NCT03743298

Safety of AV-MEL-1 With Anti-PD-1 Therapy in Metastatic Melanoma

Phase 1B Trial of AV-MEL-1 (Autologous Dendritic Cells Loaded With Autologous Tumor Antigens) With Anti-PD-1 Checkpoint Inhibitors in Metastatic Melanoma

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Aivita Biomedical, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is an open label, single-arm, phase IB treatment study to determine the safety of administering anti-PD1 monoclonal antibodies with AV-MEL-1 and to get some suggestion of efficacy, in patients with measurable metastatic melanoma. The study is open to patients who have either never received treatment for metastatic melanoma or were previously treated with anti-PD-1 with or without anti-CTLA-4 or with enzymatic inhibitors of the BRAF/MEK pathway because of BRAF600E/K mutations, and are about to initiate anti-PD-1 monotherapy. The intent is to treat 14 to 20 patients with the combination of anti-PD-1 and AV-MEL-1.

Detailed description

The sequence is as follows: 1. Patients will provide consent for collection of blood and tumor, willingness to undergo leukapheresis, and intended plan to treat with a standard anti-PD-1 monotherapy regimen, and to treat with their patient-specific AV-MEL-1 once it has been manufactured. 2. Prior to starting anti-PD-1 therapy 1. Surgically resected tumor tissue will be sent to AIVITA Biomedical where it will be processed to establish a short-term cell line of autologous tumor cells. Approximately 1 cm3 of surgically excised tumor is preferred. Whenever possible the tissue should be obtained from a lesion no greater than 2 cm in longest diameter. Part of the sample should be assessed by pathologists to confirm melanoma and to test for PDL-1 expression. 2. Patients will undergo leukapheresis to obtain PBMC that will be converted into dendritic cells (DC). 3. Patients who did not have a PET/CT or CT scan performed within the previous 6 weeks, will undergo a PET/CT or CT to define baseline disease status (measurable disease, non-measurable detectable disease, or no evidence of disease). 3. Patients will initiate anti-PD-1 therapy monotherapy (e.g. pembrolizumab or nivolumab) using standard doses and schedules of administration at week 0. 4. When the vaccine is ready, (approximately week 8 or 9) and the patient has had the opportunity to have received about two months of anti-PD-1 monotherapy, 1. The patient will undergo radiographic assessment (PET/CT or CT) to classify disease status (measurable disease, non-measurable detectable disease, or no evidence of disease) and response (if there was measurable disease at baseline) to the anti-PD-1 therapy. 2. AV-MEL-1 will be given concurrently with continuation of the anti-PD-1 therapy. AV-MEL-1 injections will be given weekly for 3 weeks, (weeks 10-12, then monthly at weeks 16, 20, 24, 28, and 32). Blood will be collected from patients prior to each injection for immune monitoring tests. The timing of AV-MEL-1 injections is not synchronized with the administration of anti-PD-1, but they can be administered on the same day. 5. If anti-PD-1 therapy is discontinued during vaccine treatment, the remaining vaccine doses may still be administered at the discretion of the patient's managing physician.

Conditions

• Metastatic Melanoma

Interventions

Type	Name	Description
DRUG	AV-MEL-1	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.

Timeline

• Start date: 2021-04-21
• Primary completion: 2024-05-01
• Completion: 2026-05-01
• First posted: 2018-11-16
• Last updated: 2023-04-10

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study