Pilot Study of Vigil™ + Pembrolizumab for Advanced Melanoma

NCT02574533 | Completed Phase 1 DMC

• 1 other identifier: CL-PTL-123
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open label Pilot study to evaluate the combination of Vigil™ and pembrolizumab in patients with incurable locally advanced or metastatic melanoma. Patients undergoing a standard of care surgical procedure (e.g., tumor biopsy, palliative resection) and meeting procurement eligibility criteria may have tumor harvested for Vigil™ vaccine manufacture. This study evaluates the hypothesis that vaccination with Vigil™ will induce cancer-specific T cell immunity in these patients. Addition of pembrolizumab to Vigil™ treated patients will further augment these immune changes on sequential biopsy when comparing post-Vigil™ but pre-PD-1 inhibitor to post-PD-1 inhibitor biopsies, and the combination therapy will be associated with reduction of tumor volume on clinical exam and/or imaging.

Conditions

Melanoma Recurrent; Malignant Melanoma; Melanoma

Keywords

Immunotherapy; PD-1 inhibitor; Keytruda; checkpoint inhibitor; vaccine; FANG; Vigil

Outcome Measures

Primary Outcomes (1)

• Tumor Immune-Related Response to Vigil and Vigil + Pembrolizumab

  Tumor Immune-Related Response to Vigil and Vigil + Pembrolizumab as measured by Tumor biopsy for Immunohistochemistry

  16 weeks

Secondary Outcomes (2)

• Best Overall Response Rate (ORR) to Vigil and Vigil + Pembrolizumab

  26 weeks

• Toxicities and AEs for Vigil + Pembrolizumab according to the Common Toxicity Criteria for Adverse Events (CTCAE) Version 4.03

  26 weeks

Study Arms (1)

Vigil™ + Pembrolizumab

EXPERIMENTAL

Biological: Vigil™ 1 x 10e7 cells via intradermal injection on Day 1, 15, 29, 43 and then every 3 weeks thereafter for a minimum of 4 administrations and a maximum of 9 administrations (depending on the quantity of Vigil™ manufactured from surgical specimens. Drug: Pembrolizumab 2mg/kg by intravenous infusion over 30 minute starting on day 43 and every 3 weeks thereafter

Biological: Vigil; Drug: Pembrolizumab

Interventions

Vigil BIOLOGICAL

Vigil™ 1 x 10e7 cells via intradermal injection on Day 1, 15, 29, 43 and then every 3 weeks thereafter for a minimum of 4 administrations and a maximum of 9 administrations (depending on the quantity of Vigil™ manufactured from surgical specimens)

Also known as: formerly known as FANG™, bi-shRNAfurin and GMCSF Autologous Tumor Cell Immunotherapy

Vigil™ + Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab 2mg/kg by intravenous infusion over 30 minute starting on day 43 and every 3 weeks thereafter

Also known as: Keytruda®, PD-1 inhibitor

Vigil™ + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients will be eligible for tissue procurement for the Vigil™ manufacturing process, if they meet all of the following criteria:
• Age ≥ 18 years.
• ECOG Performance Status ≤ 1
• Estimated survival ≥ 6 months.
• If activating BRAF mutation present, subject has previously received BRAF and/or MEK inhibitor
• Planned standard of care surgical procedure (e.g., tumor biopsy or palliative resection or thoracentesis) and expected availability of a cumulative mass of \~10-30 grams tissue ("golf-ball" size) for vaccine manufacture. Tissue obtained for vaccine manufacture must not have been previously irradiated.
• At least one area of cancer that is not intended for resection or vaccine manufacture and in the opinion of the investigator is appropriate for serial biopsy.
• Ability to understand and the willingness to sign a written informed consent document for tissue harvest.

You may not qualify if:

• Patients meeting any of the following criteria are not eligible for tissue procurement for the Vigil™ manufacturing:
• Documented history of tumor PD-L1 expression positivity (defined as membranous staining of neoplastic cells \>1%)
• Anti-cancer chemotherapy, immunotherapy, or biologic therapy within 3 weeks or radiation therapy within 1 week prior to procurement of tumor for vaccine manufacture.
• Radiation therapy treatment of lesion intended for vaccine manufacture unless post-radiation progression of that lesion is confirmed.
• Medical condition requiring any form of chronic systemic immunosuppressive therapy (steroid or other) except physiologic replacement doses of hydrocortisone or equivalent (no more than 30 mg hydrocortisone or 10 mg prednisone equivalent daily) for \< 30 days duration
• Known history of other malignancy unless having undergone curative intent therapy without evidence of that disease for ≥ 3 years except cutaneous squamous cell and basal cell skin cancer, superficial bladder cancer, in situ cervical cancer or other in situ cancers are allowed if definitively resected.
• Brain metastases unless treated with curative intent (gamma knife or surgical resection) and without evidence of progression for ≥ 2 months.
• Any documented history of autoimmune disease with exception of Type 1 diabetes on stable insulin regimen, hypothyroidism on stable dose of replacement thyroid medication, vitiligo, or asthma not requiring systemic steroids.
• Known history of allergies or sensitivities to gentamicin.
• History of or current evidence of any condition (including medical, psychiatric or substance abuse disorder), therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
• Known HIV or chronic Hepatitis B or C infection.
• History of pneumonitis or interstitial lung disease.
• Successful manufacturing of at least 4 vials of Vigil™.
• ECOG performance status (PS) ≤ 1
• Estimated survival ≥ 4 months.

Sponsors & Collaborators

• Gradalis, Inc.: lead

Study Sites (3)

Texas Oncology P.A., Texas Cancer Center

Abilene, Texas, 79606, United States

Location

Mary Crowley Medical Research Centers

Dallas, Texas, 75230, United States

Location

Cancer Care Northwest

Spokane, Washington, 99202, United States

Location

Related Publications (4)

• Nemunaitis J, Barve M, Orr D, Kuhn J, Magee M, Lamont J, Bedell C, Wallraven G, Pappen BO, Roth A, Horvath S, Nemunaitis D, Kumar P, Maples PB, Senzer N. Summary of bi-shRNA/GM-CSF augmented autologous tumor cell immunotherapy (FANG) in advanced cancer of the liver. Oncology. 2014;87(1):21-9. doi: 10.1159/000360993. Epub 2014 Jun 25.

  PMID: 24968881 BACKGROUND

• Senzer N, Barve M, Kuhn J, Melnyk A, Beitsch P, Lazar M, Lifshitz S, Magee M, Oh J, Mill SW, Bedell C, Higgs C, Kumar P, Yu Y, Norvell F, Phalon C, Taquet N, Rao DD, Wang Z, Jay CM, Pappen BO, Wallraven G, Brunicardi FC, Shanahan DM, Maples PB, Nemunaitis J. Phase I trial of "bi-shRNAi(furin)/GMCSF DNA/autologous tumor cell" vaccine (FANG) in advanced cancer. Mol Ther. 2012 Mar;20(3):679-86. doi: 10.1038/mt.2011.269. Epub 2011 Dec 20.

  PMID: 22186789 BACKGROUND

• Ghisoli M, Barve M, Mennel R, Lenarsky C, Horvath S, Wallraven G, Pappen BO, Whiting S, Rao D, Senzer N, Nemunaitis J. Three-year Follow up of GMCSF/bi-shRNA(furin) DNA-transfected Autologous Tumor Immunotherapy (Vigil) in Metastatic Advanced Ewing's Sarcoma. Mol Ther. 2016 Aug;24(8):1478-83. doi: 10.1038/mt.2016.86. Epub 2016 Apr 25.

  PMID: 27109631 BACKGROUND

• Ghisoli M, Barve M, Schneider R, Mennel R, Lenarsky C, Wallraven G, Pappen BO, LaNoue J, Kumar P, Nemunaitis D, Roth A, Nemunaitis J, Whiting S, Senzer N, Fletcher FA, Nemunaitis J. Pilot Trial of FANG Immunotherapy in Ewing's Sarcoma. Mol Ther. 2015 Jun;23(6):1103-1109. doi: 10.1038/mt.2015.43. Epub 2015 Mar 19.

  PMID: 25917459 BACKGROUND

MeSH Terms

Conditions

Melanoma

Interventions

FANG vaccine; pembrolizumab; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Luisa Manning, MD

  Gradalis, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2015
• First Posted: October 14, 2015
• Study Start: October 1, 2015
• Primary Completion: September 1, 2017
• Study Completion: September 1, 2017
• Last Updated: September 27, 2017

Record last verified: 2017-09

Locations

US (3)