A Trial of Atezolizumab and Vigil in Patients With Advanced Gynecological Cancers

NCT03073525 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CL-PTL-126
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 6

Brief Summary

The clinical trial was a companion study to protocol CL-PTL-119 (A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of Vigil Engineered Autologous Tumor Cell Immunotherapy in Subjects with Stage IIIb-IV Ovarian Cancer in Clinical Complete Response following Surgery and Primary Chemotherapy (VITAL) NCT02346747). Participants who had investigational product (Vigil) successfully made but were not eligible to enroll onto the VITAL study or previously randomized to placebo were given the opportunity to participate in this protocol. The main goal of this clinical trial was to determine the safety of combining Vigil therapy with atezolizumab.

Conditions

Advanced Gynecological Cancers; Ovarian Cancer; Cervical Cancer; Uterine Cancer

Keywords

Stage IIIb; Stage IV; Ovarian Cancer; Cervical Cancer; Uterine Cancer; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Number of Treatment-emergent AEs of Vigil + Atezolizumab

  The safety evaluation included Adverse Events (AEs), Adverse Events of Special Interest (AESIs), Serious Adverse Events (SAEs) and changes from baseline in laboratory evaluations, vital signs, electrocardiograms and physical examinations. AEs were graded according to the National Cancer Institute (NCI) CTCAE v4.03 and coded using the Medical Dictionary for Regulatory Activities. Laboratory abnormalities were graded according to the NCI CTCAE v4.03, if applicable.

  AEs reported from first treatment dose and up to 30 days after last treatment, about 12 months.

Secondary Outcomes (4)

• Immune Response Rate

  Up to 30 days after last treatment

• Time to Progression

  From baseline (prior to treatment) up to 3 years

• Radiographic Overall Response Rate (ORR)

  From first dose to end of study treatment (up to 9 months)

• Overall Survival (OS)

  OS will be evaluated from time of randomization up to 37 months following documented disease progression.

Study Arms (4)

Part 1: Vigil + Atezo

EXPERIMENTAL

This was a safety run in and intervention was combined. The first three participants received Vigil immunotherapy at a concentration of 1x10e7 cells/dose given via intradermal injection every 3 weeks for a minimum of 4 doses and a maximum of 12 doses. Atezolizumab was administered at a dose of 1200 mg as an intravenous infusion every 3 weeks. 1 cycle = 21 days.

Biological: Vigil; Drug: Atezolizumab

Part 2: Vigil first then combination Vigil + Atezo

EXPERIMENTAL

After Part 1 participants completed completed combination therapy without dose-limiting toxicity, then Part 2 participants randomized to Vigil first received two cycles of Vigil alone, then Vigil and atezolizumab given in sequence (Vigil administered first, followed 30 minutes later by atezolizumab) Vigil immunotherapy was administered at a concentration of 1 x 10e6 or 1 x 107 cells/dose given via intradermal injection every 3 weeks for a minimum of 4 doses and a maximum of 12 doses. Atezolizumab was administered at a dose of 1200 mg as an intravenous infusion every 3 weeks, with a maximum of 12 doses. When Vigil and atezolizumab was given together, Vigil 1 cycle = 21 days

Biological: Vigil; Drug: Atezolizumab

Part 2: Atezo first then combination of Vigil + Atezo

EXPERIMENTAL

After Part 1 participants completed completed combination therapy without dose-limiting toxicity, then Part 2 participants randomized to atezolizumab first received two cycles of atezolizumab alone, then Vigil and atezolizumab given in sequence (Vigil administered first, followed 30 minutes later by atezolizumab). Vigil immunotherapy was administered at a concentration of 1 x 10e6 or 1 x 107 cells/dose given via intradermal injection every 3 weeks for a minimum of 4 doses and a maximum of 12 doses. Atezolizumab was administered at a dose of 1200 mg as an intravenous infusion every 3 weeks, with a maximum of 12 doses. 1 cycle = 21 days

Biological: Vigil; Drug: Atezolizumab

Part 3: Atezo Only

OTHER

Participants who completed all cycles of Part 2 were pre-approved by the sponsor for inclusion into Part 3. Atezolizumab alone was administered at a dose of 1200 mg as an intravenous infusion every 3 weeks. 1 cycle = 21 days

Drug: Atezolizumab

Interventions

Vigil BIOLOGICAL

The Vigil vaccine is made up of irradiated autologous tumor cells which have been electroporated ex vivo with the Vigil plasmid designed to suppress expression of both the TGFβ1 and TGFβ2 proteins while simultaneously expressing rhGMCSF protein.

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

Part 1: Vigil + Atezo; Part 2: Atezo first then combination of Vigil + Atezo; Part 2: Vigil first then combination Vigil + Atezo

Atezolizumab DRUG

Atezolizumab was prepared and administered at the FDA approved dose and schedule as described in the U.S. Package Insert (USPI). The initial dose was administered over one hour and if well tolerated, subsequent infusions may have been administered over 30 minutes. Atezolizumab in formulation F03 (1200 mg per vial) was administered in 250 mL 0.9% NaCl IV infusion bags and infusion lines equipped with 0.2 μm in-line filters.

Also known as: TECENTRIQ™, MPDL3280A

Part 1: Vigil + Atezo; Part 2: Atezo first then combination of Vigil + Atezo; Part 2: Vigil first then combination Vigil + Atezo; Part 3: Atezo Only

Eligibility Criteria

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

You may qualify if:

• Subjects will be eligible for tissue procurement for the Vigil manufacturing process, if they meet all of the following criteria:
• Histologically confirmed Stage IIIb, IIIc or IV high-grade papillary serous, clear cell, or endometrioid ovarian, fallopian tube or primary peritoneal carcinoma
• Age ≥ 18 years.
• Estimated survival ≥ 6 months.
• ECOG Performance Status ≤ 1
• Metastatic disease
• Planned standard of care surgical procedure (e.g., tumor biopsy or palliative resection or thoracentesis) and expected availability of a cumulative soft-tissue mass of \~10-30 grams tissue ("grape" to "golf-ball" size) or ascites fluid estimated volume ≥ 500mL (from a primary or secondary paracentesis, yielding in a high volume of tumor cells) for immunotherapy manufacture.
• Tumor intended for immunotherapy manufacture is not embedded in bone and does not contain luminal tissue (e.g. bowel, ureter, bile duct).
• Ability to understand and the willingness to sign a written informed protocol specific consent for tissue harvest or a parental/guardian informed consent and pediatric assent when appropriate.

You may not qualify if:

• Subjects meeting any of the following criteria are 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 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 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 is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
• Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) less than 21 days prior to tissue procurement.
• Successful manufacturing of at least 4 vials of Vigil.
• One of the following:
• Failure to meet the eligibililty criteria for Protocol CL-PTL-119 due to i) histology of ovarian cancer and failure to achieve a complete clinical response following primary debulking surgery and standard paclitaxel/carboplatin therapy OR, ii) a histologic diagnosis of another gynecologic malignancy which is not ovarian cancer.
• Recurrent ovarian cancer.
• Randomized on Protocol CL-PTL-119 and were subsequently unblinded at recurrence and were assigned to the placebo arm.
• ECOG performance status (PS) ≤ 1 (or ≤ 2 due to carcinoid syndrome).

Sponsors & Collaborators

• Gradalis, Inc.: lead
• Roche-Genentech: collaborator

Study Sites (6)

University of South Alabama Mitchell Cancer Institute

Mobile, Alabama, 36604, United States

Location

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Billings Clinic

Billings, Montana, 59101, United States

Location

Dartmouth-Hitchcock Medical Center/ Norris Cotton Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

Prisma Health Cancer Institute

Greenville, South Carolina, 29605, United States

Location

Related Publications (10)

• 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

• Senzer N, Barve M, Nemunaitis J, Kuhn J, Melnyk A, et al. (2013) Long Term Follow Up: Phase I Trial of "Bi-Shrnafurin/GMCSF DNA/Autologous Tumor Cell" Immunotherapy (FANG™) in Advanced Cancer. J Vaccines Vaccin 4:209. doi:10.4172/2157-7560.1000209

  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, 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 BACKGROUND

• Rocconi RP, Monk BJ, Walter A, Herzog TJ, Galanis E, Manning L, Bognar E, Wallraven G, Stanbery L, Aaron P, Senzer N, Coleman RL, Nemunaitis J. Gemogenovatucel-T (Vigil) immunotherapy demonstrates clinical benefit in homologous recombination proficient (HRP) ovarian cancer. Gynecol Oncol. 2021 Jun;161(3):676-680. doi: 10.1016/j.ygyno.2021.03.009. Epub 2021 Mar 11.

  PMID: 33715892 BACKGROUND

• Rodney Paul Rocconi, Erin E. Stevens, Justin N. Bottsford-Miller, Sharad A. Ghamande, Phylicia Aaron, Gladice Wallraven, Ernest Bognar, Meghan Manley, Staci Horvath, Luisa Manning, John J. Nemunaitis, Thomas J Herzog, Bradley J. Monk, Robert L. Coleman, and Vigil Team (2020), A phase I combination study of vigil and atezolizumab in recurrent/refractory advanced-stage ovarian cancer: Efficacy assessment in BRCA1/2-wt patients. DOI: 10.1200/JCO.2020.38.15_suppl.3002 Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020) 3002-3002.

  RESULT

• Rocconi RP, Stevens EE, Bottsford-Miller JN, Ghamande SA, Elder J, DeMars LL, Munkarah A, Aaron P, Stanbery L, Wallraven G, Bognar E, Manley M, Horvath S, Manning L, Walter A, Galanis E, Herzog T, Monk BJ, Coleman RL, Nemunaitis J. Proof of principle study of sequential combination atezolizumab and Vigil in relapsed ovarian cancer. Cancer Gene Ther. 2022 Mar;29(3-4):369-382. doi: 10.1038/s41417-021-00317-5. Epub 2021 Mar 22.

  PMID: 33753870 RESULT

MeSH Terms

Conditions

Ovarian Neoplasms; Uterine Cervical Neoplasms; Uterine Neoplasms

Interventions

FANG vaccine; atezolizumab

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; Uterine Cervical Diseases; Uterine Diseases

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: No

Study Design

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

Model Details: This was a 3 part study. Parts 1 and 3 did not involve randomization. In part 2, eligible participants were randomized to receive two cycles of either Vigil alone or Atezolizumab alone, then followed by combination treatment with the two agents.

Study Record Dates

• First Submitted: February 23, 2017
• First Posted: March 8, 2017
• Study Start: May 31, 2017
• Primary Completion: May 22, 2019
• Study Completion: May 18, 2022
• Last Updated: April 5, 2023
• Results First Posted: April 5, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)