Cancer Vaccine + Pembrolizumab for Advanced Cancers

(PNeoVCA Trial)

Overseen By Yanyan Lou, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Mayo Clinic

Must be taking: Pembrolizumab

Must not be taking: Systemic corticosteroids

Disqualifiers: Pregnancy, Autoimmune diseases, Heart failure, others

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

Compensation: Varies

Number of Visits: 4

Duration: Up to 2 years

36 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that certain therapies, like chemotherapy or experimental drugs, should not be taken within a few weeks before registration. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of this treatment for advanced cancers?

Research shows that combining personalized vaccines with drugs like pembrolizumab can boost the body's immune response against cancer cells. In studies, this approach has been well tolerated and has shown promise in enhancing the body's ability to fight tumors. ^{1 2 3 4 5}

Is the cancer vaccine with Pembrolizumab safe for humans?

The cancer vaccine, when tested in various forms and combinations, has generally been found to be safe in humans. Most side effects were mild, such as fatigue or skin reactions at the injection site, and serious side effects were rare and self-limiting. ^{4 6 7 8 9}

How is the cancer vaccine with pembrolizumab treatment different from other cancer treatments?

This treatment combines a cancer vaccine with pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells more effectively. Unlike traditional chemotherapy, pembrolizumab specifically targets the PD-1 pathway to enhance the body's immune response against tumors, potentially offering a more targeted and less toxic approach. ^{10 11 12 13 14}

What is the purpose of this trial?

This phase I trial tests the safety and tolerability of an experimental personalized vaccine when given by itself and with pembrolizumab in treating patients with solid tumor cancers that have spread to other places in the body (advanced). The experimental vaccine is designed target certain proteins (neoantigens) on individuals' tumor cells. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving the personalized neoantigen peptide-based vaccine with pembrolizumab may be safe and effective in treating patients with advanced solid tumors.

Research Team

Yanyan Lou, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

Adults with advanced solid tumors that have spread and are not treatable by surgery. Participants must have a life expectancy over 6 months, adequate organ function, and agree to use effective contraception. They should be willing to provide tissue samples for research and not have other active cancers or severe diseases.

Inclusion Criteria

My cancer has worsened after receiving standard treatment.

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

I have recovered from side effects of my previous cancer treatments.

Exclusion Criteria

REGISTRATION: Nursing persons

I had a severe reaction to previous immunotherapy that needed steroids or stopped treatment.

I haven't taken steroids or immunosuppressants in the last 14 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive cyclophosphamide, personalized neoantigen vaccine, and pembrolizumab in 21-day cycles

Up to 2 years

Multiple visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Every 3 months (in-person)

Treatment Details

Interventions

• Neoantigen Peptide Vaccine
• Pembrolizumab

Trial Overview The trial is testing the safety of a new personalized cancer vaccine combined with Pembrolizumab (an existing immunotherapy drug) in patients with various types of advanced solid tumors. The vaccine targets specific proteins on tumor cells to help the immune system fight cancer.

Participant Groups

Group I: Treatment (cyclophosphamide, vaccine, pembrolizumab) Experimental Treatment 4 Interventions

Patients receive cyclophosphamide IV on day -3. Patients then receive personalized neoantigen vaccine with sargramostim SC on days 1, 4, 8, and 15 of cycle 1 and day 1 of cycles thereafter. Patients also receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients may undergo blood sample collection during screening, cycle 1 days -3, 1, 8, 15, 22, cycles 2, 3, 4, 5, 7, 8 and 9+ day 1 and 30 days after last dose of GM-CSF or pembrolizumab and may undergo tissue biopsy during screening, week 25 or at the time of disease progression. Patients also undergo CT or MRI during screening, week 9 then every 9 weeks, and 30 days after last dose of GM-CSF or pembrolizumab.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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 phase 1b clinical trial showed that the combination of the personalized vaccine NEO-PV-01 with chemotherapy and the anti-PD-1 drug pembrolizumab was well tolerated in patients with first-line metastatic non-squamous NSCLC.

This treatment regimen successfully induced specific CD4+ T cell responses targeting neoantigens, suggesting a promising mechanism for enhancing the immune response against cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining personalized neoantigen vaccination with chemotherapy and anti-PD-1 to treat NSCLC. Leung, CSK., Van den Eynde, BJ.[2022]

A phase 1B study demonstrated that a personalized neoantigen vaccine combined with PD-1 blockade can stimulate strong T cell responses in patients with advanced cancers.

This combination therapy shows potential for enhancing tumor destruction and improving clinical outcomes, suggesting a promising approach for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can Personalized Neoantigens Raise the T Cell Bar? Zaidi, N.[2022]

The combination of personalized peptide vaccination (PPV) and estramustine phosphate (EMP) was found to be safe for patients with castration-resistant prostate cancer (CRPC), with no serious treatment-related adverse events reported and only mild skin reactions observed.

The treatment successfully boosted immune responses in a significant portion of patients, with 67% showing enhanced cytotoxic T lymphocyte responses, and a median survival time of 23.8 months, suggesting promising antitumor activity that warrants further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of personalized peptide vaccination using 14 kinds of vaccine in combination with low-dose estramustine in HLA-A24-positive patients with castration-resistant prostate cancer. Noguchi, M., Uemura, H., Naito, S., et al.[2013]

The combination of personalized peptide vaccination and low-dose glucocorticoids was well tolerated in 11 patients with advanced hormone refractory prostate cancer, showing no severe adverse effects.

The treatment led to significant immunological responses, with increased IgG responses in 8 out of 10 patients receiving dexamethasone, and a notable decline in PSA levels in 6 out of 10 patients, suggesting potential clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexamethasone did not suppress immune boosting by personalized peptide vaccination for advanced prostate cancer patients. Naito, M., Itoh, K., Komatsu, N., et al.[2013]

In a phase I/II study involving 16 HLA-A24+ hormone refractory prostate cancer patients, the combination of individualized peptide vaccination and a low dose of estramustine was well tolerated, with only mild local reactions at the injection site and no significant immunosuppression observed.

The treatment led to a decrease in serum prostate-specific antigen (PSA) levels in all patients receiving combination therapy, with six patients showing a reduction of over 50%, while quality of life outcomes remained stable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunological evaluation of individualized peptide vaccination with a low dose of estramustine for HLA-A24+ HRPC patients. Noguchi, M., Itoh, K., Yao, A., et al.[2020]

The KRM-20 cancer vaccine, which targets 12 different tumor-associated antigens, was found to be safe in a study of 17 patients with castration-resistant prostate cancer, with no serious adverse reactions reported.

The 20 mg dose of KRM-20 showed the best immune response, leading to increased cytotoxic T lymphocyte activity and fewer immune suppressive cells, making it a promising candidate for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of a cancer vaccine consisting of 20 mixed peptides in patients with castration-resistant prostate cancer: dose-related immune boosting and suppression. Noguchi, M., Arai, G., Matsumoto, K., et al.[2015]

In a pilot clinical trial involving 11 participants with advanced colorectal cancer, vaccination with CEA and Her2 peptides was found to be well tolerated, with 82% of adverse events being mild (Grade 1-2), primarily fatigue and injection site reactions.

The vaccination induced immune responses in 70% of participants and resulted in a median overall survival of 16 months, suggesting potential benefits that warrant further investigation, especially in combination with existing checkpoint-blockade therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot trial of vaccination with Carcinoembryonic antigen and Her2/neu peptides in advanced colorectal cancer. Lynch, KT., Squeo, GC., Kane, WJ., et al.[2021]

In a phase I study involving 10 patients with metastatic hormone-refractory prostate cancer, peptide vaccination was found to be safe and well tolerated, with no major adverse effects reported, although some patients experienced mild dermatologic reactions at the injection site.

The vaccination led to increased immune responses in some patients, with one patient showing a complete disappearance of a pelvic bone metastasis and three patients experiencing a decrease in serum PSA levels, suggesting potential efficacy and warranting further research into this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I trial of patient-oriented vaccination in HLA-A2-positive patients with metastatic hormone-refractory prostate cancer. Noguchi, M., Itoh, K., Suekane, S., et al.[2020]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

Pembrolizumab (Keytruda) effectively blocks the PD-1 pathway, enhancing T-cell activity against tumors, which supports its role in promoting tumor regression and immune rejection.

Preclinical studies in cynomolgus monkeys showed that pembrolizumab has a favorable safety profile with no significant toxicological findings, aligning with its demonstrated safety and efficacy in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. Hutchins, B., Starling, GC., McCoy, MA., et al.[2021]

References

1. 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]

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

Combining personalized neoantigen vaccination with chemotherapy and anti-PD-1 to treat NSCLC. [2022]

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

Can Personalized Neoantigens Raise the T Cell Bar? [2022]

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

A phase I study of personalized peptide vaccination using 14 kinds of vaccine in combination with low-dose estramustine in HLA-A24-positive patients with castration-resistant prostate cancer. [2013]

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

Dexamethasone did not suppress immune boosting by personalized peptide vaccination for advanced prostate cancer patients. [2013]

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

Immunological evaluation of individualized peptide vaccination with a low dose of estramustine for HLA-A24+ HRPC patients. [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

Phase I trial of a cancer vaccine consisting of 20 mixed peptides in patients with castration-resistant prostate cancer: dose-related immune boosting and suppression. [2015]

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

A pilot trial of vaccination with Carcinoembryonic antigen and Her2/neu peptides in advanced colorectal cancer. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Phase I trial of patient-oriented vaccination in HLA-A2-positive patients with metastatic hormone-refractory prostate cancer. [2020]

10. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

Biophysical and Immunological Characterization and In Vivo Pharmacokinetics and Toxicology in Nonhuman Primates of the Anti-PD-1 Antibody Pembrolizumab. [2021]