Peptide Vaccine for ALK+ Lung Cancer

(ARCHER Trial)

Overseen By Shakila Rajack

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new peptide vaccine for individuals with advanced ALK+ lung cancer. It aims to determine if the vaccine can prevent or delay resistance to current treatments. The trial targets those with stage IV lung cancer who have a specific ALK gene change and have been on certain targeted therapies for at least four months with stable results. Participants should not have other active cancers or be on certain immune-suppressing 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 vaccine.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that the new vaccine for ALK+ lung cancer is undergoing tests to determine its safety for people. In earlier studies, patients who received this vaccine demonstrated a good immune response, helping their bodies better recognize and fight cancer cells.

So far, studies have not identified any serious side effects, suggesting the vaccine is generally safe. However, since this trial is in the early stages, the primary goal is to ensure the treatment's safety for everyone.

For those considering joining the trial, this is encouraging because the vaccine has shown a good safety record in earlier studies. It's important to discuss any questions with a doctor or the trial team to understand what this means for individual circumstances. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for ALK-positive lung cancer, like targeted therapies and chemotherapy, work by inhibiting specific proteins involved in cancer cell growth. But the peptide vaccine being studied works differently, aiming to stimulate the immune system to recognize and attack cancer cells specifically. This vaccine approach is unique because it potentially offers a more targeted immune response with fewer side effects compared to traditional chemotherapy. Researchers are particularly excited about its ability to provide long-term protection by training the immune system to remember and attack cancer cells if they reappear.

What evidence suggests that this peptide vaccine might be an effective treatment for ALK+ lung cancer?

Studies have shown that a vaccine targeting ALK can enhance the immune system's response in people with ALK-positive lung cancer. In studies with mice, this vaccine, especially when combined with other immune-boosting treatments, significantly improved survival rates. Clinical research suggests that patients who received the vaccine lived an average of 14.6 months, with survival times ranging from 10.6 to 18.8 months. Research indicates that the vaccine might slow the development of resistance to current ALK-targeted treatments, offering hope for better management of advanced lung cancer. In this trial, all participants will receive the Prophylactic Peptide Vaccine to evaluate its effectiveness in advanced ALK+ NSCLC. ^{1 3 4 6 7}

Who Is on the Research Team?

Vincent Lam, M.D.

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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 chemotherapy in the last 14 days or while on the study vaccine.

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 cancer immunotherapy in the last 28 days.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Oncovir, Inc.

Industry Sponsor

Trials

25

Recruited

680+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

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]

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]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-09873

A Vaccine for the Treatment of Patients with Advanced ALK ... This phase I/II trial evaluates the safety and effectiveness of an anaplastic lymphoma kinase (ALK) peptide vaccine for treating patients with anaplastic ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10620113/

ALKing the flames of lung cancer immunosensitivity - PMC Vaccines based on ALK peptides improved immune response, and when combined with ICIs, this led to a striking improvement in survival in a mouse model of ALK+ ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05950139

Study Details | NCT05950139 | Peptide Vaccine To ... 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.

4. lungevity.org lungevity.org/blogs/innovative-therapeutic-vaccine-for-alk-nsclc-heads-to-phase-1-clinical-trial

Innovative Therapeutic Vaccine for ALK+ NSCLC Heads to ... A therapeutic vaccine that could improve the survival rates for ALK-positive lung cancer patients.

5. mdpi.com mdpi.com/2076-393X/13/2/185

Current Development of Therapeutic Vaccines in Lung ... Clinical findings indicate that this vaccine is associated with a median overall survival (OS) of 14.6 months (95% CI 10.6–18.8) and a progression-free survival ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12229965/

ALK peptide vaccination restores the immunogenicity of ALK ... Here we identified immunogenic ALK peptides to show that ICI induced rejection of ALK+ tumors in the flank but not in the lung. A single peptide vaccination ...

7. careacross.com careacross.com/clinical-trials/trial/NCT05950139

Prophylactic Peptide Vaccine in Advanced ALK+ NSCLC 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.