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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and potential effectiveness of a new treatment for metastatic melanoma, a type of skin cancer that has spread to other parts of the body. It combines a new treatment, AV-MEL-1, with an existing drug, anti-PD-1, which helps the immune system attack cancer cells. The study seeks participants diagnosed with metastatic melanoma who have a tumor that can be surgically removed as part of their standard care. Eligible participants are those starting anti-PD-1 treatment and either have not received any previous treatment or have tried certain treatments before.

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 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.

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

Research has shown that AV-MEL-1, a treatment using a patient's own immune cells loaded with cancer markers, has been tested before. In a previous study, over 95% of the attempts to create these cell cultures succeeded, indicating a strong track record for producing the vaccine.

Another study found that this treatment was safe and even helped patients live longer compared to a different vaccine tested. In Chile, similar treatments have been tested on people with advanced melanoma (a type of skin cancer) and were well-tolerated.

Since this trial is in an early phase, it focuses mainly on safety. The new treatment has passed initial safety checks but is still under close observation for any side effects. Overall, based on previous studies, the treatment appears promising in terms of safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for melanoma, which often include immune checkpoint inhibitors like anti-PD-1 therapies, AV-MEL-1 offers a unique approach by using autologous dendritic cells loaded with autologous tumor antigens (ATA). This means the treatment is personalized, as it utilizes the patient’s own tumor cells to stimulate an immune response, potentially enhancing the body’s ability to fight cancer. Researchers are excited because this method could provide a more targeted and effective immune response, offering hope for improved outcomes in melanoma treatment.

What evidence suggests that AV-MEL-1 combined with anti-PD-1 might be an effective treatment for melanoma?

Research has shown that AV-MEL-1, which participants in this trial will receive, might be a promising treatment for melanoma. This treatment uses special immune cells from the patient's own body, prepared to help the immune system recognize and attack cancer cells. In earlier studies, over 95% of patients produced these cells, indicating potential for effective treatment. Another study found that patients with advanced melanoma lived longer when treated with similar vaccines. While more research is needed, these early results suggest AV-MEL-1 could effectively treat melanoma. ^{1 5 6 7 8}

Who Is on the Research Team?

Robert O Dillman, MD

Principal Investigator

Aivita Biomedical, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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]

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]

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]

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]

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 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]

Citations

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Autologous dendritic cells loaded with antigens from self ... Key observations include: [1] greater than 95% success rates for tumor cell cultures and monocyte collection for dendritic cell production; [2] injections are ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37133853/

Autologous dendritic cells loaded with antigens from self- ... Key observations include: [1] greater than 95% success rates for tumor cell cultures and monocyte collection for dendritic cell production; [2] ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01875653

Study Details | NCT01875653 | Autologous Dendritic Cell- ... This research study is evaluating if a patient-specific experimental therapy for metastatic melanoma will lengthen survival with minimal harmful effects.

4. tandfonline.com tandfonline.com/doi/full/10.2217/mmt-2018-0010

Patient-Specific Dendritic Cell Vaccines with Autologous ... Overall survival for all 72 melanoma patients treated with autologous dendritic cell vaccines loaded with autologous tumor antigens and survival in a single arm ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1465324910704382

Vaccination with autologous dendritic cells pulsed ... In this clinical study we tested the safety and efficacy of vaccination with mature antigen-pulsed DC in 46 patients with metastatic MM.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06152367

Immunization With Autologous Dendritic Cells and Tumor ... In Chile, this study constitutes the first phase I clinical trial for treating advanced malignant melanoma using dendritic cell vaccines loaded with allogeneic ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6688559/

Patient-specific dendritic cell vaccines with autologous ... A randomized Phase II trial confirmed safety and longer survival compared with an autologous tumor cell vaccine (TCV) consisting of irradiated autologous tumor ...

8. aacrjournals.org aacrjournals.org/cancerres/article/80/16_Supplement/6536/644617/Abstract-6536-Safety-and-efficacy-of-autologous

Abstract 6536: Safety and efficacy of autologous tumor lysate ... The autologous tumor lysate, particle loaded, dendritic cell (TLPLDC) vaccine utilizes the whole antigenic panel of the patient's tumor to ...