Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Breast Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Uterine Cervical Neoplasms

Uterine Neoplasms

Endometrial Neoplasms

Fallopian Tube Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Uterine Cervical Diseases

Uterine Diseases

Fallopian Tube Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Immunomodulating Agents

Durvalumab

Immunoglobulins

Immunoglobulin G

Immunoglobulins, Intravenous

Antineoplastic Agents, Immunological

The first part will be a safety run-in comprised of 2 cohorts that will use a 3 + 3 design to determine the Vigil dose in Part 2. Cohort 1 will receive a low dose of Vigil (1x10\^6 cells/intradermal (ID) injection) in combination with durvalumab (1500 mg (if \> 30 kg) IV over 60 minutes) every 4 weeks.

Cohort 2 will receive Vigil at 1x10\^7 cells/ID injection and durvalumab (1500mg (if \> 30 kg) IV over 60 minutes) every 4 weeks.

If needed, Cohort -1 will be used which will receive Vigil at 1x10\^5 cells/ID injection and Durvalumab (1500mg (if \> 30 kg) IV over 60 minutes) every 4 weeks.

Vigil 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.

Vigil

A human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody directed against programmed cell death ligand 1 (PD-L1)

Minal Barve, MD

In this study, the researchers want to learn more about Vigil and durvalumab in advanced women's cancers: 1) how much of Vigil in combination with durvalumab (MEDI4736) can be given with an acceptable level of side effects, 2) the effects of Vigil and durvalumab in combination (good and bad), 3) if Vigil will cause changes in cancer cells that may help durvalumab attack the cancer, and 4) whether or not Vigil and durvalumab will slow your cancer or stop your cancer from getting worse.

Combining Vigil with durvalumab will allow the former to induce (or increase) the infiltration of activated T cells into tumors, and in addition, to enhance PD-L1 (programmed cell death ligand 1) expression. Consequently, the response rate of historically low or un-responsive cancer will be increased with the combination of Vigil and anti PD-L1.

This is an open label pilot study to evaluate the safety, tolerability, and efficacy of the combination of Vigil autologous tumor cell immunotherapy and durvalumab PD-L1 inhibitor in patients with locally advanced or metastatic women's cancers, inclusive, but not limited to breast, ovarian, cervical, uterine, fallopian, primary peritoneal, and endometrial regardless of the number of prior therapies.

This will be a 2-part study. The first part will be a safety run-in comprised of 2 cohorts that will use a 3 + 3 design to determine the Vigil dose in Part 2. Patients in Cohort 1 will receive a low dose of Vigil (1x10\^6 cells/intradermal (ID) injection) in combination with durvalumab (1500 mg (if \> 30 kg) IV over 60 minutes) every 4 weeks. Patients in Cohort 2 will receive Vigil at 1x10\^7 cells/ID injection and durvalumab (1500mg (if \> 30 kg) IV over 60 minutes) every 4 weeks. If needed, patients in Cohort -1 will receive Vigil at 1x10\^5 cells/ID injection and durvalumab (1500mg (if \> 30 kg) IV over 60 minutes) every 4 weeks. The enrollment of the first two patients in each Cohort of Part 1 will be staggered by 2 weeks. In Part 2 of the study, patients meeting study eligibility criteria will receive Vigil at the dose determined in Part 1 and durvalumab (1500mg (if \> 30 kg) IV over 60 minutes) every 4 weeks. As of March 13, 2018, Part 2 of the study will not be initiated due to limited enrollment. Currently only patients who have Vigil immunotherapy available from Gradalis protocol CL-PTL-119 may be considered for the study.

Radiological assessment of tumor response or alternative assessments of disease status should be performed at screening, Cycle 3 and every 2 cycle thereafter, and end of treatment (EOT) using RECIST 1.1 and investigator assessment as applicable. Tumor biopsy for correlative studies including but not limited to scoring of tumor infiltrating lymphocyte (TIL) and PD-1 / PD-L1 expression analysis should be obtained at tissue procurement and at Cycle 3, and optional biopsies thereafter if the patient has accessible tissue. Peripheral blood mononuclear cells (PBMC) for correlative studies should be obtained at pre-procurement if applicable, and prior to study regimen administration at Cycle 1, Cycle 3, Cycle 5 and EOT. Patient survival will be followed for 1 year after last dose of either Vigil or durvalumab.

Pilot Study of Durvalumab and Vigil in Advanced Women's Cancers

Pilot Study of Durvalumab (MEDI4736) in Combination With Vigil in Advanced Women's Cancers

The safety evaluation will include collection of AEs, SAEs and changes from baseline in laboratory evaluations, vital signs, ECGs and physical exams. AEs will be graded according to the NCI CTCAE v4.03.

The ORR will be estimated in patients with measurable disease, along with its exact binomial 95% confidence interval.

Disease status will be summarized based on tumor markers or ascites/pleural fluid in patients with non-measurable disease

Gradalis, Inc.

AstraZeneca

Mary Crowley Medical Research Center

Atezolizumab

Vaccines

Immune Checkpoint Inhibitors

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.

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

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

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

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.

John Nemunaitis, MD

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.

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.

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

A Randomized, Intra-patient Crossover, Safety, Biomarker and Anti-Tumor Activity Assessment of the Combination of Atezolizumab and Vigil in Patients With Advanced Gynecological Cancers (A Companion Study to CL-PTL-119)

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.

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.

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.

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).

OS is defined as time of randomization to date of death due to any cause.

Roche-Genentech

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. Vigil was administered first, followed 30 minutes later by atezolizumab. 1 cycle = 21 days.

Part 1: Vigil + Atezo

Part 2 participants randomized to Vigil first received Vigil immunotherapy at a concentration of 1 x 10e6 or 1 x 10e7 cells/dose given via intradermal injection for the first two cycles.

1 cycle = 21 days

Part 2: Vigil

Part 2 participants randomized to atezolizumab first received atezolizumab at a dose of 1200 mg as an intravenous infusion for the first two cycles. 1 cycle = 21 days

Part 2: Atezo

After Part 2 participants completed the first two cycles of Vigil or atezolizumab, then Vigil and atezolizumab was given in sequence.

Vigil immunotherapy was administered at a concentration of 1 x 10e6 or 1 x 10e7 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. Vigil was administered first, followed 30 minutes later by atezolizumab. 1 cycle = 21 days

Part 2: Vigil and Atezo

Participants continue on single agent atezolizumab until disease progression. Atezolizumab was administered at a dose of 1200 mg as an intravenous infusion. 1 cycle = 21 days.

Part 3: Atezo

After Part 1 participants 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 immunotherapy was administered at a concentration of 1 x 10e6 or 1 x 10e7 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 was administered first, followed 30 minutes later by atezolizumab.

1 cycle = 21 days

Part 2: Vigil Then Vigil + Atezo

After Part 1 participants 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 immunotherapy was administered at a concentration of 1 x 10e6 or 1 x 10e7 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 was administered first, followed 30 minutes later by atezolizumab. 1 cycle = 21 days

Part 2: Atezo Then Vigil + Atezo

Total

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

The number of prior lines of systemic therapies was obtained from medical records during the pre-study period. Systemic therapies refers to any type of cancer treatment that targets the entire body.

Number of Prior Lines of Systemic Therapies

Eastern Cooperative Oncology Group (ECOG) Performance Status Scale is a standard way of to assess how a patient with cancer is progressing, assess how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis. ECOG scores range from 0 to 5. A lower score means the patient is better able to carry out daily activities. The assessment is made during the clinical study visit.

Baseline ECOG

Number of subjects randomized with recurrent ovarian cancer or failed to meet eligibility criteria of CL-PTL-119. There was no separate analysis for Part 3 as the one subject's data was included in Part 2 analysis.

Clinical and Regulatory Operations

Grade 4 Atezolizumab-Related

Grade 4 Vigil-Related

Grade 3 Atezolizumab-Related

Grade 3 Vigil-Related

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. Vigil was administered first, followed 30 minutes later by atezolizumab.

1 cycle = 21 days.

Patients in Part 1 completed combination therapy without dose-limiting toxicity justifying expansion to Part 2. This arm was to determine if Vigil given first then combined with atezolizumab would enhance immunotherapeutic anticancer activity. Overall, efficacy of administration sequence was assessed.

Vigil immunotherapy was administered at a concentration of 1 x 10e6 or 1 x 10e7 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 was administered first, followed 30 minutes later by atezolizumab.

1 cycle = 21 days

Patients in Part 1 completed combination therapy without dose-limiting toxicity justifying expansion to Part 2. This arm was to determine if atezolizumab given first then combined with Vigil would enhance immunotherapeutic anticancer activity. Overall, efficacy of administration sequence was assessed.

Vigil immunotherapy was administered at a concentration of 1 x 10e6 or 1 x 10e7 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 was administered first, followed 30 minutes later by atezolizumab. 1 cycle = 21 days

Grade 3/4 treatment-related events from first dose up to 30 days after last treatment.

Number of Treatment-emergent AEs of Vigil + Atezolizumab

After Part 1 participants completed combination therapy without dose-limiting toxicity, Part 2 participants randomized to Vigil first received two cycles of Vigil alone, then Vigil and atezolizumab given in sequence.

Vigil immunotherapy was administered at a concentration of 1 x 10e6 or 1 x 10e7 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 was administered first, followed 30 minutes later by atezolizumab.

1 cycle = 21 days

After Part 1 participants completed combination therapy without dose-limiting toxicity, Part 2 participants randomized to atezolizumab first received two cycles of atezolizumab alone, then Vigil and atezolizumab given in sequence.

Vigil immunotherapy was administered at a concentration of 1 x 10e6 or 1 x 10e7 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 was administered first, followed 30 minutes later by atezolizumab. 1 cycle = 21 days

Samples were not analyzed for immune response data.

Immune Response Rate

Part 1 is a safety run-in cohort. Vigil immunotherapy will be administered 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 will be administered at a dose of 1200 mg as an intravenous infusion every 3 weeks. The initial dose is to be administered over one hour and if well tolerated, subsequent infusions may be administered over 30 minutes. Vigil should be administered first, followed 30 minutes later by atezolizumab.

Vigil: 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 (TGFβ-1 and TGFβ-2).

Atezolizumab: Atezolizumab is provided in a single-use, 20-cc USP/Ph. Eur. Type 1 glass vial as a colorless to slightly-yellow, sterile, preservative-free clear liquid solution intended for IV administration. The vial is designed to deliver 20 mL (1200 mg) of atezolizumab solution but may contain more than the stated volume to enable delivery of the entire 20 mL volume. The atezolizumab drug product is formulated as 60 mg/mL atezolizumab in 20 mM histidine acetate, 120 mM sucrose, 0.04% polysorbate 20, pH 5.8.

Part 2 is a randomized, open label study of Vigil, the checkpoint inhibitor Atezolizumab and the combination of the two agents.

Vigil immunotherapy will be administered 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 for 2 cycles (1 cycle = 21 days).

Vigil: 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 (TGFβ-1 and TGFβ-2).

Atezolizumab: Atezolizumab is provided in a single-use, 20-cc USP/Ph. Eur. Type 1 glass vial as a colorless to slightly-yellow, sterile, preservative-free clear liquid solution intended for IV administration. The vial is designed to deliver 20 mL (1200 mg) of atezolizumab solution but may contain more than the stated volume to enable delivery of the entire 20 mL volume. The atezolizumab drug product is formulated as 60 mg/mL atezolizumab in 20 mM histidine acetate, 120 mM sucrose, 0.04% polysorbate 20, pH 5.8 (Phase III formulation).

Part 2 is a randomized, open label study of Vigil, the checkpoint inhibitor Atezolizumab and the combination of the two agents

Atezolizumab will be administered at a dose of 1200 mg as an intravenous infusion every 3 weeks for 2 cycles (1 cycle = 21 days). The initial dose is to be administered over one hour and if well tolerated, subsequent infusions may be administered over 30 minutes.

Vigil: 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 (TGFβ-1 and TGFβ-2).

Atezolizumab: Atezolizumab is provided in a single-use, 20-cc USP/Ph. Eur. Type 1 glass vial as a colorless to slightly-yellow, sterile, preservative-free clear liquid solution intended for IV administration. The vial is designed to deliver 20 mL (1200 mg) of atezolizumab solution but may contain more than the stated volume to enable delivery of the entire 20 mL volume. The atezolizumab drug product is formulated as 60 mg/mL atezolizumab in 20 mM histidine acetate, 120 mM sucrose, 0.04% polysorbate 20, pH 5.8 (Phase III formulation).

Time to Progression

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. Vigil was administered first, followed 30 minutes later by atezolizumab. 1 cycle = 21 days

Radiographic Overall Response Rate (ORR)

Overall Survival (OS)

After Part 1 participants 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 immunotherapy was administered at a concentration of 1 x 10e6 or 1 x 10e7 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 was administered first, followed 30 minutes later by atezolizumab.

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

After Part 1 participants 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 immunotherapy was administered at a concentration of 1 x 10e6 or 1 x 10e7 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 was administered first, followed 30 minutes later by atezolizumab.

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

Overall Study

Symptoms and General Pathology

Musculoskeletal Diseases

Sarcoma

Recurrence

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Neoplasms by Histologic Type

Neoplasms, Connective and Soft Tissue

Neoplasms, Connective Tissue

Neoplasms, Bone Tissue

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Bone Neoplasms

Osteosarcoma

Disease Attributes

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Connective Tissue Diseases

Bone Diseases

Soft Tissue Sarcoma

Ewing Sarcoma

Neuroepithelioma

Irinotecan

Temozolomide

Camptothecin

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Participants randomized to Group A received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). Vigil immunotherapy was administered at a concentration of 1 X 10e6 cells/dose given via intradermal injection on Day 15 of each cycle. 1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.

Participants randomized to Group B received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle).

1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.

Participants randomized to Group B were able to receive Vigil immunotherapy at a concentration of 1 X 10e6 cells/dose given via intradermal injection on Day 15 of each cycle. Confirmation of progression by central radiologist and pre-approval from sponsor was required. 1 cycle = 21 days

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.

Injectable formulation of irinotecan was distributed from central supplier. 1 Cycle (5 doses of 50 mg/m2 per syringe) was drawn into provided oral syringes and dispenses to the subject with instructions to refrigerate until administration.

Dose: 100 mg/m2 daily, oral Schedule: Days 1-5, every 21 days Administered at least 1 hour before Irinotecan.

The goal of this clinical trial was to compare participants with first relapse or refractory Ewing's sarcoma when treated with investigational product (Vigil) in addition to the standard treatment of irinotecan and temozolomide compared to the standard treatment of irinotecan and temozolomide alone. The main question it aimed to answer is "Will participants who receive Vigil in addition to irinotecan and temozolomide have a prolonged time to progression and improved quality of life compared to the participants who receive irinotecan and temozolomide alone?".

This was a multicenter, Phase III study in participants with metastatic Ewing's sarcoma Family of Tumors (ESFT) refractory/intolerant or recurrent to 1 prior line of chemotherapy. Participants who agreed to participation had tumor tissue harvested from a scheduled standard surgical procedure (e.g., tumor biopsy or palliative resection). The tumor tissue removed was shipped to Gradalis, Inc. to attempt to manufacture the investigational product, Vigil.

Subjects who met eligibility criteria including manufacture of a minimum of 4 doses of Vigil were randomized 1:1 to either Group A (Vigil + Irinotecan + Temozolomide (Tem/Iri)) or Group B (Irinotecan + Temozolomide). Screening for the main portion of the study occurred as early as one week but no later than 8 weeks following tumor procurement.

Subjects received repeat cycles of treatment until disease progression, unacceptable toxicity, withdrawal of consent or other criterion was met for discontinuation from study. Subjects randomized to Group A (Vigil + Tem/Iri) received up to 12 doses depending upon the quantity of Vigil manufactured from the surgical specimen. 1 cycle = 21 days. If irinotecan + temozolomide was administered beyond 12 cycles, it was administered off study. Subjects randomized to Group B (Tem/Iri) may have crossed over to receive single agent Vigil every 21 days following End of Treatment assessment and documented disease progression confirmed by central radiology vendor, for up to 12 doses of Vigil depending upon the quantity of Vigil manufactured.

Participants were managed in an outpatient setting. Hematologic function, liver enzymes, renal function and electrolytes will be monitored. Blood for immune function analyses including IFNγ-ELISPOT analysis of cytotoxic T cell activation in response to autologous tumor antigens will be collected at tissue procurement, post-procurement screening and Day 1 (prior to chemotherapy administration) at Cycles 2, 4, and 6, end of treatment (EOT), 3 months after EOT, and every 6 months thereafter. Blood for ctDNA analysis was collected at tissue procurement, prior to chemotherapy administration at baseline and on Day 1 prior to chemotherapy administration at Cycles 2, 3, 4, and 6, and EOT. After progression, participants were contacted quarterly for documentation of post study therapies and survival status information.

Participants were randomized 1:1 to either Group A (Vigil + irinotecan and temozolomide) or Group B (irinotecan and temozolomide alone). Participants randomized to Group B were able to receive Vigil (Cross-Over) after confirmation of progression by central radiologist and sponsor approval.

A Trial For Participants With Ewing's Sarcoma Treated With Vigil in Combination With Irinotecan and Temozolomide

A Multi-Center Phase III, Randomized, Open-Label Trial of Vigil (Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Immunotherapy) in Combination With Irinotecan and Temozolomide as a Second-Line Regimen for Ewing's Sarcoma

Progression Free Survival (PFS) is defined as the time from randomization to the event of disease recurrence/progression according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) for target lesions and assessed CT/MRI by local investigator.

OS is defined as time from randomization to death or to the date of last follow-up. The date of last follow-up confirming survival will be used as the censoring date for subjects who are alive and/or do not have a known date of death.

ORR is defined as the proportion of participants who have prolonged stable disease or a partial or complete response or complete response to therapy according to RECIST 1.1.

Participants were considered eligible for treatment, if the tissue submitted to Gradalis met all criteria, including manufacturing product release criteria.

Participants randomized to Group A received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). Vigil immunotherapy was administered at a concentration of 1 X 10e6 cells/dose given via intradermal injection on Day 15 of each cycle. 1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion was met for discontinuation from study.

Group A: Vigil in Combination With Irinotecan and Temozolomide

Participants randomized to Group B received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle).

1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion was met for discontinuation from study.

Group B: Irinotecan and Temozolomide

Participants assigned to Group B crossed-over to received Vigil monotherapy at a concentration of 1 X 10e6 cells//dose via intradermal injection every 21 days following End of Treatment assessment.

Participants received up to 12 doses of Vigil depending upon the quantity of Vigil manufactured.

Cross-over to Vigil Alone

Participants randomized to Group A received oral temozolomide 100 mg/m\^2 daily (Days 1-5), total dose 500 mg/m\^2/cycle) and oral irinotecan 50 mg/m\^2 daily (Days 1-5, total dose 250 mg/m\^2/cycle). Vigil immunotherapy was administered at a concentration of 1 X 10e6 cells/dose given via intradermal injection on Day 15 of each cycle. 1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.

Participants randomized to Group B received oral temozolomide 100 mg/m\^2 daily (Days 1-5), total dose 500 mg/m\^2/cycle) and oral irinotecan 50 mg/m\^2 daily (Days 1-5, total dose 250 mg/m\^2/cycle).

1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.

Ethnicity (NIH/OMB)

An assessment of Performance Status (PS) on the Karnofsky or Lansky scale is standard way of measuring the ability of cancer patients to perform ordinary tasks. The PS scores range from 0 to 100. A higher score means the patient is better able to carry out daily activities. The assessment is made by an investigator during the physical exam of the subject.

Baseline Performance Status

Only 1 subject randomized to Group B was eligible to Cross-over to receive Vigil.

Early termination of trial leading to small numbers of subjects analyzed. Technical problems with measurement leading to unreliable or uninterpretable data.

Participants randomized to Group B received oral temozolomide 100 mg/m2 daily (Days 1-5), total dose 500 mg/m2/cycle) and oral irinotecan 50 mg/m2 daily (Days 1-5, total dose 250 mg/m2/cycle). 1 cycle = 21 days

Participants continued treatment for a maximum of 12 cycles, or until disease progression, unacceptable toxicity, withdrawal of consent or other criterion is met for discontinuation from study.

PFS is not adequately assessable for difference between cohorts given only 5 participants were enrolled and received treatment.

Progression Free Survival (PFS)

OS is not adequately assessable for difference between cohorts given only 5 participants were enrolled and received treatment.

No subjects on trial achieved a partial or complete response, therefore the ORR was not determined.

Overall Response Rate (ORR)

Participants who underwent tissue procurement and the processed tissue samples were successfully shipped to Gradalis whereby Vigil production was attempted.

Total Number of Tissue Procurements

All enrolled subjects who completed tissue procurement and the tissue was received by Gradalis for Vigil Manufacture. Any subjects whose tissue was not submitted to Gradalis was excluded in the analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Pilot Study of Durvalumab and Vigil in Advanced Women's Cancers	NCT02725489	Breast Cancer Ovarian Cancer Fallopian Tube ... Primary Periton... Uterine Cancer Cervical Cancer Endometrial Can...	Vigil Durvalumab	18 Years -	Mary Crowley Medical Research Center
A Trial of Atezolizumab and Vigil in Patients With Advanced Gynecological Cancers	NCT03073525	Advanced Gyneco... Ovarian Cancer Cervical Cancer Uterine Cancer	Vigil Atezolizumab	18 Years -	Gradalis, Inc.
A Trial For Participants With Ewing's Sarcoma Treated With Vigil in Combination With Irinotecan and Temozolomide	NCT03495921	Ewing Sarcoma Ewing Family of... Ewing's Tumor M... Ewing's Sarcoma... Ewing's Tumor R... Rare Diseases Sarcoma Neoplasms, Conn... Neoplasms by Hi... Neoplasms, Bone... Neoplasms, Conn... Sarcoma, Ewing Neoplasms	Vigil Irinotecan Temozolomide	2 Years -	Gradalis, Inc.
A Two-part Phase IIb Trial of Vigil (Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Immunotherapy) in Ewing's Sarcoma	NCT02511132	Ewing's Sarcoma	Vigil Temozolomide Irinotecan Gemcitabine Docetaxel	2 Years -	Gradalis, Inc.
A Trial of Atezolizumab and Vigil in Patients With Advanced Gynecological Cancers	NCT03073525	Advanced Gyneco... Ovarian Cancer Cervical Cancer Uterine Cancer	Vigil Atezolizumab	18 Years -	Gradalis, Inc.
Phase II FANG™ in Advanced Melanoma	NCT01453361	Advanced Melano...	Vigil™ Vaccine	18 Years -	Gradalis, Inc.
Pilot Study of Durvalumab and Vigil in Advanced Women's Cancers	NCT02725489	Breast Cancer Ovarian Cancer Fallopian Tube ... Primary Periton... Uterine Cancer Cervical Cancer Endometrial Can...	Vigil Durvalumab	18 Years -	Mary Crowley Medical Research Center
Expanded Access of Vigil in Solid Tumors	NCT03842865	Solid Tumor Ewing Sarcoma Ewing's Tumor M... Ewing's Sarcoma... Advanced Gyneco... Ovarian Cancer Cervical Cancer Uterine Cancer	Vigil	2 Years -	Gradalis, Inc.
A Trial of Vigil for Participants With Ovarian Cancer	NCT02346747	Ovarian Cancer Ovarian Neoplas...	Vigil Placebo	18 Years -	Gradalis, Inc.
A Trial of FANG™ Vaccine for Participants With Ovarian Cancer	NCT01309230	Ovarian Cancer	Vigil™	18 Years -	Gradalis, Inc.

Spots Global Cancer Trial Database for vigil

Every month we try and update this database with for vigil cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for vigil

Every month we try and update this database with for vigil cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for vigil cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.