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

• Sponsor: Aivita Biomedical, Inc.
• Information provided by (Responsible Party): Aivita Biomedical, Inc.

Study Description

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. 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.

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, 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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	20 participants
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
Estimated Study Start Date :	June 2019
Estimated Primary Completion Date :	June 2020
Estimated Study Completion Date :	January 2023

Arms and Interventions

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.

Outcome Measures

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

Eligibility Criteria

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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
• 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

Contacts and Locations

Contacts

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Contact: Candace Hsieh, PhD	949-872-2555 ext 110	candace@aivitabiomedical.com

Sponsors and Collaborators

Aivita Biomedical, Inc.

Investigators

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Study Chair:	Robert O Dillman, MD	Aivita Biomedical, Inc.

More Information

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Responsible Party:	Aivita Biomedical, Inc.
ClinicalTrials.gov Identifier:	NCT03743298 History of Changes
Other Study ID Numbers:	CL-MEL-P01-US
First Posted:	November 16, 2018
Last Update Posted:	January 7, 2019
Last Verified:	January 2019

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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; Sargramostim; Immunologic Factors; Physiological Effects of Drugs