(P 439) AN OPEN LABEL MULTICENTER PHASE 2 STUDY WITH SAFETY LEAD IN OF INTRATUMORAL VUSOLIMOGENE ODERPAREPVEC IN COMBINATION WITH PEMBROLIZUMAB IN PATIENTS WITH ANGIOSARCOMA

Objective: Angiosarcoma is an aggressive soft tissue sarcoma of endothelial differentiation with a median overall survival of less than one year for metastatic disease. Standard treatments including paclitaxel or anthracycline based chemotherapies are associated with significant toxicities and tyrosine kinase inhibitors when used as single agents have limited response rates. Immune checkpoint inhibitors, either as monotherapy or in combination have demonstrated durable responses. Oncolytic virus (OV) immunotherapy when injected intratumorally can selectively replicate within cancer cells and lead to cell lysis thereby leading to an immune response. This ultimately leads to the elimination of the injected and non-injected distant tumors. Initial studies using OV and anti-PD1 combination have shown promising responses in immunotherapy naïve angiosarcoma patients. However, studies in patients progressing on anti-PD1 immunotherapy are lacking and are an unmet need.
Vusolimogene Oderparepvec (VO) is a selective replication competent herpes simplex virus herpes engineered and genetically armed with a fusogenic protein (GALV-GP R-) and hGM-CSF. In Phase 1/2 IGNYTE study trial cohort with anti-PD(L)-1 failed non melanomatous skin cancer including angiosarcoma patients, treated with intratumoral VO and IV nivolumab demonstrated an overall response rate of 33.3%.

Methods: Patients aged ≥18 years with biopsy-proven cutaneous angiosarcoma that is either locally advanced and unresectable or metastatic, who have received and progressed on a first-line taxane- or anthracycline-based regimen and have received at least one prior immunotherapy-based regimen within 6 months prior to screening, are eligible for enrollment. Patients must have adequate organ function and at least two measurable lesions per RECIST 1.1 criteria. All patients must provide informed consent prior to participation. Patients will receive a first intratumoral injection of VO, followed 14 days later by 7 additional VO injections every 3 weeks, administered concurrently with intravenous pembrolizumab. Disease assessments will be conducted at baseline and every 8 weeks thereafter. This trial will begin with a safety lead-in of 6 patients, followed by a Phase 2 expansion cohort of up to 18 patients. The primary endpoint is overall response rate (ORR), with a follow-up period of 2 years. Tissue and blood samples will be collected for correlative studies aimed at identifying biomarkers of immune response. (NCT06898970).

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Conclusion: N/A