AV-MEL-1 + Anti-PD-1 for Melanoma
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
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
Trial Summary
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.
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.12345
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.678910
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.15111213
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.
See 3 more
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.
See 7 more
Trial 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 (Cancer Vaccine)
Trial OverviewThe 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
1Treatment groups
Experimental Treatment
Group I: AV-MEL-1Experimental Treatment1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Hoag Hospital - IrvineIrvine, CA
Jericho RabagoIrvine, CA
Hoag Memorial Hospital PresbyterianNewport Beach, CA
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Who Is Running the Clinical Trial?
Aivita Biomedical, Inc.Lead Sponsor
References
Serum lactate dehydrogenase as an early marker for outcome in patients treated with anti-PD-1 therapy in metastatic melanoma. [2022]Treatment with programmed death receptor-1 (PD-1) antibodies is associated with high response rates in patients with advanced melanoma. Reliable markers for early response and outcome are still sparse.
Nodular primary cutaneous melanoma is associated with PD-L1 expression. [2023]In previous studies, patients with Stage III melanomas expressing PD-L1 in more than 5% of their neoplastic cells had improved recurrence-free survival with anti-PD1 adjuvant therapy.
Programmed Death-Ligand 1 Expression and Response to the Anti-Programmed Death 1 Antibody Pembrolizumab in Melanoma. [2022]Purpose Expression of programmed death-ligand 1 (PD-L1) is a potential predictive marker for response and outcome after treatment with anti-programmed death 1 (PD-1). This study explored the relationship between anti-PD-1 activity and PD-L1 expression in patients with advanced melanoma who were treated with pembrolizumab in the phase Ib KEYNOTE-001 study (clinical trial information: NCT01295827). Patients and Methods Six hundred fifty-five patients received pembrolizumab10 mg/kg once every 2 weeks or once every 3 weeks, or 2 mg/kg once every 3 weeks. Tumor response was assessed every 12 weeks per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by independent central review. Primary outcome was objective response rate. Secondary outcomes included progression-free survival (PFS) and overall survival (OS). Membranous PD-L1 expression in tumor and tumor-associated immune cells was assessed by a clinical trial immunohistochemistry assay (22C3 antibody) and scored on a unique melanoma (MEL) scale of 0 to 5 by one of three pathologists who were blinded to clinical outcome; a score ≥ 2 (membranous staining in ≥ 1% of cells) was considered positive. Results Of 451 patients with evaluable PD-L1 expression, 344 (76%) had PD-L1-positive tumors. Demographic and staging variables were equally distributed among PD-L1-positive and -negative patients. An association between higher MEL score and higher response rate and longer PFS (hazard ratio, 0.76; 95% CI, 0.71 to 0.82) and OS (hazard ratio, 0.76; 95% CI, 0.69 to 0.83) was observed ( P
Prognostic and Clinicopathological Value of PD-L1 in Melanoma: A Meta-Analysis. [2020]There is a growing interest in using programmed death ligand-1 (PD-L1) as a prognostic marker for melanoma. We conducted this meta-analysis to explore the prognostic and clinicopathological value of PD-L1 in melanoma.
Association of Pembrolizumab With Tumor Response and Survival Among Patients With Advanced Melanoma. [2022]The programmed death 1 (PD-1) pathway limits immune responses to melanoma and can be blocked with the humanized anti-PD-1 monoclonal antibody pembrolizumab.
Cardiovascular Immunotoxicity Associated with Immune Checkpoint Inhibitors in Metastatic Melanoma. [2023]Checkpoint inhibitors, such as PD-1 inhibitors (nivolumab, pembrolizumab) and anti-CTLA-4 (CD152) (ipilimumab), are widely used in metastatic melanoma, and most immune-related adverse events are known. Several cardiovascular AEs (CVAEs) associated with immune checkpoint inhibitor exposure have been reported in post-marketing surveillance studies and represent major issues for patients with melanoma during and after cancer treatment. Data on CVAES induced by immune checkpoint inhibitors in melanoma, especially incidence and risk factors, are lacking.
Immune-related adverse events correlate with improved survival in patients undergoing anti-PD1 immunotherapy for metastatic melanoma. [2022]Therapeutic chances for metastatic melanoma have consistently changed over the last years with the advent of antibodies targeting the programmed cell death protein-1 (PD-1). Onset of immune-related adverse events (irAEs) during treatment can be a source of concern, and the association with survival outcome is yet to be defined.
Comparative Risks of High-Grade Adverse Events Among FDA-Approved Systemic Therapies in Advanced Melanoma: Systematic Review and Network Meta-Analysis. [2020]Background: Head-to-head evidence is lacking in comparative risks of high-grade adverse events (AEs) among different systemic treatment options for advanced melanoma. Methods: An up-to-date systematic review and network meta-analysis (NMA) was performed. Randomized controlled trials (RCTs) of patients with advanced melanoma were eligible if at least one intervention was the Food and Drug Administration-approved targeted or immune checkpoint inhibitors. Risks of high-grade AEs were estimated by random-effects Bayesian NMAs, based on relative risks. Surface under the cumulative ranking probabilities was used to assess relative ranking of treatments. The summary incidences were calculated. Results: Twenty-five RCTs (12,925 patients) comparing 10 different systemic treatment options were included. BRAF/MEK had the highest risk of overall high-grade AEs (pooled incidence: 32.11%). BRAF had the highest risk of high-grade arthralgia (0.39%), whereas MEK had the highest risk of high-grade hypertension (2.28%) and nausea (0.37%). Cytotoxic T-lymphocyte antigen 4 (CTLA-4)/chemo had the highest risk of high-grade diarrhea (1.31%), alanine aminotransferase (0.60%), and aspartate aminotransferase elevation (0.59%). Programmed cell death 1 (PD-1)/CTLA-4 had the highest risks of high-grade pyrexia (1.14%) and rash (0.94%). Using PD-1 inhibitor alone had the lowest risks of overall high-grade AEs. Conclusions: Different systemic treatment options have varying high-grade AEs in advanced melanoma treatment. Current evidences highlight the important risks of BRAF/MEK, CTLA-4/chemo, and PD-1/CTLA-4.
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]Programmed death 1 protein (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors are promising cancer immunotherapy. Their dermatologic safety profiles are still poorly understood. The purpose of this article is to evaluate the incidence of selected dermatologic and mucosal adverse effects (AEs) and determine the risk of developing these adverse events associated with PD-1/PD-L1 inhibitors, compared with chemotherapy or ipilimumab.
The safety of anti PD-1 therapeutics for the treatment of melanoma. [2018]The introduction of immunotherapies into clinical practice has substantially improved the prognosis of metastatic melanoma patients as well as patients suffering from other cancers. The two FDA-approved checkpoint inhibitors against PD-1 (nivolumab and pembrolizumab) have been shown to significantly improve patient survival while being less toxic than previous treatment options. Areas covered: The current scientific literature on safety and adverse events (AEs) related to anti-PD-1 therapies has been investigated with special attention to case reports and to the latest results announced at the major clinical cancer and melanoma meetings, including ASCO (American Society of Clinical Oncology), ESMO (European Society of medical Oncology) and EADO (European Association of Dermato-Oncology) annual meetings. Expert opinion: Even though anti-PD-1 therapies are better tolerated than conventional chemo- or other immune-therapies, they still induce a plethora of AEs. Given the mechanism of action, it is supposed that most if not all of them are immune related. Fortunately, the majority are mild and manageable. However, due to the increase in patients' life expectancy, there is a substantial need to understand and prevent severe cutaneous, pulmonary, neurological and other AEs which have major impact on the quality of life. The safety profile after long term use of these medications is still unclear. In addition, non-steroid based immune interventions to control autoimmunity are still to be developed.
PD-1 expression on Melan-A-reactive T cells increases during progression to metastatic disease. [2020]Programmed death 1 (PD-1) is known as an important factor for the development of tolerogenicity. This has been proven in chronic viral infections and different tumor models. To address the role of PD-1 and its ligand programmed death ligand 1 (PD-L1) in different stages of malignant melanoma, we investigated peripheral blood and tumor tissues in regard to overall survival (OS) and prognostic relevance. One hundred samples of peripheral blood mononuclear cells from HLA-A2(+) patients with malignant melanoma (Stages I-IV) were analyzed in seven color FACS combined with multimer analyses for the immunodominant epitope of Melan-A (peptide A2/Melan-A(p26-35mod) ). Corresponding formalin-fixed paraffin-embedded tissues of primary tumor and distant organ metastases from 37 cases were analyzed by immunohistochemistry for Melan-A, PD-L1 and PD-1 expression. Compared to the total CD8(+) T cell population, PD-1 expression by A2/Melan-A(+) CD8(+) T cells was over-represented in melanoma stages III and IV (p
Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. [2022]Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, disrupts PD-1-mediated signaling and may restore antitumor immunity.
Patients with Desmoplastic Melanoma May Respond to PD-1 Blockade. [2019]PD-1 blockade achieved responses in 70% of patients with desmoplastic melanoma in a retrospective analysis.