Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

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.

Vigil™

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.

Luisa Manning, MD

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.

This is an open label phase 2 study to evaluate the combination of Vigil™ autologous tumor cell immunotherapy and nivolumab PD-1 inhibitor therapy in patients with advanced or metastatic NSCLC that is progressive on or after one prior platinum-based systemic therapy (ALK or EGFR mutation-targeted therapy should have been received if appropriate mutation present).

Patients undergoing a standard surgical procedure (e.g., tumor biopsy, palliative resection, or thoracentesis of malignant pleural effusion) may elect to have tumor tissue procured for manufacture of Vigil™ vaccine. 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. Three to six weeks after tissue procurement has occurred eligibility will be reconfirmed by the study site. Subjects must begin the study regimen within 6 weeks of tissue procurement. Radiological assessment of tumor response will be performed at screening, Cycle 5 (Week 9) and approximately every 2 months thereafter until progressive disease unless the subject is lost to follow-up, withdraws consent for study related procedures, or initiates another cancer therapy. Tumor biopsy for correlative studies should be obtained at tissue procurement and at Cycle 5 (Week 9). Peripheral blood mononuclear cells (PBMC) for correlative studies should be obtained before tumor procurement, and prior to initiation of study therapy on Day 1 at Cycle 1 (Week 1), Cycle 5 (Week 9), Cycle 9 (Week 17) and EOT.

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

A Phase 2 Study of Vigil™ Augmented Autologous Tumor Cell Immunotherapy in Combination With Nivolumab PD-1 Inhibitor for Patients With Advanced Non-Small Cell Lung Cancer

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.

Safety endpoints include all adverse events (CTCAE 4.03), laboratory safety assessments, and physical examination findings.

The secondary efficacy endpoint of PFS is the time from randomization to progression according to RECIST version 1.1 or until death from any cause, whichever comes first.

Gradalis, Inc.

Digestive System Diseases

Skin and Connective Tissue Diseases

Rare Diseases

Liver Neoplasms

Sarcoma

Sarcoma, Ewing

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Osteosarcoma

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Soft Tissue Sarcoma

Ewing Sarcoma

Hematinics

Vaccines

Liver Extracts

Molgramostim

Sargramostim

Immunologic Factors

Patients will be treated once a month as long as sufficient material is available for up to 12 doses

Minal Barve, MD

Autologous Vigil™ vaccine expresses rhGMCSF and bi-shRNAfurin from the Vigil™ plasmid. The GMCSF protein is a potent stimulator of the immune system, recruiting immune effectors to the site of intradermal injection and promoting antigen presentation. The furin bifunctional shRNA blocks furin protein production at the post transcriptional and translational levels. This decrease in furin in turn decreases the conversion of the proforms TGFβ1 and TGFβ2 proteins. Also, reduced furin protein levels have a negative feedback inhibition on TGFβ1 and TGFβ2 gene expression, decreasing the levels of their mRNAs. The resulting decrease in TGFβ1 and TGFβ2 proteins reduces the local immunosuppression they cause and promotes tumor surface antigen and MHC protein display.

Preliminary studies with a variety of vaccines suggest target accessibility (potential immunogenicity) in a variety of solid tumors to immune directed approaches. In an effort to overcome limitations of immunostimulatory cancer vaccines, we have designed a novel autologous vaccine to address inability to fully identify cancer associated antigens, antigen recognition by the immune system (i.e. antigen to immunogen), effector potency, and cancer-induced resistance. We have completed clinical investigations using two different gene vaccine approaches to induce enhancement of tumor antigen recognition which have demonstrated therapeutic efficacy. Specifically, both the use of a GMCSF gene transduced vaccine (GVAX®) and a TGFβ2 antisense gene vaccine (Lucanix®), in separate trials, have demonstrated similar beneficial effects without any evidence of significant toxicity in advanced cancer patients. The GMCSF transgene directly stimulates increased expression of tumor antigen(s) and enhances dendritic cell migration to the vaccination site. TGFβ2 blockade following intracellular TGFβ2 antisense gene expression reduces production of immune inhibiting activity at the vaccine site. This appears to be one of the primary mechanisms of inhibition of immune responsiveness in glioblastoma and lung cancer. In a subsequent Phase I trial we combined both active principles in one autologous vaccine, TAG. TAG vaccine has an excellent safety profile in the first nineteen patients treated (enrollment open to any solid tumor) with one documented CR (melanoma). However, TGFβ1 is the dominant TGFβ family inhibitory effector in the majority of other solid tumors. We describe a unique method of inhibiting both TGFβ1 and TGFβ2 through RNA interference with Furin. We will harvest autologous cancer cells from patients with advanced refractory cancer. We have constructed a bi-shRNAfurin / GMCSF (Vigil™) expression vector plasmid and have successfully demonstrated preclinical activity of the vector function following transfection by electroporation and irradiation of ex vivo autologous tumor cells.

Trial of Bi-shRNA-furin and GMCSF Augmented Autologous Tumor Cell Vaccine for Advanced Cancer

Phase I Trial of Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Vaccine for Advanced Cancer

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

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

Neoplasms, Glandular and Epithelial

Ovarian Cancer

Ovarian Epithelial Cancer

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.

Participants received standard of care without maintenance therapy.

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.

John Nemunaitis, MD

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.

This was a Phase II open-label study of Vigil™ autologous tumor cell vaccine trial administered to women with Stage III/IV epithelial ovarian cancer. Tumor was harvested at the time of surgical debulking (standard of medical care). Participants who achieved clinical complete response (CR) following primary surgical debulking and front-line doublet chemotherapy were randomized 2:1 to either treatment with Vigil (Group A) or standard of care without maintenance therapy (Group B). After randomization, participants were stratified into cohorts by baseline CA-125 (greater than 10 to less than 20 units/mL versus less than or equal to 10 units/mL). For data analysis, participants could further be stratified by surgical stage (Stage IV or suboptimal debulking (\> 1cm residual), Stage III disease versus Stage III disease with optimal debulking (\< 1cm residual). Participants enrolled in Group A (Vigil) received 1.0 x 10e7 cells / intradermal injection of gene transfected autologous tumor cells, Vigil™, once a month for up to 12 doses as long as sufficient material was available or until trial endpoints were met. Enough harvested tissue to provide a minimum of 4 monthly injections was required for entry into the study. Participants enrolled in Group B (Standard of Care, SOC) were observed and assessed until trial endpoints were met. Protocol Amendment 8, June 19, 2014 removed randomization such that all patients screening for enrollment into the main portion of the trial (including those who previously had tumor tissue harvested) would be assigned to Group A (Vigil).

Both groups of participants were seen once a month in an outpatient setting. Hematologic function, liver enzymes, renal function and electrolytes were monitored monthly. Immune function analysis including ELISPOT analysis of cytotoxic T cell function to autologous tumor antigens were monitored at (≤ 24 hours before the third cycle chemotherapy (post debulking), baseline (screening); prior to Vigil injection at Months 2, 3, 6 and EOT. CA-125 was monitored at baseline, every month for the first year, every 3 months +/- 2 weeks for the second and third year.

Participants assigned to group A were allowed to continue treatment with Vigil until disease recurrence or exhaustion of the patient's vaccine supply. If ≥ Grade 2 toxicity by NCI Common Toxicity Criteria (excluding Grade 2 fever ≤ 24 hours and Grade 2 and 3 injection site reactions) developed related to study treatment, the vaccine dose was reduced by 50% and continued on a monthly basis.

Efficacy assessments included time to disease recurrence, immune surrogate markers, and quality of life questionnaire (FACT-O, Version 4). Safety assessments included physical examination, performance status, and vital signs. Adverse events were recorded using CTCAE version 3.

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).

A Trial of FANG™ Vaccine for Participants With Ovarian Cancer

Open-label Phase II Trial of Adjuvant bishRNAfurin and GMCSF Augmented Autologous Tumor Cell Vaccine (FANG™) for High Risk Stage III/IV Ovarian Cancer

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.

Gamma interferon (γ-IFN) secretion measured by ELISpot assay was used as a marker for T-cell and immune activation to cancer specific neoantigens. Any participant that had greater than or equal to 10 spots were considered positive.

Predictive potential for TIL and TAM was expected to be measured from tissue collected at baseline and at recurrence.

AEs were reported using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Participants received Vigil at 1 x 10e7 cells/injection via intradermal injection for a minimum of 4 doses and a maximum of 12 doses. Participants were treated monthly for up to 12 months as long as sufficient Vigil was available and the participant was clinically stable.

Group A (Vigil™)

Group B (Observational - Standard of Care)

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

CA-125 > 10 U/ML but ≤ 20 U/mL

CA-125 ≤ to 10 U/mL

CA-125 > 20 U/mL

One subject CA-125 value was greater than 20 U/mL, which was outside the inclusion criteria range 0 to 20 U/mL. An exception was granted to allow the subject to enroll as the subject's CA-125 value was below the institutional upper limit of normal which is 34 U/mL.

CA-125 Level

Clinical and Regulatory Operations

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). Subjects were treated monthly for up to 12 months as long as sufficient Vigil was available and the subject was clinically stable.

Subjects received standard of care without maintenance therapy.

Participants who achieved complete clinical response (cCR) at the time of study entry were included in the analysis. After randomization, two participants from Group A were deemed unevaluable as they did not achieve cCR.

Time to Recurrence (TTR)

Only participants that were deemed evaluable were included in the analysis. Any participants that were determined to not be in complete response (cCR) after study entry were excluded from analysis.

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

Biopsies were not collected at recurrence, therefore the outcome could not be analyzed. Data were not analyzed.

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

Grade 3 or higher

Grade 2

Grade 1

Participants were counted at most once per preferred term and at most once per system organ class.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Vigil™ + Nivolumab in Advanced Non-Small Cell Lung Cancer	NCT02639234	Advanced Non-sm... Metastatic Non-... Lung Neoplasms	Vigil™ Nivolumab	18 Years -	Gradalis, Inc.
Trial of Bi-shRNA-furin and GMCSF Augmented Autologous Tumor Cell Vaccine for Advanced Cancer	NCT01061840	Ewings Sarcoma Non Small Cell ... Liver Cancer	Vigil™ Vigil™ Vigil™	12 Years -	Gradalis, Inc.
Trial of Bi-shRNA-furin and GMCSF Augmented Autologous Tumor Cell Vaccine for Advanced Cancer	NCT01061840	Ewings Sarcoma Non Small Cell ... Liver Cancer	Vigil™ Vigil™ Vigil™	12 Years -	Gradalis, Inc.
A Trial of FANG™ Vaccine for Participants With Ovarian Cancer	NCT01309230	Ovarian Cancer	Vigil™	18 Years -	Gradalis, Inc.
Trial of Bi-shRNA-furin and GMCSF Augmented Autologous Tumor Cell Vaccine for Advanced Cancer	NCT01061840	Ewings Sarcoma Non Small Cell ... Liver Cancer	Vigil™ Vigil™ Vigil™	12 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.