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

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Melanoma
• Intervention / Treatment: Drug: 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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jim Langford; Phone Number: 949-872-2555; Email: jim@aivitabiomedical.com

Study Locations

• United States
  • California
    • Irvine, California, United States, 92618
      • Recruiting
      • Jericho Rabago
      • Principal Investigator: Chaitali S Nangia, MD
    • Newport Beach, California, United States, 92663
      • Recruiting
      • Hoag Memorial Hospital Presbyterian
      • Principal Investigator: Chaitali S Nangia, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age > 18
• Karnofsky Performance Status (KPS) of > 70
• Presence of at least one metastatic lesion that is to be removed surgically as part of standard care (e.g. diagnosis or diagnostic testing, mono- or oligometastatic disease, alleviation of symptoms etc)
• • Diagnosis of metastatic melanoma with at least one lesion that is amenable for surgical resection per standard of care (e.g. diagnosis or diagnostic testing, mono- or oligometastatic disease, alleviation of symptoms etc)
• Considered appropriate for standard anti-PD1 antibody monotherapy by managing physician
• Given written informed consent to participate in the study

Exclusion Criteria:

• Known to have active hepatitis B or C or HIV (need not be screened)
• KPS of < 70; see Appendix A
• Known underlying cardiac disease associated with myocardial dysfunction that requires active medical treatment, or unstable angina related to atherosclerotic cardiovascular disease, or under treatment for arterial or venous peripheral vascular disease
• Diagnosis of any other invasive cancer or other disease process which is considered to be life-threatening within the next five years, and/or taking anti-cancer therapy for cancer other than melanoma
• Active infection that could be eminently life-threatening or other active medical condition that could be eminently life-threatening, including active blood clotting or bleeding diathesis.
• Known autoimmune disease, immunodeficiency, or disease process that involves the chronic or intermittent use of immunosuppressive therapy
• Uncontrolled brain or spinal cord metastases or active leptomingeal metastatic disease.
• Received another investigational drug within 28 days of the first dose or are planning to receive another investigational drug while receiving this investigational treatment
• Known hypersensitivity to GM-CSF
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Safety Endpoint: Number of grade 3-5 adverse events with AV-MEL-1 + PD-1 versus PD-1 alone	Determine whether combining AV-MEL-1 with anti-PD-1 is associated with increased risk as defined by AEs per NCI common toxicity criteria	3 years

Collaborators and Investigators

• Sponsor: Aivita Biomedical, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2021
• Primary Completion (Anticipated): May 1, 2024
• Study Completion (Anticipated): May 1, 2026

Study Registration Dates

• First Submitted: November 13, 2018
• First Submitted That Met QC Criteria: November 15, 2018
• First Posted (Actual): November 16, 2018

Study Record Updates

• Last Update Posted (Actual): April 10, 2023
• Last Update Submitted That Met QC Criteria: April 7, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: CL-MEL-P01-US

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No