A Trial of FANG™ Vaccine for Participants With Ovarian Cancer

NCT01309230 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CL-PTL 105
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 7

Brief Summary

This was a clinical trial for women with ovarian cancer scheduled to have an operation to remove the cancerous tissue. The cancer cells removed during the planned surgery were used to attempt to make the investigational product, named Vigil. Vigil is considered an immunotherapy. In this study, participants who met the requirements to be in the study and if Vigil was successfully made from the participants cancer cells, participants underwent treatment with their standard chemotherapy regimen. At the end of the standard chemotherapy regimen and if there was no evidence of remaining cancer, participants were randomly assigned to receive the Vigil or would be assigned to the standard of care group, which in this study meant no further treatment was given to the participant. The purpose of this study was to compare the difference between the participants who received Vigil versus the usual care after completion of standard chemotherapy and to determine if Vigil delayed or prevented ovarian cancer from coming back.

Conditions

Ovarian Cancer

Keywords

Stage III; Stage IV; epithelial ovarian cancer; ovarian cancer; Adjuvant bi-shRNAfurin and GMCSF; immunotherapy; Vigil; FANG; Autologous Tumor Cell Vaccine

Outcome Measures

Primary Outcomes (1)

• Time to Recurrence (TTR)

  Time to recurrence is the time to progression by Radiological Tumor Assessment by local investigators using the Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1. Disease recurrence was defined as the appearance of any measurable or evaluable lesion or as asymptomatic CA-125 levels \>35 U/mL at two consecutive measurements, at least one month apart.

  Treatment start to the date of first recurrence or date of death if the participant died before recurrence. Radiographic assessment at baseline, </= 1 week prior to Cycle 4, at Standard of Care intervals, and when CA-125>35 U/mL, approximately 3 years.

Secondary Outcomes (3)

• Number of Participants Positive for T-cell and Immune Activation Markers

  Blood was collected at tissue procurement, prior to the 1st and 3rd cycles of chemotherapy post debulking, at screening, months 2, 4, 6, end of treatment, and quarterly until recurrence, up to 3 years.

• Predictive Potential of Tumor Infiltrating Lymphocyte (TIL) and Tumor Associated Macrophage (TAM) Phenotypes

  From tissue procurement until recurrence.

• Vigil Related Adverse Events (AEs)

  From first dose of Vigil until 30 days following last dose of Vigil, up to 13 months.

Study Arms (2)

Group A (Vigil™)

EXPERIMENTAL

Vigil immunotherapy was administered at a concentration of at 1 x 10e7 cells/injection via intradermal injection for a minimum of 4 doses and a maximum of 12 doses starting ≥3 weeks following completion of chemotherapy (no longer than 2.5 months post chemotherapy). Participants were treated monthly for up to 12 months as long as sufficient Vigil was available and the participant was clinically stable.

Biological: Vigil™

Group B (Observational - Standard of Care)

NO INTERVENTION

Participants received standard of care without maintenance therapy.

Interventions

Vigil™ BIOLOGICAL

Vigil is composed of autologous tumor cells harvested from the patient at the time of initial de-bulking surgery which are then transfected extracorporeally, with a plasmid encoding for the gene for GM-CSF, an immune-stimulatory cytokine, and a bifunctional, short hairpin RNA which specifically knocks down the expression of furin, the critical convertase responsible for production of the two TGβ isoforms.

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

Group A (Vigil™)

Eligibility Criteria

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

You may qualify if:

• Patients were eligible for tissue procurement for the Vigil™ vaccine manufacturing process if they met all of the following criteria:
• Presumptive Stage III/IV papillary serous or endometrioid ovarian cancer.
• Per Amendment #8, treatment naïve, high risk ovarian cancer was no longer be stratified, but the following information was collected:
• Stage IV or suboptimal (\>1 cm residual) Stage III disease versus Stage III patients with optimal (≤1 cm residual) disease,
• CA-125 ≤10 U/ml versus CA-125 greater than 10 but less than or equal to 20 U/ml
• IP chemotherapy versus IV chemotherapy
• Availability of "golf-ball" size 10-30 grams tissue at time of primary surgical debulking.
• ECOG performance status (PS) 0-2 prior to tumor debulking laparotomy
• Ability to understand and the willingness to sign a written informed consent document for tissue harvest.

You may not qualify if:

• Patients who met any of the following criteria were not eligible for tissue procurement for the Vigil manufacturing:
• 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 were 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 HIV or chronic Hepatitis B or C infection.
• 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 was not in the best interest of the patient to participate, in the opinion of the treating Investigator.
• Histologically confirmed Stage III/IV papillary serous or endometrioid ovarian cancer.
• Clinically defined CR (no cancer related symptoms, normal physical examination and CT scan abdomen/pelvis and CXR, and CA-125 ≤20 U/ml) following completion of primary surgical debulking. Patients enrolled must have completed at least 5 but no more than 6 cycles platinum/taxane adjuvant or interval debulking and chemotherapy (or chemotherapy as per recommendations of NCCN guidelines, category 1 (IP chemotherapy included)). (Patients who completed surgery/chemotherapy with a CA-125 \>20 U/mL pre-registration had the option of being followed up to 2 months if serial CA-125 values continued to decrease at a rate of CA-125 decrease of ≥ 50% per month.)
• Successful manufacturing of 4 vials of Vigil™ vaccine
• Recovered from all clinically relevant toxicities related to prior protocol specific therapies (including neuropathy to ≤Grade 2).
• ECOG performance status (PS) 0-1.
• Normal organ and marrow function as defined below:
• Absolute granulocyte count ≥ 1,500/mm3 Absolute lymphocyte count ≥ 200/mm3 Platelets ≥ 75,000/mm3 Total bilirubin ≤ 2 mg/dL AST(SGOT)/ALT(SGPT) ≤ 2x institutional upper limit of normal Creatinine \< 1.5 mg/dL

Sponsors & Collaborators

• Gradalis, Inc.: lead

Study Sites (7)

Florida Cancer Specialists

West Palm Beach, Florida, 33401, United States

Location

Dartmouth-Hitchcock Medical Center/Norris Cotton Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Mary Crowley Cancer Research Centers

Dallas, Texas, 75230, United States

Location

Texas Oncology - Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Texas Oncology - Fort Worth

Fort Worth, Texas, 76104, United States

Location

Cancer Care Northwest

Spokane, Washington, 99202, United States

Location

Related Publications (9)

• 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

• 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

• 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

• Ghisoli M, Rutledge M, Stephens PJ, Mennel R, Barve M, Manley M, Oliai BR, Murphy KM, Manning L, Gutierrez B, Rangadass P, Walker A, Wang Z, Rao D, Adams N, Wallraven G, Senzer N, Nemunaitis J. Case Report: Immune-mediated Complete Response in a Patient With Recurrent Advanced Ewing Sarcoma (EWS) After Vigil Immunotherapy. J Pediatr Hematol Oncol. 2017 May;39(4):e183-e186. doi: 10.1097/MPH.0000000000000822.

  PMID: 28338569 BACKGROUND

• Rocconi RP, Grosen EA, Ghamande SA, Chan JK, Barve MA, Oh J, Tewari D, Morris PC, Stevens EE, Bottsford-Miller JN, Tang M, Aaron P, Stanbery L, Horvath S, Wallraven G, Bognar E, Manning L, Nemunaitis J, Shanahan D, Slomovitz BM, Herzog TJ, Monk BJ, Coleman RL. Gemogenovatucel-T (Vigil) immunotherapy as maintenance in frontline stage III/IV ovarian cancer (VITAL): a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Oncol. 2020 Dec;21(12):1661-1672. doi: 10.1016/S1470-2045(20)30533-7.

  PMID: 33271095 BACKGROUND

• Oh J, Barve M, Matthews CM, Koon EC, Heffernan TP, Fine B, Grosen E, Bergman MK, Fleming EL, DeMars LR, West L, Spitz DL, Goodman H, Hancock KC, Wallraven G, Kumar P, Bognar E, Manning L, Pappen BO, Adams N, Senzer N, Nemunaitis J. Phase II study of Vigil(R) DNA engineered immunotherapy as maintenance in advanced stage ovarian cancer. Gynecol Oncol. 2016 Dec;143(3):504-510. doi: 10.1016/j.ygyno.2016.09.018. Epub 2016 Sep 24.

  PMID: 27678295 RESULT

• Oh J, Barve M, Senzer N, Aaron P, Manning L, Wallraven G, Bognar E, Stanbery L, Horvath S, Manley M, Nemunaitis J, Walter A, Rocconi RP. Long-term follow-up of Phase 2A trial results involving advanced ovarian cancer patients treated with Vigil(R) in frontline maintenance. Gynecol Oncol Rep. 2020 Sep 17;34:100648. doi: 10.1016/j.gore.2020.100648. eCollection 2020 Nov. No abstract available.

  PMID: 33364285 RESULT

• Rocconi RP, Stanbery L, Madeira da Silva L, Barrington RA, Aaron P, Manning L, Horvath S, Wallraven G, Bognar E, Walter A, Nemunaitis J. Long-Term Follow-Up of Gemogenovatucel-T (Vigil) Survival and Molecular Signals of Immune Response in Recurrent Ovarian Cancer. Vaccines (Basel). 2021 Aug 12;9(8):894. doi: 10.3390/vaccines9080894.

  PMID: 34452019 RESULT

MeSH Terms

Conditions

Ovarian Neoplasms; Carcinoma, Ovarian Epithelial

Interventions

FANG vaccine

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: Clinical and Regulatory Operations
• Organization: Gradalis, Inc.

info@gradalisinc.com

214-442-8100

Study Officials

• John Nemunaitis, MD

  Gradalis, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

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

Model Details: Participants were randomized 2 (Group A (Vigil)):1 (Group B (Standard of Care)). Randomization was only applicable to participants enrolled prior to approval of Protocol Amendment 8, dated June 19, 2014. All participants enrolled after approval of Protocol Amendment 8 were assigned to Group A (Vigil).

Study Record Dates

• First Submitted: February 25, 2011
• First Posted: March 7, 2011
• Study Start: March 8, 2011
• Primary Completion: February 2, 2022
• Study Completion: February 2, 2022
• Last Updated: June 8, 2025
• Results First Posted: March 24, 2023

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)