Peptide Vaccine for ALK+ Lung Cancer

Overseen By Peggy Fitzpatrick, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must be taking: ALK targeted therapy

Must not be taking: Cytotoxic chemotherapy, Immunotherapy, Steroids

Disqualifiers: Additional malignancy, CNS metastasis, Spinal cord compression, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

12 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety of a cancer peptide vaccine to prevent or delay acquired resistance in advanced ALK+ lung cancer patients currently on ALK targeted therapy.

Do I need to stop my current medications for the trial?

You can continue taking your current ALK targeted therapy medications like crizotinib, ceritinib, alectinib, brigatinib, or lorlatinib while participating in the trial.

What data supports the effectiveness of the treatment for ALK+ lung cancer?

Research shows that a peptide vaccine can help the immune system recognize and attack ALK+ lung cancer cells, especially when combined with other treatments. In studies, this approach helped reduce lung tumors and prevent them from spreading to the brain. ^{1 2 3 4 5}

Is the peptide vaccine for ALK+ lung cancer safe for humans?

A review of clinical trials for non-small cell lung cancer vaccines, including peptide-based ones, shows they consistently demonstrate a lack of toxicity, indicating they are generally safe for humans. ^{1 2 3 6 7}

How is the Prophylactic Peptide Vaccine treatment different from other treatments for ALK+ lung cancer?

The Prophylactic Peptide Vaccine is unique because it specifically targets ALK+ lung cancer by stimulating the immune system to recognize and attack cancer cells, which is different from traditional treatments like ALK inhibitors that directly target cancer cell growth. This vaccine approach helps the immune system to better identify and destroy cancer cells, potentially preventing the spread of tumors. ^{1 2 3 8 9}

Research Team

Vincent Lam, M.D.

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults over 18 with advanced ALK+ lung cancer who are responding to current ALK targeted therapy and have a good performance status. They must not have specific resistance alterations the vaccine targets, and their diagnosis should be confirmed by certain tests.

Inclusion Criteria

My lung cancer is at stage IV or has come back and cannot be treated with surgery or radiation.

I've been on ALK inhibitors for 4+ months with stable disease.

I am fully active or can carry out light work.

Exclusion Criteria

I haven't had active treatment for another cancer within the last 3 years, except for certain skin cancers or cancers treated with the intent to cure.

I haven't had chemotherapy in the last 14 days or while on the study vaccine.

I haven't had cancer immunotherapy in the last 28 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the cancer peptide vaccine to prevent or delay acquired resistance in advanced ALK+ lung cancer

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Prophylactic Peptide Vaccine

Trial Overview The study is testing a peptide vaccine's safety in preventing or delaying drug resistance in patients with advanced ALK+ lung cancer who are already on an ALK inhibitor treatment.

Participant Groups

Group I: Advanced ALK+ NSCLC Experimental Treatment 1 Intervention

All patients will receive the intervention

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Findings from Research

ALK-rearranged non-small cell lung cancer (NSCLC) shows poor response to immune checkpoint inhibitors (ICIs) due to ineffective priming of CD8+ T cells against ALK antigens, but this can be improved with specific vaccination.

A single-peptide vaccination not only restored the priming of ALK-specific CD8+ T cells but also eradicated lung tumors when combined with ALK tyrosine kinase inhibitors (TKIs) and prevented metastasis to the brain, suggesting a promising new treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ALK peptide vaccination restores the immunogenicity of ALK-rearranged non-small cell lung cancer. Mota, I., Patrucco, E., Mastini, C., et al.[2023]

Vaccines designed to enhance tumor antigen recognition in non-small cell lung cancer patients show promising results, including prolonged stable disease and tumor shrinkage, with no reported toxicity.

Specific vaccines such as LBLP25, TGF-beta2 antisense gene vaccine, and GVAX have demonstrated potential benefits that warrant further Phase III clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of vaccine clinical trials for non-small cell lung cancer. Nemunaitis, J., Nemunaitis, J.[2019]

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]

Active immunotherapy using peptide vaccines to stimulate tumor-specific T cells has become a recognized treatment option for cancer, showing promise in various clinical trials over the past three years.

The review emphasizes the need for developing peptide vaccines specifically for non-small-cell lung cancer, which is the leading cause of cancer-related deaths, highlighting the potential for improved clinical outcomes through targeted T-cell responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent progress in peptide vaccination in cancer with a focus on non-small-cell lung cancer. Talebian Yazdi, M., Keene, KR., Hiemstra, PS., et al.[2014]

Peptide cancer vaccines aim to stimulate the immune system against tumor-associated and tumor-specific antigens, but their effectiveness depends on selecting the right antigens, adjuvants, and immunization methods.

Personalized peptide-based vaccines targeting neoantigens and combining them with chemotherapy or immune checkpoint inhibitors are being explored to enhance antitumor responses and improve overall treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Peptide-Based Vaccines for Cancer. Abd-Aziz, N., Poh, CL.[2022]

A 71-year-old woman with metastatic renal cell carcinoma showed remarkable tumor shrinkage after receiving nivolumab, an immune checkpoint inhibitor, following unsuccessful treatment with a cancer-specific peptide vaccine.

Even after stopping nivolumab due to side effects, the patient maintained a complete response for over a year, suggesting a lasting antitumor effect from the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Remarkable antitumor effect of nivolumab in a patient with metastatic renal cell carcinoma previously treated with a peptide-based vaccine. Kurahashi, R., Motoshima, T., Fukushima, Y., et al.[2022]

In a study of 127 lung cancer patients receiving nivolumab, influenza vaccination did not significantly increase the incidence of immune-related adverse events (irAEs) compared to non-vaccinated patients, with rates of 26% for vaccinated and 22% for non-vaccinated individuals.

The study found no significant differences in serious irAEs, treatment discontinuation, death, or tumor response between vaccinated and non-vaccinated groups, suggesting that influenza vaccination is safe and should be encouraged for lung cancer patients undergoing anti-PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza vaccination in patients with lung cancer receiving anti-programmed death receptor 1 immunotherapy does not induce immune-related adverse events. Wijn, DH., Groeneveld, GH., Vollaard, AM., et al.[2019]

Peptide-based anticancer vaccines have shown limited effectiveness in clinical settings due to cancer cells' ability to reduce antigen visibility and the immunosuppressive nature of the tumor environment.

To enhance their therapeutic potential, strategies such as using immunostimulatory adjuvants, combining with cytotoxic therapies, and blocking immune checkpoints are being explored, along with personalized peptide vaccines tailored to individual patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial watch: Peptide-based vaccines in anticancer therapy. Bezu, L., Kepp, O., Cerrato, G., et al.[2021]

Peptide vaccines targeting tumor-associated antigens (TAAs) have shown promising antineoplastic effects in various mouse models, especially when combined with strong immunostimulatory regimens.

Current research is focused on identifying tumor rejection antigens that can effectively trigger immune responses to eradicate cancer, along with developing better adjuvants to enhance the efficacy of these vaccines in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trial Watch: Peptide-based anticancer vaccines. Pol, J., Bloy, N., Buqué, A., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

ALK peptide vaccination restores the immunogenicity of ALK-rearranged non-small cell lung cancer. [2023]

2. England pubmed.ncbi.nlm.nih.gov

A review of vaccine clinical trials for non-small cell lung cancer. [2019]

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

Immunoprevention of KRAS-driven lung adenocarcinoma by a multipeptide vaccine. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Recent progress in peptide vaccination in cancer with a focus on non-small-cell lung cancer. [2014]

5. Egypt pubmed.ncbi.nlm.nih.gov

Development of Peptide-Based Vaccines for Cancer. [2022]

6. Australia pubmed.ncbi.nlm.nih.gov

Remarkable antitumor effect of nivolumab in a patient with metastatic renal cell carcinoma previously treated with a peptide-based vaccine. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Influenza vaccination in patients with lung cancer receiving anti-programmed death receptor 1 immunotherapy does not induce immune-related adverse events. [2019]

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

Trial watch: Peptide-based vaccines in anticancer therapy. [2021]

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

Trial Watch: Peptide-based anticancer vaccines. [2021]