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

Trial Summary

What is the purpose of this trial?

This trial tests a custom-made vaccine for patients with advanced melanoma or breast cancer that has spread or is resistant to treatment. The vaccine helps the immune system recognize and attack cancer cells using specific markers from the patient's tumor, boosted by additional substances. Melanoma has been a model disease for testing novel vaccine designs due to its intrinsic immunogenicity.

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.

What data supports the effectiveness of the treatment Neoantigen Peptide Vaccine, Nivolumab, Opdivo, Poly ICLC, Poly ICLC, Polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose for melanoma?

Research shows that combining vaccines with drugs like Nivolumab can help the immune system fight melanoma more effectively. In some studies, patients with melanoma have shown positive responses to similar treatments, although the success rate is less than 20%. ^{1 2 3 4 5}

Is the cancer vaccine for melanoma, including treatments like Nivolumab, generally safe for humans?

Nivolumab, also known as Opdivo, has been studied in several clinical trials and is generally considered safe for humans, with common side effects including fatigue, rash, itching, diarrhea, and nausea. Serious side effects are less common, but can include low phosphate levels and low white blood cell counts. The rate of death related to Nivolumab is very low, at 0.25%. ^{6 7 8 9 10}

How is the cancer vaccine for melanoma treatment different from other treatments?

This treatment combines a neoantigen peptide vaccine with nivolumab (Opdivo), which is unique because it targets specific proteins on cancer cells and immune cells to enhance the body's immune response against melanoma, potentially improving outcomes compared to using nivolumab alone. ^{1 11 12 13 14}

Research Team

Joshua Veatch

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

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 am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

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 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 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]

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]

References

1. England 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. [2023]

2. United States 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). [2021]

3. Switzerland 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. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Peptide-based cancer vaccines. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Novel immunologic approaches to the management of malignant melanoma. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval of Nivolumab for the First-Line Treatment of Patients with BRAFV600 Wild-Type Unresectable or Metastatic Melanoma. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nivolumab in the treatment of cancers: A meta-analysis of 27 prospective clinical trials. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

U.S. FDA Approval Summary: Nivolumab for Treatment of Unresectable or Metastatic Melanoma Following Progression on Ipilimumab. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. [2022]

10. United States 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. [2021]

11. United States 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. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Vaccination with Melanoma Helper Peptides Induces Antibody Responses Associated with Improved Overall Survival. [2021]

13. United States 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. [2023]

14. Germany pubmed.ncbi.nlm.nih.gov

Long-term outcomes in patients with metastatic melanoma vaccinated with melanoma peptide-pulsed CD34(+) progenitor-derived dendritic cells. [2020]