dm+d

Unassigned

New Medicines

Vigil Ewing sarcoma

Information

Vigil
New molecular entity
Gradalis
Gradalis

Development and Regulatory status

None
None
Phase III Clinical Trials

Category

Personalised vaccine comprising autologous tumour cells that are loaded ex vivo with a Vigil™ expression vector plasmid encoding recombinant GM-CSF and furin bifunctional shRNA (bi-shRNA), which elicit a systemic T-cell directed immune response
Ewing sarcoma is the second most commonly diagnosed form of primary bone cancer in children & young adults. There are fewer than 100 cases of Ewing sarcoma diagnosed in the UK and Ireland each year. In the general population in Europe each year, there are slightly less than two cases of Ewing sarcoma diagnosed per million people (1.90 pe1,000,000). The peak of incidence (between 10 and 20 years of age) of Ewing sarcoma patients corresponds with times at which bones are growing fastest [1].
Ewing sarcoma
Intradermal

Trial or other data

Jul 20PIIb study (NCT02511132) is no longer recruiting and due to complete collection of primary outcome data (adverse effects) in Dec 20 [2].
Mar 20PIII VITA study is no longer recruiting [2].
Aug 18PIII VITA study to evaluate the efficacy of Bi-shRNAfurin and GMCSF augmented autologous tumor cell immunotherapy in combination with irinotecan and temozolomide as a second-line regimen in patients with Ewing sarcoma starts (CL-PTL-130; NCT03495921). The randomised, open-label study intends to enrol 114 patients aged 2 years and older in the US. Participants undergoing a standard surgical procedure (e.g., tumor biopsy or palliative resection) may have tumor tissue harvested for manufacture of Vigil. Primary outcome is progression-free survival; collection of these data is due to complete Dec 21 [2].
May 17PIIb study in patients with Ewing sarcoma, who are refractory or intolerant to at least one prior line of chemotherapy, to determine the one-year survival rate on treatment with intradermal Vigil™, in comparison with gemcitabine/docetaxel starts (CL-PTL-121; NCT02511132). Part 2 of the study will evaluate the safety and efficacy of temozolomide/irinotecan in combination with Vigil™. Sequential IFNγ-ELISPOT (immune activation) assay will be used to detect activated cancer-targeting lymphocytes, before and following treatment. The open-label study will enrol 22 patients in the US [3].

Vigil Stage IIIb, IIIc or IV high-grade papillary serous/ clear cell / endometrioid ovarian, fallopian tube or primary peritoneal cancer after surgery and primary chemotherapy

Information

Vigil
Licence extension / variation
Gradalis
Gradalis

Development and Regulatory status

None
None
Phase II Clinical Trials

Category

Personalised vaccine comprising autologous tumour cells that are loaded ex vivo with a Vigil™ expression vector plasmid encoding recombinant GM-CSF and furin bifunctional shRNA (bi-shRNA), which elicit a systemic T-cell directed immune response.
Cancer Research UK statistics show that in the UK in 2015-2017, there were 7,400 new ovarian cancer cases. Incidence rates for ovarian cancer in the UK are highest in females aged 75 to 79. Almost 6 in 10 ovarian cancer cases are diagnosed at a late stage. [1]
Stage IIIb, IIIc or IV high-grade papillary serous/ clear cell / endometrioid ovarian, fallopian tube or primary peritoneal cancer after surgery and primary chemotherapy
Intradermal

Trial or other data

Mar 21No UK trial sites. [2]
Mar 21Published results from VITAL trial demonstrated significant clinical benefit with improvement in RFS and overall survival in a pre-planned subgroup analysis in stage III/IV newly diagnosed ovarian cancer patients with BRCA wild type. In the homologous recombination subgroup, Vigil-treated pts experienced improved RFS (n=25) vs. placebo (n=20) (HR=0.386; 90% CI 0.199–0.750; p=0.007). Similarly, improved overall survival benefit was observed for treatment gp vs placebo (HR=0.342; 90% CI 0.141–0.832; p=0.019). Vigil-treated pts did not experience any Grade 3/4 treatment-related toxicities. [3]
Mar 21PIIb VITAL trial involved procuring tissue from ≥18 years age pts with IIIb, IIIc or IV high-grade papillary serous/clear cell/endometrioid ovarian, fallopian tube or primary peritoneal cancer prior to chemotherapy for manufacture of Vigil. Subsequently, Vigil was given to patients who had surgery and completed primary chemotherapy (n=91) monthly for at least 4 to 12 administrations vs placebo (NCT02346747). Primary outcome is Recurrence Free Survival (RFS). Estimated primary completion date is Dec 2022. [2]