Cancer Vaccine for Melanoma

Overseen By FHCC Intake

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Fred Hutchinson Cancer Research Center

Must not be taking: Systemic immunosuppressants

Disqualifiers: Uncontrolled infection, Autoimmune disease, 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)

Compensation: Varies

Number of Visits: 4

Duration: 25 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a personalized cancer vaccine for individuals with advanced melanoma, certain types of metastatic breast cancer, or non-small cell lung cancer. The goal is to determine if this vaccine, when combined with other treatments, safely and effectively activates the body's immune response against cancer. Participants should have one of these cancers that has spread or is not responding to standard treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works 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 protocol does not specify if you need to stop taking your current medications. However, it mentions that treatment with certain systemic immunosuppressive medications should be stopped at least 2 weeks before screening. It's best to discuss your specific medications with the study team.

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

Previous studies have shown that personalized neoantigen peptide vaccines are safe and well-tolerated. These vaccines target specific proteins in a person's cancer, and research indicates they can effectively trigger an immune response without causing severe side effects.

Nivolumab, another part of this treatment, already treats melanoma and other cancers. About 42% of patients report severe reactions, but doctors manage these known side effects.

Poly ICLC, used to boost the immune system, has also undergone testing in other trials. It is generally considered safe, though it can have side effects like any treatment.

Overall, this combination has been researched for safety, but discussing any concerns with a doctor is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this cancer vaccine for melanoma because it offers a personalized approach. Unlike standard treatments like surgery, chemotherapy, and radiation, this vaccine targets specific neoantigens unique to each patient's tumor. This means the immune system can more precisely attack cancer cells without harming healthy cells. Additionally, combining the vaccine with nivolumab, an immune checkpoint inhibitor, could enhance the immune response, potentially leading to better outcomes than current therapies. This innovative approach could pave the way for more effective, targeted cancer treatments.

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

Research has shown that personalized vaccines, known as neoantigen peptide vaccines, can activate strong T cell responses, which are crucial for attacking cancer cells. These vaccines target specific markers on a patient's tumor, potentially increasing their effectiveness. For melanoma, early studies demonstrated that these vaccines can be safe and practical. In this trial, participants will receive a combination of treatments, including the neoantigen peptide vaccine, Nivolumab, and poly ICLC. Nivolumab has improved survival rates in melanoma patients by helping the immune system better recognize and fight cancer cells. Poly ICLC enhances immune responses, potentially making the combination more effective against tumors. ^{3 6 7 8 9}

Who Is on the Research Team?

Joshua Veatch

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

Adults over 18 with advanced melanoma or hormone receptor positive, HER2 negative breast cancer that's spread or is treatment-resistant. They must be in good enough health to participate, have measurable disease, and agree to follow the study plan. People with heart issues, severe liver problems, certain blood conditions or active infections can't join. Women of childbearing age must use contraception.

Inclusion Criteria

Your hemoglobin level is 9 mg/dL or higher.

We don't know how a neoantigen vaccination might affect a growing baby inside a pregnant woman.

I have recovered from previous cancer treatment side effects to a mild level.

Exclusion Criteria

I am currently breastfeeding or plan to during the study.

I haven't taken any immune-weakening drugs in the last 2 weeks.

I currently have a fever due to an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive poly ICLC intramuscularly once weekly, personalized neo-antigen peptide vaccine every 4 weeks, and nivolumab every 2 or 4 weeks for 25 weeks

25 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion at 24, 36, and 48 weeks

48 weeks

3 visits (in-person)

Extension

Patients may continue nivolumab every 2 or 4 weeks for up to 12 months if they benefit from the initial treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Neoantigen Peptide Vaccine
• Nivolumab
• Poly ICLC

Trial Overview The trial tests a personalized neo-antigen peptide vaccine combined with an adjuvant called poly ICLC on patients with specific types of melanoma and breast cancer. The goal is to see if this vaccine can trigger the body's T cells to fight the patient’s tumor more effectively.

How Is the Trial Designed?

Group I: Treatment (poly ICLC, neo-antigen peptide vaccine, nivolumab) Experimental Treatment 9 Interventions

Patients receive poly ICLC IM once weekly in weeks when no vaccine is given. Beginning 2 weeks after starting poly ICLC, patients receive personalized neo-antigen peptide vaccine IM once every 4 weeks and nivolumab IV every 2 or 4 weeks. Treatment continues for 25 weeks in the absence of disease progression or unacceptable toxicity. Patients determined to have clinical benefit on a first course of treatment may repeat a 6-month course of treatment as described above. Patients then receive nivolumab IV every 2 or 4 weeks for up to 12 months in the absence of disease progression or unacceptable toxicity. Additionally, patients may undergo ECHO or MUGA during screening. Patients also undergo tumor biopsy, blood sample collection, and CT and/or PET throughout the study.

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Recruited

148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Amazon.com Services LLC

Collaborator

Trials

2

Recruited

2,000+

Amazon, Inc.

Industry Sponsor

Trials

4

Recruited

2,400+

Published Research Related to This Trial

Nivolumab, administered at 3 mg/kg with or without a peptide vaccine, was well tolerated and demonstrated a 25% response rate in patients with advanced melanoma, regardless of prior ipilimumab treatment.

The study suggests that nivolumab can induce long-lasting responses, with some patients responding for up to 140 weeks, and highlights the potential for combining or sequencing nivolumab with ipilimumab for better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. Weber, JS., Kudchadkar, RR., Yu, B., et al.[2022]

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 cohort A, which included 30 patients with metastatic melanoma, the combination of an IDO/PD-L1 vaccine and nivolumab resulted in an impressive overall response rate of 80%, with 50% achieving a complete response and a median progression-free survival of 25.5 months.

Cohort B, where the vaccine was added to patients already on anti-PD-1 therapy, showed limited efficacy with only stable disease in 2 out of 10 patients and a median progression-free survival of just 2.4 months, indicating that the combination may not be effective for those with progressive disease during anti-PD-1 treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of anti-PD-1 naïve patients with metastatic melanoma treated with IDO/PD-L1 targeting peptide vaccine and nivolumab. Lorentzen, CL., Kjeldsen, JW., Ehrnrooth, E., et al.[2023]

In a phase 1/2 study involving 30 patients with metastatic melanoma, the combination of the immune-modulatory vaccine (IO102/IO103) with nivolumab showed a high objective response rate of 80%, with 43% of patients achieving complete responses.

The safety profile of the combination therapy was comparable to nivolumab alone, and after a median follow-up of nearly 23 months, the median progression-free survival was 26 months, indicating promising efficacy and tolerability for further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1/2 trial of an immune-modulatory vaccine against IDO/PD-L1 in combination with nivolumab in metastatic melanoma. Kjeldsen, JW., Lorentzen, CL., Martinenaite, E., et al.[2023]

Nivolumab significantly improved overall survival and progression-free survival in patients with unresectable or metastatic melanoma compared to dacarbazine, with hazard ratios of 0.42 and 0.43 respectively, based on a trial involving 418 patients.

The most common side effects of nivolumab included fatigue, diarrhea, and rash, but it was still considered to have a favorable benefit-risk profile compared to dacarbazine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma. Beaver, JA., Theoret, MR., Mushti, S., et al.[2018]

Nivolumab, an immune checkpoint inhibitor, shows a low rate of severe adverse effects (grade ≥3 AEs at 12%) and a very low mortality rate (0.25%), indicating it is a relatively safe treatment option for cancer patients.

In terms of efficacy, nivolumab demonstrates better treatment responses and survival rates compared to traditional chemotherapy, with a 1-year overall survival rate of 52% and a significantly higher objective response rate (ORR) of 26%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. Tie, Y., Ma, X., Zhu, C., et al.[2022]

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]

In a study involving 175 patients with advanced melanoma, the addition of melanoma helper peptides did not enhance cytotoxic T lymphocyte (CTL) responses to a melanoma vaccine, indicating that while the vaccines were immunogenic, they did not improve CTL activation.

However, a significant association was found between immune responses to the helper peptides and overall survival, suggesting that further research into helper peptide vaccines could be beneficial for improving treatment outcomes in advanced melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II trial of multiepitope vaccination with melanoma peptides for cytotoxic T cells and helper T cells for patients with metastatic melanoma (E1602). Slingluff, CL., Lee, S., Zhao, F., et al.[2021]

Peptide vaccines targeting tumor antigens have shown no major toxicity in cancer patients, particularly in melanoma, indicating a safe approach to immunotherapy.

However, the clinical efficacy of these vaccines is limited, with response rates below 20%, although some patients have experienced complete and long-lasting regressions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide-based cancer vaccines. Machiels, JP., van Baren, N., Marchand, M.[2019]

Recent advancements in identifying tumor antigens recognized by T cells have led to promising early-phase clinical trials of peptide vaccines for melanoma, showing immune and clinical responses in patients with both metastatic and resected disease.

The main challenge moving forward is to effectively link immunologic assay results with actual clinical benefits for patients suffering from advanced cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel immunologic approaches to the management of malignant melanoma. Weber, JS., Aparicio, A.[2019]

In a study of 35 patients with advanced melanoma, a vaccine using six helper peptides successfully induced antibody responses in 77% of patients by week 7, which persisted for at least 6 months.

Patients who developed both antibody and T-cell responses after vaccination had significantly improved survival rates, suggesting that these immune responses could be important indicators of clinical outcomes and may guide future immunotherapy strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccination with Melanoma Helper Peptides Induces Antibody Responses Associated with Improved Overall Survival. Reed, CM., Cresce, ND., Mauldin, IS., et al.[2021]

In a phase I trial involving 18 patients with metastatic melanoma, a dendritic cell vaccine showed promise, with a median overall survival of 20 months and median event-free survival of 7 months, indicating potential efficacy in this patient population.

Patients who developed immunity to at least two melanoma peptides had longer survival, suggesting that the vaccine's ability to elicit a strong immune response may be linked to better clinical outcomes, warranting further studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes in patients with metastatic melanoma vaccinated with melanoma peptide-pulsed CD34(+) progenitor-derived dendritic cells. Fay, JW., Palucka, AK., Paczesny, S., et al.[2020]

Nivolumab (OPDIVO) received accelerated FDA approval for treating unresectable or metastatic melanoma based on a 31.7% objective response rate in a study of 120 patients, showing promising efficacy after prior treatments.

The treatment demonstrated durable responses, with 87% of responding patients maintaining their response for at least 6 months, although it carries risks of immune-mediated adverse reactions that were monitored in a safety assessment of 268 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. FDA Approval Summary: Nivolumab for Treatment of Unresectable or Metastatic Melanoma Following Progression on Ipilimumab. Hazarika, M., Chuk, MK., Theoret, MR., et al.[2023]

In a meta-analysis of 11,465 patients from 18 clinical trials, PD-1/PD-L1 inhibitors were found to significantly increase the risk of developing dermatologic adverse effects like rash and pruritus compared to chemotherapy, with relative risks of 1.84 and 3.74, respectively.

PD-1/PD-L1 inhibitors showed a lower risk of mucosal inflammation and alopecia compared to chemotherapy, indicating a distinct safety profile that differs from traditional cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of dermatologic and mucosal adverse events associated with PD-1/PD-L1 inhibitors in cancer patients: A meta-analysis of randomized controlled trials. Yang, W., Li, S., Yang, Q.[2021]

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