NCT02511132

A Two-part Phase IIb Trial of Vigil (Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Immunotherapy) in Ewing's Sarcoma

Completed Phase 2 Results posted Last updated 22 December 2022

What this trial tests

Phase 2 trial testing Vigil in Ewing's Sarcoma in 22 participants. Completed in 23 December 2020.

Timeline

10 February 2016

Primary endpoint
12 November 2018

23 December 2020

Quick facts

Lead sponsor	Gradalis, Inc.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	22
Start date	10 February 2016
Primary completion	12 November 2018
Estimated completion	23 December 2020
Sites	6 locations across United States

Drugs / interventions tested

• Vigil — full drug profile →
• Temozolomide (temozolomide) — full drug profile →
• Irinotecan (irinotecan) — full drug profile →
• Gemcitabine (gemcitabine) — full drug profile →
• Docetaxel (Docetaxel) — full drug profile →

Conditions studied

• Ewing's Sarcoma — all drugs for Ewing's Sarcoma →

Sponsor

Gradalis, Inc. — full company profile →

Who can join

2 and older, any sex, with Ewing's Sarcoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Adverse Events Determined by Laboratory Assessments and Physical Examinations Primary · 30 days of last treatment dosing

To determine safety profile of Vigil immunotherapy in combination with irinotecan and temozolomide with 30 days of last dose in patients with metastatic Ewing's sarcoma refractory or intolerant to at least 1 prior line of systemic chemotherapy. • To determine safety profile of Vigil immunotherapy in combination with irinotecan and temozolimidetemozolomide in patients with metastatic Ewing's sarcoma refractory or intolerant to at least 1 prior line of systemic chemotherapy.

Group	Value	95% CI
Part 1: Vigil Alone	5
Part 1: Gemcitabine and Docetaxel	6
Part 2: Vigil in Combination With Temozolomide and Irinotecan	9

Progression Free Survival Secondary · Estimated median 1.3 years

Progression Free Survival (PFS) is defined as the time from randomization to the event of disease recurrence/progression defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) or death due to any cause. To determine the progression free survival of subjects dosed with Vigil immunotherapy in combination with irinotecan and temozolomide.

Group	Value	95% CI
Part 1: Vigil Alone	5
Part 1: Gemicitabine and Docetaxel	6
Part 2: Vigil in Combination With Temozolomide and Irinotecan	9

Overall Survival Secondary · Estimated median 2 years

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.

Group	Value	95% CI
Part 1: Vigil Alone	3
Part 1: Gemcitabine and Docetaxel	6
Part 2: Vigil in Combination With Temozolomide and Irinotecan	5

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were recorded for the duration of a patient's study treatment: from the first dose of the Investigational Product to 30 days following the last study treatment (up to 10 months).. Reporting threshold: 3%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Part 1: Vigil Alone

Serious: 2/5 (40%)

Deaths: 4/4

Part 1: Gemicitabine and Docetaxel

Serious: 5/8 (63%)

Deaths: 8/8

Part 2: Vigil Plus Temozolomide and Irinotecan

Serious: 5/9 (56%)

Deaths: 9/9

Serious adverse events (22 terms)

Reaction	System	Part 1: Vigil Alone	Part 1: Gemicitabine and D…	Part 2: Vigil Plus Temozol…
Vomiting	Gastrointestinal disorders	—	—	—
Edema extremities	General disorders	—	—	—
Disease progression	General disorders	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Dyspnea	Respiratory, thoracic and mediastinal disorders	—	—	—
Brain mass	Nervous system disorders	—	—	—
Blisters	Skin and subcutaneous tissue disorders	—	—	—
Facial swelling	Skin and subcutaneous tissue disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Hypertension	Vascular disorders	—	—	—
Febrile neutropenia	Blood and lymphatic system disorders	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Fever	General disorders	—	—	—
Pain	General disorders	—	—	—
Empyema	Infections and infestations	—	—	—
Pneumonia	Infections and infestations	—	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—
Platelets decreased	Investigations	—	—	—
WBC decreased	Investigations	—	—	—
Anaphylaxis	Immune system disorders	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—

Other adverse events (110 terms — click to expand)

Reaction	System	Part 1: Vigil Alone	Part 1: Gemicitabine and D…	Part 2: Vigil Plus Temozol…
Anemia	Blood and lymphatic system disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—
Fatigue	General disorders	—	—	—
Neutropenia	Blood and lymphatic system disorders	—	—	—
Anorexia	Metabolism and nutrition disorders	—	—	—
Thrombocytopenia	Blood and lymphatic system disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Fever	General disorders	—	—	—
Hypokalemia	Metabolism and nutrition disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Tachycardia	Cardiac disorders	—	—	—
Eye disorder	Eye disorders	—	—	—
Blurred vision	Eye disorders	—	—	—
Edema extremities	General disorders	—	—	—
Chest pain	General disorders	—	—	—
Alkaline phosphatase increased	Investigations	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—
Chest wall pain	Musculoskeletal and connective tissue disorders	—	—	—
Jaw pain	Musculoskeletal and connective tissue disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Neuropathy	Nervous system disorders	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
Itching	Skin and subcutaneous tissue disorders	—	—	—
Rash	Skin and subcutaneous tissue disorders	—	—	—
Iron deficiency anemia	Blood and lymphatic system disorders	—	—	—
Bradycardia	Cardiac disorders	—	—	—
Sinus tachycardia	Cardiac disorders	—	—	—
Chronic heart failure	Cardiac disorders	—	—	—
Pericardial effusion	Cardiac disorders	—	—	—
External ear inflammation	Ear and labyrinth disorders	—	—	—
Hearing loss	Ear and labyrinth disorders	—	—	—
Hypothyroidism	Endocrine disorders	—	—	—
Dry eyes	Eye disorders	—	—	—
Photophobia	Eye disorders	—	—	—
Watering eyes	Eye disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Dysphagia	Gastrointestinal disorders	—	—	—
Emesis	Gastrointestinal disorders	—	—	—

Most-reported serious reactions: Vomiting, Edema extremities, Disease progression, Back pain, Dyspnea, Brain mass, Blisters, Facial swelling.

Data from ClinicalTrials.gov NCT02511132 adverse events section.

Sponsor's own description

A two-part trial in patients with metastic Ewing's sarcoma. Participants in Part 1 will be randomized to receive either Vigil immunotherapy or gemcitabine and docetaxel with the objective of comparing the overall survival between the two arms. Participants enrolled in Part 2 will receive Vigil immunotherapy in combination of temozolomide and irinotecan with the objective to determine the safety profile of the combination treatment.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Novel therapies emerging in oncology to target the TGF-β pathway.
   Kim BG, Malek E, Choi SH, Ignatz-Hoover JJ, et al · · 2021 · cited 336× · PMID 33823905 · DOI 10.1186/s13045-021-01053-x
2. TGF-β signaling in the tumor metabolic microenvironment and targeted therapies.
   Shi X, Yang J, Deng S, Xu H, et al · · 2022 · cited 188× · PMID 36115986 · DOI 10.1186/s13045-022-01349-6
3. Novel TGF-<b>β</b> inhibitors ready for prime time in onco-immunology.
   de Gramont A, Faivre S, Raymond E. · · 2017 · cited 148× · PMID 28197376 · DOI 10.1080/2162402x.2016.1257453
4. Biology of Bone Sarcomas and New Therapeutic Developments.
   Brown HK, Schiavone K, Gouin F, Heymann MF, et al · · 2018 · cited 116× · PMID 29238848 · DOI 10.1007/s00223-017-0372-2
5. Three-year Follow up of GMCSF/bi-shRNA(furin) DNA-transfected Autologous Tumor Immunotherapy (Vigil) in Metastatic Advanced Ewing's Sarcoma.
   Ghisoli M, Barve M, Mennel R, Lenarsky C, et al · · 2016 · cited 71× · PMID 27109631 · DOI 10.1038/mt.2016.86
6. Ewing Sarcoma Single-cell Transcriptome Analysis Reveals Functionally Impaired Antigen-presenting Cells.
   Visser LL, Bleijs M, Margaritis T, van de Wetering M, et al · · 2023 · cited 29× · PMID 37823774 · DOI 10.1158/2767-9764.crc-23-0027
7. Exploiting Signaling Pathways and Immune Targets Beyond the Standard of Care for Ewing Sarcoma.
   Casey DL, Lin TY, Cheung NV. · · 2019 · cited 26× · PMID 31275859 · DOI 10.3389/fonc.2019.00537
8. Targeting transforming growth factor beta signaling in metastatic osteosarcoma.
   Ge R, Huang GM. · · 2023 · cited 25× · PMID 38021074 · DOI 10.1016/j.jbo.2023.100513