Personalized Cancer Vaccine + Pembrolizumab for Lymphocytic Leukemia

Recruiting at 1 trial location

Overseen By Oriol Olive Noguer

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Immunosuppressants, Corticosteroids, Antivirals, others

Disqualifiers: Autoimmune disease, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 1 year

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new personalized cancer vaccine called NeoVax, possibly combined with other treatments like cyclophosphamide and pembrolizumab, to help treat chronic lymphocytic leukemia (CLL). Researchers aim to determine if this approach can effectively target and control CLL, a type of blood cancer. Suitable candidates for this trial have untreated CLL and a high white blood cell count.

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 does not specify if you need to stop taking your current medications. However, you cannot be on immunosuppressive or immunomodulatory agents, chronic systemic corticosteroids, or any investigational agents. If you have been using corticosteroids, they must be tapered off at least one week before starting the trial.

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

Research shows that NeoVax, a personalized cancer vaccine, is generally well-tolerated. Early trial results for this type of vaccine indicate safety and initial success in treating patients, meaning most can receive the vaccine without serious issues.

When combined with a low dose of cyclophosphamide, NeoVax maintains its encouraging safety profile. Cyclophosphamide, a common chemotherapy drug, is given in much smaller amounts in this study, which is expected to reduce side effects.

Adding pembrolizumab, an FDA-approved drug for other cancers, enhances the treatment. Pembrolizumab helps the immune system fight cancer more effectively. Research suggests that combining personalized cancer vaccines with pembrolizumab may boost the immune response without significant safety concerns.

Overall, previous research indicates that the combination treatments in the study seem safe. However, since this study is in its early stages, these findings are preliminary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for lymphocytic leukemia, like chemotherapy and targeted therapies, work by directly attacking cancer cells. But NeoVax, a personalized cancer vaccine, works differently. It is designed to train the immune system to recognize and fight cancer cells more effectively. Researchers are excited about NeoVax because it is tailored to each patient's unique tumor, potentially leading to a more precise and effective response. When combined with pembrolizumab, an immunotherapy drug, and low-dose cyclophosphamide, which helps modulate the immune response, this approach could offer a novel, personalized strategy for tackling leukemia.

What evidence suggests that this trial's treatments could be effective for chronic lymphocytic leukemia?

Research shows that personalized neoantigen vaccines, such as NeoVax, help the immune system specifically target cancer cells. Early results from similar studies indicate that these vaccines are generally safe and show initial signs of effectiveness. NeoVax trains the immune system to identify and attack cancer cells, offering promise for people with chronic lymphocytic leukemia (CLL).

In this trial, some participants will receive NeoVax alone, while others will receive NeoVax combined with low-dose cyclophosphamide, a drug that enhances the immune system's ability to fight cancer. Another group will receive NeoVax with both low-dose cyclophosphamide and pembrolizumab. Pembrolizumab, already used for other cancer types, may enhance the effect by blocking a pathway that cancer cells use to evade the immune system, allowing it to detect and combat the cancer. Although specific data on these combinations for CLL remains limited, the components have shown promise in related research. ^{1 2 3 4 5}

Who Is on the Research Team?

Inhye Ahn

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 with untreated chronic lymphocytic leukemia (CLL) that has an unmutated IGHV gene and no history of CLL-directed therapy. Participants must not expect to need treatment within six months, have measurable disease, normal organ/marrow function, and agree to use effective contraception or abstain from sexual activity. Excluded are those with prior CLL therapies, autoimmune diseases, large lymph nodes, certain genetic mutations in CLL cells, rapid disease progression, low immunoglobulin levels or active infections.

Inclusion Criteria

My CLL has a specific genetic feature with less than 2% mutation.

I have had at least two blood tests for lymphocytes since my CLL diagnosis.

I have been diagnosed with CLL according to the 2018 guidelines.

Exclusion Criteria

I am HIV-positive and on combination antiretroviral therapy.

I have received treatment for CLL within the last 2 years.

I am not on long-term steroids or drugs that affect my immune system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the NeoVax vaccine in a priming and booster phase, with priming shots on days 1, 4, 8, 15, and 22, and booster shots on days 78 and 134. Low-dose cyclophosphamide is administered twice daily on weeks -2, 1, 3, 5. Pembrolizumab is administered starting on Week 12 Day 78 for up to 17 cycles.

Approximately 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• NeoVax
• Pembrolizumab

Trial Overview The study tests a personalized Neoantigen Vaccine (NeoVax) combined with Poly-ICLC and Cyclophosphamide against Pembrolizumab for treating CLL. The vaccine aims to stimulate the patient's immune system specifically against their cancer cells by using unique markers found on their tumor.

How Is the Trial Designed?

Group I: Neovax + Low-dose cyclophosphamide + Pembrolizumab Experimental Treatment 3 Interventions

* NeoVax will be administered in a priming and booster phase. * The priming shots will comprise days 1, 4, 8, 15, and 22. * Booster shots will be given on days 78 and 134. * Low dose cyclophosphamide is administered twice daily on weeks -2, 1, 3, 5 * Pembrolizumab will be administered starting on Week 12 Day 78 and for up to 17 cycles (approximately 1 year).

Group II: Neovax + Low-dose cyclophosphamide Experimental Treatment 2 Interventions

* NeoVax will be administered in a priming and booster phase. * The priming shots will comprise days 1, 4, 8, 15, and 22. * Booster shots will be given on days 78 and 134. * Low dose cyclophosphamide is administered twice daily on weeks -2, 1, 3, 5

Group III: NeoVax Experimental Treatment 1 Intervention

* NeoVax will be administered in a priming and booster phase. * The priming shots will comprise days 1, 4, 8, 15, and 22. * Booster shots will be given on days 78 and 134.

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

BioNTech SE

Industry Sponsor

Trials

84

Recruited

120,000+

Prof. Dr. Ugur Sahin

BioNTech SE

Chief Executive Officer since 2008

MD from University of Cologne

Prof. Özlem Türeci

BioNTech SE

Chief Medical Officer since 2018

MD from Saarland University

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Oncovir, Inc.

Industry Sponsor

Trials

25

Recruited

680+

Published Research Related to This Trial

Neoantigens, which are unique to each patient's tumor due to specific mutations, serve as promising targets for personalized cancer vaccines, potentially leading to more effective treatments.

Clinical trials have shown that neoantigen-targeting vaccines, especially when combined with checkpoint blockade therapies, can elicit strong T-cell responses and produce significant antitumor effects in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized neoantigen vaccines: A new approach to cancer immunotherapy. Aldous, AR., Dong, JZ.[2021]

Personalized neoantigen-enhanced oncolytic adenoviruses, specifically MY-NEOVAX™, showed positive therapeutic effects in two heavily pretreated end-stage cancer patients, indicating potential for improved treatment outcomes.

Both patients experienced treatment benefits lasting over 12 months without significant toxicities or serious adverse events, along with documented stabilization of their tumors and improved overall health status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended treatment with MY-NEOVAX, personalized neoantigen-enhanced oncolytic viruses, for two end-stage cancer patients. Bouvet, M., Reid, TR., Larson, C., et al.[2020]

The personalized neoantigen-based vaccine NEO-PV-01, combined with PD-1 blockade, was found to be safe in a phase Ib trial involving 82 patients with advanced melanoma, lung, or bladder cancer, with no serious treatment-related adverse events reported.

The vaccine successfully induced strong CD4+ and CD8+ T cell responses, which not only targeted the specific neoantigens but also led to an immune response against additional neoantigens, indicating a broadening of the immune attack on the tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell Lung Cancer, or Bladder Cancer. Ott, PA., Hu-Lieskovan, S., Chmielowski, B., et al.[2023]

In a Phase Ib clinical trial involving 38 patients with advanced non-squamous non-small cell lung cancer, the personalized neoantigen vaccine NEO-PV-01 combined with standard chemotherapy and pembrolizumab showed no serious treatment-related adverse events, indicating a favorable safety profile.

The treatment elicited strong immune responses, including the activation of neoantigen-specific CD4+ and CD8+ T cells, and demonstrated correlations between immune parameters and clinical responses, suggesting that the vaccine effectively stimulates the immune system against tumor mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized neoantigen vaccine NEO-PV-01 with chemotherapy and anti-PD-1 as first-line treatment for non-squamous non-small cell lung cancer. Awad, MM., Govindan, R., Balogh, KN., et al.[2022]

In a phase Ib trial, a personalized cancer vaccine combined with the PD-L1 inhibitor atezolizumab demonstrated the ability to induce specific T-cell responses against neoantigens in patients with solid cancers.

This combination therapy resulted in complete or partial tumor eradication in some patients, indicating its potential efficacy in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Personalized Vaccine Induces Antitumor Activity. [2021]

Personalized neoantigen vaccines are a promising new approach in cancer immunotherapy, designed to stimulate T cell responses specifically against tumor-specific neoantigens unique to individual patients.

Initial clinical studies have shown that these vaccines can generate strong immune responses and exhibit preliminary antitumor activity, particularly in melanoma and other cancers, thanks to advancements in sequencing and bioinformatics technologies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the development of personalized neoantigen-based therapeutic cancer vaccines. Blass, E., Ott, PA.[2023]

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]

The study developed neoantigen minigene (NAM) vaccine vectors that showed strong immune responses and complete protection against tumors in mice, indicating their potential efficacy as personalized cancer vaccines.

The research established that high-affinity neoantigens drive immunogenicity, and a poly-specific vaccine vector is crucial for effective tumor protection, suggesting a clear pathway for clinical application in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poly-specific neoantigen-targeted cancer vaccines delay patient derived tumor growth. Aurisicchio, L., Salvatori, E., Lione, L., et al.[2020]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03219450

A Personalized Neoantigen Cancer Vaccine in Treatment ... Study Overview. Brief Summary. This research study is studying a novel type of CLL vaccine as a possible treatment for chronic lymphocytic leukemia ...

2. healthtree.org healthtree.org/cll/community/articles/personalized-cll-vaccine-neovax-inhye-ahn-md

A Personalized CLL Vaccine: NeoVax How Effective is NeoVax? Although there is not yet published data about NeoVax's efficacy for CLL as the study is in its early stages, the ...

3. dana-farber.org dana-farber.org/research/integrative-research/cancer-vaccines/neovax

NeoVax Cancer Vaccine This vaccine is administered to the corresponding patient with the goal of stimulating the immune system to specifically attack their cancer.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11427492/

Personalized neoantigen cancer vaccines In our review, early data of neoantigen vaccines trials confirmed the acceptable safety profile and preliminary clinical efficacy (Table 2) as the later line ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0092867425006853

A multi-adjuvant personal neoantigen vaccine generates ... Personalized neoantigen-targeting vaccines have demonstrated great promise; however, improved immunogenicity is still needed. Since antigen availability and ...