AV-MEL-1 + Anti-PD-1 for Melanoma

Recruiting at 2 trial locations

Overseen By Jim Langford

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Aivita Biomedical, Inc.

Must be taking: Anti-PD1

Must not be taking: Immunosuppressants, Anti-cancer

Disqualifiers: Hepatitis, HIV, Cardiac disease, others

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

Compensation: Varies

Number of Visits: 1

20 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, if you are taking another investigational drug, you must stop it at least 28 days before starting this trial.

What data supports the effectiveness of the drug AV-MEL-1 + Anti-PD-1 for treating melanoma?

Research shows that anti-PD-1 therapies, like pembrolizumab, are effective in treating advanced melanoma, with higher response rates and longer survival in patients whose tumors express PD-L1. This suggests that combining AV-MEL-1 with anti-PD-1 could potentially enhance treatment effectiveness. ^{1 2 3 4 5}

What is known about the safety of AV-MEL-1 + Anti-PD-1 treatment for melanoma?

Anti-PD-1 therapies, like nivolumab and pembrolizumab, are generally less toxic than older treatments for melanoma, but they can still cause various side effects, most of which are mild and manageable. However, some serious side effects affecting the skin, lungs, and nerves can occur, and their long-term safety is not fully understood. ^{6 7 8 9 10}

What makes the AV-MEL-1 + Anti-PD-1 treatment unique for melanoma?

The AV-MEL-1 + Anti-PD-1 treatment is unique because it combines a novel component, AV-MEL-1, with an anti-PD-1 drug, which blocks a pathway that usually limits the immune system's ability to attack melanoma. This combination aims to enhance the immune response against melanoma cells, potentially improving outcomes compared to using anti-PD-1 therapy alone. ^{1 5 11 12 13}

What is the purpose of this trial?

This trial tests a combination of an immune-boosting drug and a personalized vaccine in patients with advanced melanoma. The goal is to see if this approach is safe and effective in helping the immune system fight cancer. Ipilimumab, an immune-boosting drug, has been shown to improve survival in advanced melanoma patients, but only about 20% experience long-term benefits.

Research Team

Robert O Dillman, MD

Principal Investigator

Aivita Biomedical, Inc.

Eligibility Criteria

This trial is for adults over 18 with metastatic melanoma, who are fit enough to undergo surgery for at least one lesion and can start anti-PD-1 therapy. They should have a good performance status (able to care for themselves) and not be on any investigational drugs or have serious heart disease, uncontrolled brain metastases, active hepatitis B/C or HIV, another life-threatening cancer, severe infections, bleeding disorders, autoimmune diseases or need immunosuppressive therapy.

Inclusion Criteria

Given written informed consent to participate in the study

I have a cancer spread that will be surgically removed.

My doctor thinks I am a good candidate for anti-PD1 antibody treatment.

Exclusion Criteria

I have an autoimmune disease or need regular immunosuppressive therapy.

I do not have any life-threatening infections or conditions like uncontrolled bleeding.

I do not have uncontrolled brain or spinal cord cancer spread.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pre-Treatment Preparation

Collection of blood and tumor tissue, leukapheresis, and baseline disease status assessment

6 weeks

Multiple visits for procedures

Anti-PD-1 Monotherapy

Patients receive standard doses of anti-PD-1 therapy

8-9 weeks

Regular visits for therapy administration

Combination Treatment

Concurrent administration of AV-MEL-1 with anti-PD-1 therapy, including weekly and monthly injections

24 weeks

Weekly and monthly visits for injections

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Treatment Details

Interventions

• AV-MEL-1

Trial Overview The study tests the safety of AV-MEL-1 combined with anti-PD-1 antibodies in patients with metastatic melanoma. It's an open-label phase IB trial aiming to treat 14-20 patients. Participants may be new to treatment or previously treated with specific inhibitors due to BRAF600E/K mutations.

Participant Groups

Group I: AV-MEL-1 Experimental Treatment 1 Intervention

AV-MEL-1: Autologous dendritic cells loaded with autologous tumor antigens (ATA) from a short-term cell culture of autologous tumor cells. AV-MEL-1 is admixed with granulocyte-macrophage colony stimulating factor (GM-CSF) as an adjuvant, prior to injection.

Who Is Running the Clinical Trial?

Aivita Biomedical, Inc.

Lead Sponsor

Trials

8

Recruited

1,000+

Findings from Research

In a study of 66 patients with advanced melanoma treated with PD-1 antibodies, those with elevated baseline serum lactate dehydrogenase (LDH) had significantly shorter overall survival compared to those with normal LDH levels, indicating that LDH can be a critical prognostic marker.

Changes in LDH levels during treatment were predictive of response; patients with a reduction in LDH were more likely to achieve partial remission, while those with an increase had a shorter overall survival, suggesting LDH could help monitor treatment effectiveness early on.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum lactate dehydrogenase as an early marker for outcome in patients treated with anti-PD-1 therapy in metastatic melanoma. Diem, S., Kasenda, B., Spain, L., et al.[2022]

In a study of 66 patients with invasive primary cutaneous melanomas, PD-L1 expression was found in 21% of samples and was significantly associated with increased melanoma thickness and nodular-type melanoma, suggesting that PD-L1 could be a useful biomarker for this type of cancer.

Nodular-type melanoma was 6.48 times more likely to express PD-L1 compared to other types, indicating that patients with this melanoma subtype may benefit from adjuvant immunotherapy targeting PD-L1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nodular primary cutaneous melanoma is associated with PD-L1 expression. Giavina-Bianchi, M., Giavina-Bianchi, P., Sotto, MN., et al.[2023]

In a study of 655 patients with advanced melanoma treated with pembrolizumab, 76% had PD-L1-positive tumors, and higher PD-L1 expression was associated with better treatment responses and longer progression-free survival (PFS) and overall survival (OS).

Despite the correlation between PD-L1 expression and treatment efficacy, some patients with PD-L1-negative tumors also experienced durable responses, suggesting that PD-L1 status is not the sole predictor of treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Death-Ligand 1 Expression and Response to the Anti-Programmed Death 1 Antibody Pembrolizumab in Melanoma. Daud, AI., Wolchok, JD., Robert, C., et al.[2022]

Positive PD-L1 expression in melanoma is significantly associated with higher levels of tumor-infiltrating lymphocytes (TILs) and is linked to metastatic melanoma, suggesting its role in the immune response to tumors.

In patients with metastatic melanoma, positive PD-L1 expression is associated with prolonged overall survival, indicating it may serve as an important prognostic marker for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic and Clinicopathological Value of PD-L1 in Melanoma: A Meta-Analysis. Xu, J., Wang, F., Yan, Y., et al.[2020]

In a study of 655 patients with advanced melanoma, pembrolizumab showed an overall objective response rate of 33%, indicating its efficacy in treating this type of cancer.

The median overall survival for patients receiving pembrolizumab was 23 months, with a 12-month survival rate of 66%, while 14% of patients experienced severe treatment-related adverse events, highlighting its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma. Ribas, A., Hamid, O., Daud, A., et al.[2022]

Patients with melanoma treated with immune checkpoint inhibitors have a significantly increased risk of dyslipidemia, which can lead to serious cardiovascular issues, with a Peto odds ratio of 4.74 based on data from 3289 patients across five clinical trials.

While other cardiovascular adverse events (CVAEs) like myocarditis and heart failure showed numerical significance, they were not statistically significant compared to other tumors treated with the same inhibitors, indicating a need for careful monitoring of cardiovascular health in melanoma patients undergoing this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular Immunotoxicity Associated with Immune Checkpoint Inhibitors in Metastatic Melanoma. L'Orphelin, JM., Dollalille, C., Akroun, J., et al.[2023]

In a study of 173 patients with metastatic melanoma treated with anti-PD-1 antibodies, 59% experienced immune-related adverse events (irAEs), which were linked to improved progression-free survival (PFS) and overall survival (OS).

Patients who developed vitiligo, a specific type of irAE, showed a trend towards better OS compared to those with other irAEs, suggesting that the occurrence of irAEs may indicate a more favorable response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune-related adverse events correlate with improved survival in patients undergoing anti-PD1 immunotherapy for metastatic melanoma. Indini, A., Di Guardo, L., Cimminiello, C., et al.[2022]

In a systematic review of 25 randomized controlled trials involving 12,925 patients with advanced melanoma, BRAF/MEK treatment was found to have the highest overall risk of high-grade adverse events (AEs) at 32.11%.

Among the treatments, PD-1 inhibitors alone had the lowest risk of high-grade AEs, indicating they may be a safer option compared to other systemic treatments like BRAF/MEK and CTLA-4 combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Risks of High-Grade Adverse Events Among FDA-Approved Systemic Therapies in Advanced Melanoma: Systematic Review and Network Meta-Analysis. Huang, YF., Xie, WJ., Fan, HY., et al.[2020]

In a meta-analysis of 11,465 patients from 18 clinical trials, PD-1/PD-L1 inhibitors were found to significantly increase the risk of developing dermatologic adverse effects like rash and pruritus compared to chemotherapy, with relative risks of 1.84 and 3.74, respectively.

PD-1/PD-L1 inhibitors showed a lower risk of mucosal inflammation and alopecia compared to chemotherapy, indicating a distinct safety profile that differs from traditional cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of dermatologic and mucosal adverse events associated with PD-1/PD-L1 inhibitors in cancer patients: A meta-analysis of randomized controlled trials. Yang, W., Li, S., Yang, Q.[2021]

Immunotherapies, particularly anti-PD-1 checkpoint inhibitors like nivolumab and pembrolizumab, have significantly improved survival rates for metastatic melanoma patients while being less toxic than traditional treatments.

Despite their better tolerability, anti-PD-1 therapies can still cause a range of immune-related adverse events, most of which are mild, but there is a pressing need to understand and manage severe side effects due to the increased life expectancy of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of anti PD-1 therapeutics for the treatment of melanoma. Ramelyte, E., Schindler, SA., Dummer, R.[2018]

In patients with advanced malignant melanoma (Stages III and IV), there is a significant increase in PD-1 expression on Melan-A-specific CD8(+) T cells, indicating a potential role of PD-1 in immune tolerance during later stages of the disease.

Higher expression of PD-L1 on melanoma cells is positively correlated with overall survival, suggesting that targeting PD-1 could be a promising therapeutic strategy for improving outcomes in advanced melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 expression on Melan-A-reactive T cells increases during progression to metastatic disease. Krönig, H., Julia Falchner, K., Odendahl, M., et al.[2020]

In a phase 3 study involving 582 patients with advanced nonsquamous non-small-cell lung cancer (NSCLC), nivolumab significantly improved overall survival compared to docetaxel, with a median survival of 12.2 months versus 9.4 months, respectively.

Nivolumab also had a much lower rate of severe treatment-related adverse events (10%) compared to docetaxel (54%), indicating a better safety profile while maintaining efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. Borghaei, H., Paz-Ares, L., Horn, L., et al.[2022]

In a retrospective analysis, PD-1 blockade treatment showed a remarkable response rate of 70% in patients with desmoplastic melanoma, indicating its potential efficacy for this specific cancer type.

This finding suggests that PD-1 blockade could be a promising therapeutic option for patients suffering from desmoplastic melanoma, although further studies are needed to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patients with Desmoplastic Melanoma May Respond to PD-1 Blockade. [2019]

References

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

Serum lactate dehydrogenase as an early marker for outcome in patients treated with anti-PD-1 therapy in metastatic melanoma. [2022]

2. France pubmed.ncbi.nlm.nih.gov

Nodular primary cutaneous melanoma is associated with PD-L1 expression. [2023]

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

Programmed Death-Ligand 1 Expression and Response to the Anti-Programmed Death 1 Antibody Pembrolizumab in Melanoma. [2022]

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

Prognostic and Clinicopathological Value of PD-L1 in Melanoma: A Meta-Analysis. [2020]

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

Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Cardiovascular Immunotoxicity Associated with Immune Checkpoint Inhibitors in Metastatic Melanoma. [2023]

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

Immune-related adverse events correlate with improved survival in patients undergoing anti-PD1 immunotherapy for metastatic melanoma. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Comparative Risks of High-Grade Adverse Events Among FDA-Approved Systemic Therapies in Advanced Melanoma: Systematic Review and Network Meta-Analysis. [2020]

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

Risk of dermatologic and mucosal adverse events associated with PD-1/PD-L1 inhibitors in cancer patients: A meta-analysis of randomized controlled trials. [2021]

10. England pubmed.ncbi.nlm.nih.gov

The safety of anti PD-1 therapeutics for the treatment of melanoma. [2018]

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

PD-1 expression on Melan-A-reactive T cells increases during progression to metastatic disease. [2020]

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

Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. [2022]

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

Patients with Desmoplastic Melanoma May Respond to PD-1 Blockade. [2019]