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.
The clinical trial was intended as a companion study to protocol CL-PTL-119 (VITAL study; NCT 02346747). Subjects who had tumor harvested at surgery and Vigil successfully manufactured, but then were ineligible for randomization onto the VITAL study or previously randomized to placebo, and also in subjects who have recurrent ovarian cancer were offered the opportunity to participate in this protocol. The trial was a multi-center, randomized, 3-part, open label study of Vigil, the checkpoint inhibitor atezolizumab and the combination of the two agents, in subjects with treatment refractory or recurrent epithelial ovarian cancer, or other gynecological cancers (i.e., cervical, uterine). Part 1 was a safety run-in cohort and intervention (Vigil plus atezolizumab) was combined. The first 3 subjects registered in the trial were assigned to Part 1. Part 2 was conducted after Part 1 participants completed combination therapy without dose-limiting toxicity. The purpose of Part 2 was to determine if Vigil given first then in sequence with atezolizumab would enhance immunotherapeutic anticancer activity. The overall efficacy of administration sequence was assessed. Eligible subjects were randomized to receive two cycles of Vigil alone (n= 11) or two cycles of atezolizumab alone (n=10), followed by combination treatment with both of the agents. Part 3 was an expansion cohort to allow subjects who completed all cycles of Part 2 to continue on atezolizumab alone, after Cycle 12. In this study, only 1 subject from Part 2 received additional treatment with atezolizumab. Pre-approval by sponsor was required by the sponsor before allowing subjects to continue treatment with atezolizumab in Part 3. Subjects remained on treatment until disease progression or death or product toxic effect. Disease progression was determined radiographically by local investigators using the Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). Part 1, radiological assessment of tumor response was performed at baseline and every third cycle thereafter. Tumor biopsy for correlative studies including scoring of tumor infiltrating lymphocyte (TIL) and PD-1 / PD-L1 expression analysis was obtained at tissue procurement and at any time after the end of cycle 3. Whole blood for correlative studies (immune function) was obtained at baseline, prior to study agent administration at the start of cycle 3 and every third cycle thereafter. Part 2, radiological assessment of tumor response was performed at baseline, at the end of cycle 2 of single agent therapy, and every third cycle thereafter. Tumor biopsy for correlative studies including scoring of tumor infiltrating lymphocyte (TIL) and PD-1 / PD-L1 expression analysis was obtained at tissue procurement, prior to the start of combination therapy and at any time after the end of cycle 3. Whole blood for correlative studies (immune function) was obtained at baseline, prior to study agent administration at the start of cycle 3 (the first cycle of combination therapy) and every third cycle thereafter. Part 3 schedule of assessments continued from Part 2 in which the following was assessed every third cycle: radiological assessments, tumor biopsy (if available), and whole blood collection for correlative studies. The safety evaluation included recording of AEs and SAEs, and changes from baseline in laboratory evaluations, vital signs, electrocardiograms, and physical examinations. Treatment was administered on an outpatient basis. A study cycle is defined as 21 days (3 weeks). Treatment was allowed to continue unless documented disease progression, discontinuation for toxicity, withdrawal of consent, or meeting other criteria for withdrawal from study. After progression, participants were contacted annually for three years for documentation of survival status information.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
25
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.
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.
University of South Alabama Mitchell Cancer Institute
Mobile, Alabama, United States
Georgia Cancer Center at Augusta University
Augusta, Georgia, United States
Henry Ford Hospital
Detroit, Michigan, United States
Billings Clinic
Billings, Montana, United States
Dartmouth-Hitchcock Medical Center/ Norris Cotton Cancer Center
Lebanon, New Hampshire, United States
Prisma Health Cancer Institute
Greenville, South Carolina, United States
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.
Time frame: AEs reported from first treatment dose and up to 30 days after last treatment, about 12 months.
Immune Response Rate
Whole blood for correlative studies will be obtained at baseline, at the start of cycle 3 (the first cycle of combination therapy), every 3 cycles thereafter and end of treatment.
Time frame: Up to 30 days after last treatment
Time to Progression
Overall assessment of time to progression and survival will be measured by Radiological Tumor Assessment by local investigators using the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. In Part 1, disease progression was assessed at baseline and every third cycle thereafter. In Part 2, the disease was assessed at baseline, at the end of Cycle 2 of single-agent therapy, and every third cycle thereafter.
Time frame: From baseline (prior to treatment) up to 3 years
Radiographic Overall Response Rate (ORR)
Radiographic ORR is defined as the percentage of participants achieving a Complete Response (CR) or Partial Response (PR), as assessed by investigators using RECIST 1.1. In Part 1, ORR was assessed at baseline and every third cycle thereafter. In Part 2, the disease was assessed at baseline, at the end of Cycle 2 of single-agent therapy, and every third cycle thereafter. 95% confidence interval from exact binomial distribution (Blopper-Pearson method).
Time frame: From first dose to end of study treatment (up to 9 months)
Overall Survival (OS)
OS is defined as time of randomization to date of death due to any cause.
Time frame: OS will be evaluated from time of randomization up to 37 months following documented disease progression.
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