RE:RE:RE:Immunogen IncAnti PD-1/PD-L1 single agent displayed a limited anti-tumor activity in un-selected patients with SCCA. Therefore, patients’ selection for immune checkpoint blockade still represents an unmet need. Selection is closely related to the urgency of more translational research to detect biomarkers that may predict who really benefit from PD-1/ PD-L1 blockade and identify driver mutations that may underlie immunogenicity.
Treatment options for squamous cell anal carcinoma following failure of first-line therapy are limited and include immune checkpoint inhibitors as outlined above. In recent studies, objective response rates to checkpoint inhibitor therapy of previously treated SCCA patients ranged from 10- 14%. Therapies that modify the tumor microenvironment may improve the susceptibility of tumors, including microsatellite stable (MSS) tumors, to immunotherapies. ONCY hypothesized that pela would make the tumor microenvironment more immunologically active, in part by increasing T cell infiltration and PD-L1 expression, thereby enhancing the effectiveness of checkpoint inhibitors in 2 nd-line or later SCCA. In support of this hypothesis, pelareorep-based combination therapies have demonstrated clinical activity in metastatic breast and pancreatic cancer. The Phase 1/2 GOBLET Cohort 4 findings involving pelareorep + PD-L1 atezolizumab +/- chemotherapy appears to support ONCYs hypothesis.
After decades of disappointing results, the therapeutic armamentarium of metastatic anal cancer is rapidly evolving. In this context, PD1/PD-L1 immune checkpoint is a relevant candidate target for immunotherapy in HPV + cancers, including SCCA. Despite the strong rationale, PD-1/PD-L1 blockade as a monotherapy induces only a limited number of long-term responses in SCCA. Therefore, combining anti-PD-1/PD-L1 drugs with other treatments, including chemotherapy, oncolytic virus (OV) therapy, vaccines, adoptive T cells or other ICIs is deemed to represent a promising strategy, as ONCYs Phase 1/2 GOBLET Cohort 4 clinical trial has demonstrated