NeoVax + CDX-301 + Nivolumab for Melanoma

Recruiting at 1 trial location

Overseen By Patrick A Ott, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Immunosuppressants, Anti-cancer agents

Disqualifiers: Active brain metastases, Autoimmune disease, HIV, 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

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for melanoma, a type of skin cancer. Researchers are testing a personalized vaccine called NeoVax, combined with other drugs—CDX-301, an immune system booster, and either Nivolumab or Pembrolizumab, both immunotherapy drugs—to determine if they can help the immune system fight cancer. People with stage IIIB/C/D or stage IV cutaneous melanoma that is resectable, unresectable, or has been surgically removed might be suitable candidates. Participants must have previously collected tumor tissue available for analysis. As a Phase 1 trial, this 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 requires that you do not take any anti-cancer agents, investigational anti-cancer therapies, or immunosuppressive agents within six months of participating. If you are on such medications, you may need to stop them before joining the trial.

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

Previous studies have led to FDA approval of Nivolumab and Pembrolizumab for treating melanoma, indicating their safety for this condition is well understood. Nivolumab, for instance, is generally well tolerated as an additional treatment after the main one and has shown promising results in improving survival rates with fewer side effects.

For new treatments like NeoVax and CDX-301, less information is available about their safety because they remain in early testing stages. This part of the study focuses on determining if these treatments can be safely used together. It is important to note that this is an early phase trial, which typically involves assessing the safety of treatments in humans.

Overall, while confidence exists in the safety of Nivolumab and Pembrolizumab, NeoVax and CDX-301 are still under careful study to ensure their safety when combined with other drugs. Participants in the trial will help researchers gather crucial safety information. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of NeoVax, CDX-301, and Nivolumab for melanoma because it offers a tailored approach that differs from standard treatments like surgery, radiation, and chemotherapy. NeoVax is personalized; it uses a vaccine made from the patient’s own tumor tissue, which could enhance the immune system’s ability to target cancer cells specifically. CDX-301 is a growth factor that boosts the production of dendritic cells, key players in immune response, potentially increasing the effectiveness of the vaccine. Meanwhile, Nivolumab, an immune checkpoint inhibitor, helps the immune system recognize and attack cancer cells more effectively. This combination aims to create a more precise and robust immune response against melanoma compared to traditional treatments.

What evidence suggests that this trial's treatments could be effective for melanoma?

Research has shown that Nivolumab and Pembrolizumab, two drugs in this trial, have received FDA approval for treating melanoma, a type of skin cancer. This approval indicates their proven effectiveness for this condition. In this trial, participants in one arm will receive Nivolumab, which benefits about 25% of melanoma patients, meaning roughly one in four people experience a positive effect.

NeoVax is a new vaccine designed to target specific changes in cancer cells. It is used with CDX-301, which may enhance the immune system's response to the vaccine. Although researchers are still learning about NeoVax and CDX-301, using them with well-known drugs like Nivolumab or Pembrolizumab in separate arms of this trial appears promising. ^{3 4 6 7 8}

Who Is on the Research Team?

Patrick Ott, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Adults with stage IIIB/C/D or IV melanoma that's resectable or unresected, and not mucosal/uveal type. Must have good performance status, normal organ/marrow function, no severe allergies to study drugs, no HIV/AIDS or hepatitis B/C infection. Women must test negative for pregnancy and agree to contraception; men also need to use contraception.

Inclusion Criteria

Participant is willing and able to give written informed consent

I am not breastfeeding if I decide to participate in this study.

I agree to use contraception during and for 7 months after the study.

Exclusion Criteria

I have an autoimmune disease but it's either mild or under control.

You have been diagnosed with HIV or AIDS.

Any underlying medical condition, psychiatric condition or social situation that in the opinion of the investigator would compromise study administration as per protocol or compromise the assessment of AEs

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NeoVax in combination with CDX-301 and either Nivolumab or Pembrolizumab. Nivolumab is administered every 4 weeks for up to 2 years, and Pembrolizumab is administered every 3 weeks for 3 doses followed by every 6 weeks for 15 doses.

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• CDX-301
• NEOVAX
• Nivolumab

Trial Overview The trial is testing a combination of NeoVax (a personalized cancer vaccine), CDX-301, and Nivolumab against melanoma. Participants will receive these drugs to see if they work better together in treating the disease compared to current standard treatments.

How Is the Trial Designed?

Group I: CDX-301 + Neovax + Pembrolizumab Experimental Treatment 3 Interventions

* Participants will have vaccine made from tissue collected from tumor biopsy, or from previously collected archival biopsy or surgical tissue. * Participants will receive neoadjuvant Pembrolizumab for 3 doses every 3 weeks, then undergo standard-of-care surgical resection. * Participants will receive adjuvant NeoVax and CDX-301. CDX-301 will be administered at a predetermined dose, dependent on the number of participants previously enrolled, for 5 days starting 2 days before the initiation of NeoVax. CDX-301 will then be administered at a predetermined dose dependent on the number of participants previously enrolled 2 days before and for 5 days coinciding with the administration of NeoVax on days 50 and 78. * Participants will receive adjuvant Pembrolizumab for 15 doses every 6 weeks.

Group II: CDX-301 + Neovax + Nivolumab Experimental Treatment 3 Interventions

* Participants will have vaccine made from tissue collected from metastatic tumor biopsy or surgical resection, or from previously collected archival biopsy or surgical tissue. * Participants will receive Nivolumab at a flat dose every 4 weeks up to two years. * Participants will receive CDX-301 at a predetermined dose dependent on the number of participants previously enrolled for 5 days starting 2 days before the initiation of NeoVax. CDX-301 will then be administered at a predetermined dose dependent on the number of participants previously enrolled 2 days before and for 5 days coinciding with the administration of NeoVax on days 50 and 78.

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Celldex Therapeutics

Industry Sponsor

Trials

66

Recruited

5,900+

Anthony S. Marucci

Celldex Therapeutics

Chief Executive Officer since 2008

MBA from Columbia University, MHL from Brown University

Diane C. Young

Celldex Therapeutics

Chief Medical Officer since 2019

MD from Harvard Medical School, AB in Biochemical Sciences from Harvard University

Published Research Related to This Trial

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 proof-of-principle study involving three patients with advanced melanoma, personalized vaccines targeting unique tumor neoantigens successfully triggered strong and diverse T-cell responses.

The personalized vaccines were well tolerated by the patients, indicating a favorable safety profile for this innovative treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Customizing vaccines for melanoma. [2015]

In a phase 2 study of 23 patients with high-risk resectable melanoma, the combination of ipilimumab and nivolumab showed high response rates (73% overall response rate and 45% pathologic complete response) but also resulted in significant toxicity, with 73% of patients experiencing grade 3 treatment-related adverse events.

Nivolumab monotherapy had lower response rates (25% overall response rate and 25% pathologic complete response) but was associated with much lower toxicity (only 8% grade 3 treatment-related adverse events), suggesting that while combination therapy is effective, it comes with higher risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma. Amaria, RN., Reddy, SM., Tawbi, HA., et al.[2021]

A vaccine targeting tumor neoantigens was tested in patients with metastatic melanoma, non-small cell lung cancer, and bladder cancer, showing improved progression-free survival compared to historical controls.

The vaccine effectively stimulated tumor-specific T cells, suggesting it may enhance the effectiveness of nivolumab, a common cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccine Increases PFS for Metastatic Tumors. [2020]

A personalized neoantigen nanovaccine combined with anti-PD-1 antibody treatment led to a significant clinical benefit in an advanced pancreatic cancer patient, resulting in an overall survival of 10.5 months after treatment.

The treatment successfully induced a robust T cell response against multiple vaccine peptides, indicating that this approach may effectively enhance immune responses in controlling progressive metastatic pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced Pancreatic Cancer Patient Benefit From Personalized Neoantigen Nanovaccine Based Immunotherapy: A Case Report. Shao, J., Liu, Q., Shen, J., et al.[2023]

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]

The KEYNOTE-D36 trial is a phase II study designed to evaluate the safety and effectiveness of the personalized neoepitope vaccine EVX-01 combined with pembrolizumab in patients with unresectable or metastatic melanoma who have not previously received checkpoint inhibitor therapy.

The primary goal of the trial is to determine if EVX-01 can enhance the overall response rate in patients who initially show stable disease or a partial response to pembrolizumab, providing critical data before advancing to larger phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KEYNOTE - D36: personalized immunotherapy with a neoepitope vaccine, EVX-01 and pembrolizumab in advanced melanoma. Long, GV., Ferrucci, PF., Khattak, A., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, shows strong antitumor activity but is associated with immune-related adverse events that can affect patient safety and treatment continuation, necessitating careful monitoring.

Long-term safety data, including a 5-year follow-up, suggests that nivolumab can be safely administered to various challenging patient subgroups, but identifying biomarkers for severe toxicity could improve patient selection for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on the safety of nivolumab for the treatment of advanced melanoma. Czarnecka, AM., Rutkowski, P.[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]

In a phase 3 trial involving 405 patients with advanced melanoma, nivolumab resulted in a significantly higher objective response rate (31.7%) compared to investigator's choice of chemotherapy (10.6%), indicating its superior efficacy as a treatment option.

Nivolumab was associated with fewer severe adverse effects compared to chemotherapy, with only 5% of patients experiencing serious drug-related side effects, suggesting it is a safer alternative for patients who have progressed after previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Weber, JS., D'Angelo, SP., Minor, D., et al.[2022]

In the phase III CheckMate 238 trial, 67.7% of patients receiving nivolumab experienced treatment-related adverse events (TRAEs), with the most common being pruritus and diarrhea, primarily occurring within the first 3 months of treatment.

Despite the high incidence of TRAEs, there was no significant association found between these adverse events and recurrence-free survival (RFS), indicating that the safety profile of nivolumab remains consistent and does not negatively impact long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant nivolumab for stage III/IV melanoma: evaluation of safety outcomes and association with recurrence-free survival. Mandala, M., Larkin, J., Ascierto, PA., et al.[2022]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04930783

NCT04930783 | NeoVax + CDX-301 and Nivolumab or ... The FDA has approved Nivolumab and Pembrolizumab as a treatment option for melanoma. It is known that melanoma cancers have mutations (changes in genetic ...

2. dana-farber.org dana-farber.org/clinical-trials/21-066

A Phase Ib study of NeoVax in combination with CDX-301 ... This research study is studying the drugs called NeoVax (a new type of personalized neoantigen vaccine) in combination with CDX-301 and Nivolumab or ...

3. withpower.com withpower.com/trial/phase-1-melanoma-10-2021-0fb05

NeoVax + CDX-301 + Nivolumab for Melanoma Nivolumab monotherapy had lower response rates (25% overall response rate and 25% pathologic complete response) but was associated with much lower toxicity ( ...

4. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/293082

NeoVax + CDX-301 and Nivolumab or Pembrolizumab in ... This research study is studying the drugs called NeoVax (a new type of personalized neoantigen vaccine) in combination with CDX-301 and Nivolumab or ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04930783/neovax-cdx-301-and-nivolumab-or-pembrolizumab-in-melanoma

NeoVax + CDX-301 and Nivolumab or Pembrolizumab in ... The study will also be determining what the appropriate dose of CDX-301 to be given in combination with NeoVax and Nivolumab or Pembrolizumab.

6. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT04930783?recrs=abc&cond=%22Melanoma%22&draw=2&rank=4

NeoVax + CDX-301 and Nivolumab or Pembrolizumab in ... The purpose of this Phase I study is to determine if it is possible to safely administer a personalized neoantigen vaccine (NeoVax) in combination with the ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04930783

NCT04930783 | NeoVax + CDX-301 and Nivolumab or ... The FDA has approved Nivolumab and Pembrolizumab as a treatment option for melanoma. It is known that melanoma cancers have mutations (changes in genetic ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4620684/

PMC Search Update Conclusions. Nivolumab with vaccine is well tolerated as adjuvant therapy and demonstrates immunologic activity with promising survival in high-risk resected ...