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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03743298
Recruitment Status : Recruiting
First Posted : November 16, 2018
Last Update Posted : April 10, 2023
Sponsor:
Information provided by (Responsible Party):
Aivita Biomedical, Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
Metastatic Melanoma Drug: AV-MEL-1 Phase 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 21, 2021
Estimated Primary Completion Date : May 2024
Estimated Study Completion Date : May 2026

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

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.




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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03743298


Contacts
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Contact: Jim Langford 949-872-2555 jim@aivitabiomedical.com

Locations
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United States, California
Jericho Rabago Recruiting
Irvine, California, United States, 92618
Contact: Jericho Rabago, BSN, RN    949-764-6796    jericho.rabago@hoag.org   
Principal Investigator: Chaitali S Nangia, MD         
Hoag Memorial Hospital Presbyterian Recruiting
Newport Beach, California, United States, 92663
Contact: Jericho Rabago, BSN, RN    949-764-6796    jericho.rabago@hoag.org   
Principal Investigator: Chaitali S Nangia, MD         
Sponsors and Collaborators
Aivita Biomedical, Inc.
Investigators
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Study Chair: Robert O Dillman, MD Aivita Biomedical, Inc.
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Responsible Party: Aivita Biomedical, Inc.
ClinicalTrials.gov Identifier: NCT03743298    
Other Study ID Numbers: CL-MEL-P01-US
First Posted: November 16, 2018    Key Record Dates
Last Update Posted: April 10, 2023
Last Verified: April 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas