GOBLET platform study: Preliminary safety and tumor response results for the relapsed anal carcinoma cohort in patients treated with pelareorep and atezolizumab.

6 Background: Patients with relapsed unresectable squamous cell carcinoma of the anal canal (SCCA) have limited treatment options after failure of standard first-line therapy. While checkpoint inhibitor monotherapy is possible, response rates are low (10-24%). Therapies that induce an inflammatory tumor microenvironment may improve the susceptibility of SCCA to immunotherapy. Pelareorep (pela) is a non-genetically modified, intravenously administered reovirus that stimulates the expansion of tumor-infiltrating lymphocyte (TIL) clones and simultaneously makes tumors visible to the immune system by upregulating interferon-induced gene expression. Pela-based combination therapies have demonstrated activity in metastatic breast and pancreatic cancer. In the GOBLET platform study, the efficacy of pela plus atezolizumab (atezo) in SCCA is being evaluated. Methods: GOBLET is a phase 1/2, open-label, non-randomized, Simon two-stage platform study in patients with advanced or metastatic GI cancers. SCCA patients in the trial are treated with pela plus atezo. Ten evaluable patients will be enrolled in Stage 1 and an additional 18 evaluable patients will be enrolled in Stage 2 if the prespecified Stage 1 success criterion is met (≥2 responses). The coprimary endpoints are tolerability of the treatment regimen and objective response rate (based on RECIST v1.1). Safety data are reviewed in an ongoing manner by an independent Data Safety Monitoring Board (DSMB). In addition, tumor and blood samples are being collected to assess TIL clonal expansion and other biomarkers. Results: Twelve patients are currently evaluable for tumor response in the SCCA cohort. Four out of 12 patients have achieved an objective response to therapy including 1 prolonged complete response (>15 months) and 3 partial responses- resulting in an ORR of 33.3%. Final ORR, progression-free survival, and overall survival results are pending. The DSMB has identified no safety signals and has recommended that enrollment continues without modification. TIL clonal expansion in the blood has been observed at treatment cycle 4 in all 3 responding patients for whom data are available. Conclusions: Twelve patients are currently evaluable for tumor response in the SCCA cohort. Four out of 12 patients have achieved an objective response to therapy including 1 prolonged complete response (>15 months) and 3 partial responses resulting in an ORR of 33.3%. Final ORR, progression-free survival, and overall survival results are pending. The DSMB has identified no safety signals and has recommended that enrollment continues without modification. TIL clonal expansion in the blood has been observed at treatment cycle 4 in all 3 responding patients for whom data are available. Clinical trial information: 2020-003996-16.