Clinical Trials /

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

NCT03743298

Description:

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. These will be patients who have either never received treatment for metastatic melanoma or were previously treated with enzymatic inhibitors of the BRAF/MEK pathway because of BRAF600E/K mutations, and are about to initiate anti-PD1 monotherapy. The intent is to treat 14 to 20 patients with the combination of anti-PD-1 and AV-MEL-1.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety of AV-MEL-1 With Anti-PD-1 Therapy in Metastatic Melanoma
  • Official Title: Phase 1B Trial of AV-MEL-1 (Autologous Dendritic Cells Loaded With Autologous Tumor Antigens) With Anti-PD-1 Checkpoint Inhibitors in Metastatic Melanoma

Clinical Trial IDs

  • ORG STUDY ID: CL-MEL-P01-US
  • NCT ID: NCT03743298

Conditions

  • Metastatic Melanoma

Interventions

DrugSynonymsArms
AV-MEL-1AV-MEL-1

Purpose

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. These will be patients who have either never received treatment for metastatic melanoma or were previously treated with enzymatic inhibitors of the BRAF/MEK pathway because of BRAF600E/K mutations, and are about to initiate anti-PD1 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, performance of
           leukapheresis, and intended plan to treat with a standard anti-PD-1 regimen, and to
           treat with their patient-specific AV-MEL-1 once it has been manufactured.

        2. Prior to starting anti-PD-1 therapy, 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.

        3. Prior to starting anti-PD-1 therapy, patients will undergo leukapheresis to obtain
           peripheral blood mononuclear cells that will be converted into dendritic cells (DC).

        4. Patients will initiate anti-PD-1 therapy monotherapy (e.g. pembrolizumab or nivolumab)
           using standard doses and schedules of administration.

        5. When the vaccine is ready, which will take approximately 8 weeks from the date of tumor
           resection, and the patient has had the opportunity to have received about two months of
           anti-PD-1 monotherapy, it is expected per standard of care that the patient will undergo
           radiographic assessment to classify disease status and response (if there was measurable
           disease at baseline) to the anti-PD-1 therapy.

        6. Starting week 10, 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.

        7. 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.
    

Trial Arms

NameTypeDescriptionInterventions
AV-MEL-1ExperimentalAV-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.
  • AV-MEL-1

Eligibility Criteria

        Inclusion Criteria:

          -  Age > 18

          -  Karnofsky Performance Status (KPS) of > 70

          -  Histologic diagnosis of metastatic melanoma

          -  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)

          -  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 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

          -  Previous anti-cancer treatment for melanoma, other than BRAF/MEK inhibittion.

          -  Known hypersensitivity to GM-CSF

          -  Pregnancy
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Aivita Biomedical, Inc.

Last Updated

April 2, 2021