Vigil™ + Nivolumab in Advanced Non-Small Cell Lung Cancer

NCT02639234 | Withdrawn Phase 2

• 1 other identifier: CL-PTL-122
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open label phase 2 study to evaluate the combination of Vigil™ and nivolumab in advanced or metastatic NSCLC that is progressive on or after one prior platinum-based systemic therapy. Patients meeting study eligibility criteria will receive Vigil™ every 2 weeks (for a minimum of 4 and a maximum of 12 doses) and nivolumab every 2 weeks. The combination of Vigil™ and nivolumab will demonstrate a higher objective response rate (ORR) than the historical ORR of single agent nivolumab in patients with advanced NSCLC.

Conditions

Advanced Non-small Cell Lung Cancer; Metastatic Non-small Cell Lung Cancer; Lung Neoplasms

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) by RECIST 1.1 criteria of Vigil™ plus nivolumab in patients with NSCLC after failure of prior platinum-based chemotherapy

  The primary endpoint of ORR is defined as a best response of complete remission (CR) or partial remission (PR) according to RECIST 1.1 as determined by the investigator.

  12 months

Secondary Outcomes (2)

• Tolerability and safety profile of Vigil™ combined with nivolumab (all adverse events (CTCAE 4.03), laboratory safety assessments, and physical examination findings)

  12 months

• Progression-Free Survival (PFS) of study patients treated with Vigil™ and nivolumab

  12 months

Study Arms (1)

Vigil™ + Nivolumab

EXPERIMENTAL

Patients meeting study eligibility criteria will receive doublet therapy comprising of (i) Vigil™ 1 x 10\^7 cells by intradermal injection every 2 weeks (for a minimum of 4 and a maximum of 12 doses) and (ii) nivolumab 3 mg/kg by intravenous infusion over 60 minutes every 2 weeks.

Biological: Vigil™; Drug: Nivolumab

Interventions

Vigil™ BIOLOGICAL

Upon completion of nivolumab infusion, subjects will receive Vigil™, 1.0 x 10\^7cells via intradermal injection on Day 1 every 14 days for a minimum of 4 and a maximum of 12 doses depending on quantity of Vigil™ manufactured from surgical specimens.

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

Vigil™ + Nivolumab

Nivolumab DRUG

Prior to Vigil™, subjects will receive nivolumab 3 mg/kg by intravenous infusion over 60 minutes on Day 1 every 14 days. If nivolumab is administered beyond 12 months it will be administered off study.

Also known as: PD-1/PD-L1 checkpoint inhibitor, Opdivo

Vigil™ + Nivolumab

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:
• Histologically or cytologically confirmed diagnosis of NSCLC.
• Age ≥ 18 years.
• Locally advanced or metastatic disease that is progressive after one prior platinum-based systemic chemotherapy regimen
• Adjuvant therapy will count as a line of therapy if administered within 6 months of relapse).
• Subjects with EGFR or ALK mutations should also have received appropriate targeted therapy.
• No systemic therapy, immunologic therapy or investigational therapy within 3 weeks and no radiation therapy within 1 week prior to tumor procurement for vaccine manufacture.
• 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) or pleural fluid estimated volume ≥ 500mL (must be primary tap) for immunotherapy manufacture.
• At least one area of cancer, not intended for vaccine manufacture, that is measureable by RECIST 1.1 criteria.
• At least one tumor, not intended for vaccine manufacture, that is considered appropriate for on-treatment biopsy. The same tumor may suffice for both on-treatment biopsy and RECIST 1.1 measurement so long as imaging occurs prior to biopsy.
• ECOG Performance Status ≤ 1
• Estimated survival ≥ 6 months.
• 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:
• Any localized anticancer therapy (e.g., radiation, radiofrequency ablation, cryotherapy) to tumor intended for vaccine manufacture unless unequivocal evidence of post-treatment disease progression of the target tumor.
• 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 ≥ 4 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 ≤ 1
• Estimated survival ≥ 4 months.
• Disease that is measurable by RECIST 1.1 criteria.
• Adequate organ function as defined by the following laboratory values:

Sponsors & Collaborators

• Gradalis, Inc.: lead

Study Sites (3)

Texas Oncology, P.A., Texas Cancer Center

Abilene, Texas, 79606, United States

Location

Mary Crowley Cancer Research Centers

Dallas, Texas, 75230, United States

Location

Cancer Care Northwest

Spokane Valley, Washington, 99216, United States

Location

Related Publications (4)

• 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

• 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

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

FANG vaccine; Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Luisa Manning, MD

  Gradalis, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2015
• First Posted: December 24, 2015
• Study Start: March 1, 2016
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: July 31, 2017

Record last verified: 2017-07

Locations

US (3)