab and ipilimumab boost the immune system's capacity to find and attack cancer cells. Early results suggest that this combination can lead to better outcomes for patients with certain changes in their cancer. These findings support the potential effectiveness of this treatment combination in managing these cancers. ^{1 3 4 6 7}

Who Is on the Research Team?

Nilofer Azad, MD

Principal Investigator

Johns Hopkins Medical Institution

Are You a Good Fit for This Trial?

Adults over 18 with certain types of pancreatic or colorectal cancer that's been surgically removed and who've had previous chemotherapy can join. They must be in good health, have a life expectancy over 6 months, and use birth control. People can't join if they're on high-dose steroids, had recent radiation or chemo, prior immunotherapy, severe allergies to antibodies, active autoimmune diseases, serious infections including HIV/hepatitis B/C, brain metastases or need oxygen therapy.

Inclusion Criteria

I am a man and will use birth control during the study.

I am fully active or restricted in physically strenuous activity but can do light work.

My cancer has returned in one specific area, as shown on scans.

Exclusion Criteria

I haven't had any radiation treatment or gamma knife surgery in the last 2 weeks.

Within 4 weeks prior to first dose of study drug: Any investigational device

I haven't taken high-dose steroids in the last 2 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the KRAS Vaccine Peptide, Nivolumab, and Ipilimumab

16 weeks

Regular visits for treatment administration and monitoring

Reinduction Treatment

Participants may receive additional doses of KRAS Vaccine Peptide, Nivolumab, and Ipilimumab

Variable, based on response

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Periodic visits for assessment

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• KRAS peptide vaccine
• Nivolumab

Trial Overview This Phase 1 trial tests the safety and immune response to a new KRAS peptide vaccine combined with Nivolumab and Ipilimumab in patients with specific types of pancreatic and colorectal cancers. The study will see how well this combination works after surgery and standard treatments.

How Is the Trial Designed?

Group I: Treatment Phase Experimental Treatment 3 Interventions

KRAS Vaccine Peptide, Nivolumab and Ipilimumab

Group II: Reinduction Treatment Phase Experimental Treatment 3 Interventions

KRAS Vaccine Peptide, Nivolumab and Ipilimumab

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?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

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

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

The novel PD-1 B-cell peptide vaccine (PD1-Vaxx) demonstrated superior efficacy compared to standard anti-PD-1 monoclonal antibodies in preclinical mouse models of colon carcinoma, suggesting it may be a promising alternative for cancer treatment.

Combining PD1-Vaxx with a HER-2 peptide vaccine resulted in enhanced tumor growth inhibition, and both vaccines showed a favorable safety profile with no observed toxicity or autoimmunity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and antitumor efficacy of a novel human PD-1 B-cell vaccine (PD1-Vaxx) and combination immunotherapy with dual trastuzumab/pertuzumab-like HER-2 B-cell epitope vaccines (B-Vaxx) in a syngeneic mouse model. Kaumaya, PTP., Guo, L., Overholser, J., et al.[2021]

The multipeptide vaccine targeting KRAS mutations demonstrated over 80% reduction in tumor number and burden in a mouse model, indicating strong antitumor efficacy before the mutant KRAS protein was activated.

The vaccine elicited a robust immune response characterized by Th1 cytokine secretion, suggesting it could be an effective preventive strategy against KRAS-driven lung cancer and potentially other cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunoprevention of KRAS-driven lung adenocarcinoma by a multipeptide vaccine. Pan, J., Zhang, Q., Sei, S., et al.[2019]

The WT1/MUC1 dendritic cell vaccination was found to be safe and well-tolerated in 10 patients with surgically resectable pancreatic ductal adenocarcinoma, with no significant toxicities reported.

Preliminary results showed promising overall survival rates at 3 years (77.8%) and a potential link between the vaccination and increased immune response in tumor tissues, suggesting further investigation is needed to assess its clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dendritic Cell-based Immunotherapy Pulsed With Wilms Tumor 1 Peptide and Mucin 1 as an Adjuvant Therapy for Pancreatic Ductal Adenocarcinoma After Curative Resection: A Phase I/IIa Clinical Trial. Nagai, K., Adachi, T., Harada, H., et al.[2022]

The combination of GVAX vaccine with nivolumab and urelumab significantly increased the number of activated CD8+ CD137+ T cells in tumors, indicating a robust immune response, and was well-tolerated by patients.

While the median disease-free and overall survival rates were numerically improved with the combination therapy compared to other treatment arms, the results were not statistically significant, suggesting that further studies are needed to confirm these promising findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A platform trial of neoadjuvant and adjuvant antitumor vaccination alone or in combination with PD-1 antagonist and CD137 agonist antibodies in patients with resectable pancreatic adenocarcinoma. Heumann, T., Judkins, C., Li, K., et al.[2023]

Del19 mutations of the EGFR gene are prevalent in about 40% of Chinese lung adenocarcinoma patients and can be effectively targeted for immunotherapy, as they are presented by multiple HLA Class I and II molecules.

Patients with Del19 EGFR mutations show significantly higher immune responses to the wild type EGFR protein compared to those with other mutations, indicating the potential for developing effective cancer vaccines based on these mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity of Del19 EGFR mutations in Chinese patients affected by lung adenocarcinoma. Pan, D., Zhou, D., Cai, W., et al.[2020]

In a phase I/II trial involving 48 patients with pancreatic adenocarcinoma, a vaccine using synthetic mutant ras peptides successfully induced an immune response in 58% of evaluable patients, demonstrating its potential effectiveness even in advanced disease stages.

Patients who developed an immune response to the vaccine had a significantly longer median survival (148 days) compared to non-responders (61 days), suggesting that the vaccine may provide clinical benefits for patients with pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intradermal ras peptide vaccination with granulocyte-macrophage colony-stimulating factor as adjuvant: Clinical and immunological responses in patients with pancreatic adenocarcinoma. Gjertsen, MK., Buanes, T., Rosseland, AR., et al.[2021]

Cancer vaccine therapy shows promise for treating pancreatic cancer due to its ability to stimulate a cancer-specific immune response with fewer side effects, which is important for patients often diagnosed in poor health.

While recent clinical trials combining cancer vaccines with traditional therapies have not consistently outperformed standard treatments, there is potential for improvement by integrating immune-checkpoint inhibitors and multi-drug chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination treatment of advanced pancreatic cancer using novel vaccine and traditional therapies. Matsui, H., Hazama, S., Shindo, Y., et al.[2019]

The study proposes that combining personalized cancer vaccines with PD-1 blockade therapy can enhance the immune response in pancreatic cancer patients, particularly those with non-inflamed tumors that typically resist treatment.

Using a vaccine platform with autologous dendritic cells loaded with personalized neoantigen peptides, along with the PD-1 antibody nivolumab, aims to improve tumor recognition and response to therapy, demonstrating feasibility in three pancreatic cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of the Combination of Personalized Autologous Dendritic Cell Vaccine, Aspirin, and Standard of Care Adjuvant Chemotherapy Followed by Nivolumab for Resected Pancreatic Adenocarcinoma-A Proof of Antigen Discovery Feasibility in Three Patients. Bassani-Sternberg, M., Digklia, A., Huber, F., et al.[2023]

In a study involving 93 patients with metastatic pancreatic cancer, combining GVAX vaccine and cyclophosphamide with nivolumab (Arm A) did not significantly improve overall survival compared to the same treatment without nivolumab (Arm B), with median survival times of 5.9 and 6.1 months, respectively.

Despite not meeting the primary endpoint, Arm A showed some objective tumor responses and beneficial immunologic changes in long-term survivors, such as increased CD8+ T cells, suggesting potential for immune modulation even if overall survival was similar to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Cyclophosphamide/GVAX Pancreas Followed by Listeria-Mesothelin (CRS-207) with or without Nivolumab in Patients with Pancreatic Cancer. Tsujikawa, T., Crocenzi, T., Durham, JN., et al.[2023]

The multi-target vaccine composed of peptides from cancer-testis antigens and VEGFRs was well-tolerated in a Phase I trial with 9 patients suffering from advanced pancreatic cancer, showing no severe adverse events.

Four out of nine patients experienced clinical benefits, with median progression-free survival of 90 days and overall survival of 207 days, indicating potential efficacy of the vaccine in this difficult-to-treat population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunological responses to a multi-peptide vaccine targeting cancer-testis antigens and VEGFRs in advanced pancreatic cancer patients. Okuyama, R., Aruga, A., Hatori, T., et al.[2021]

The phase II clinical trial involving 12 patients demonstrated that a mutant ras peptide vaccine is safe, with no serious side effects reported, and can induce specific immune responses in some patients.

Patients with pancreatic cancer showed a mean overall survival of 44.4 months and disease-free survival of 35.2 months, while colorectal cancer patients had a mean overall survival of 41.5 months and disease-free survival of 27.2 months, suggesting the vaccine may positively impact survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of mutant ras peptide-based vaccine as an adjuvant treatment in pancreatic and colorectal cancers. Toubaji, A., Achtar, M., Provenzano, M., et al.[2020]

Citations

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Pooled Mutant KRAS-Targeted Long Peptide Vaccine ... A phase I study of a mutant KRAS-targeted long peptide vaccine combined with ipilimumab/nivolumab in resected pancreatic cancer and MMR-proficient metastatic ...

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KRAS Peptide Vaccine, Nivolumab, and Ipilimumab for the ... This phase I trial is to find out the possible benefits and/or side effects of KRAS peptide vaccine, nivolumab, and ipilimumab in treating patients with ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4919239/

Current progress in immunotherapy for pancreatic cancer More recently as shown in a phase III study, median progression-free survival was 11.5 months following treatment with ipilimumab in combination with nivolumab ...

5. mskcc.org mskcc.org/news/vaccine-targeting-kras-in-pancreatic-and-colorectal-cancer-shows-promise

Vaccine Targeting KRAS in Pancreatic and Colorectal ... The phase 1 trial involved 25 patients whose pancreatic or colorectal cancer had certain KRAS mutations and were at high risk of the cancer ...

6. aacrjournals.org aacrjournals.org/cancerres/article/83/8_Supplement/CT036/725326/Abstract-CT036-Safety-and-immunogenicity-of-a

Abstract CT036: Safety and immunogenicity of a first-in-human ... Safety and immunogenicity of a first-in-human mutant KRAS long peptide vaccine combined with ipilimumab/nivolumab in resected pancreatic cancer: ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11430323/

Fighting Pancreatic Cancer with a Vaccine-Based Winning ... The median overall survival time was 5.88 months in arm 1 and 6.11 months in arm 2, while the median progression-free survival was 2.23 months (arm 1) and 2.17 ...