Pelareorep Combo Yields Responses in Squamous Cell Anal Carcinoma

Combining the investigational oncolytic virus pelareorep with atezolizumab (Tecentriq) demonstrated responses in a small cohort of patients with squamous cell anal carcinoma (SCAC), according to a press release on findings from the phase 1/2 GOBLET trial (2020-003996-16).¹

Among evaluable patients, the combination yielded an objective response rate (ORR) of 30% (n = 6/20) when used in the second line of therapy or later. According to the developers, this ORR exceeded a historical benchmark of 13.8% reported for the only commercially available second-line therapy for SCAC. Data revealed durable complete responses (CRs) in 2 patients; 1 patient had an ongoing response beyond 2 years, another had a sustained response for 15 months, and a third patient experienced an ongoing response at 64 weeks. The median duration of response (DOR) was 15.5 months with the experimental combination compared with 9.5 months with the current standard of care in this population.

Developers plan to convene with the FDA based on these findings and discuss a possible single-arm study intended to facilitate accelerated approval for the pelareorep regimen among patients with SCAC in the second line and beyond. The launch of this trial is anticipated in the first half of 2026.

“This is the most encouraging efficacy signal with a non-[chemotherapy] regimen we have ever seen in anal cancer. Achieving a 30% [ORR]—more than double the benchmark of the only approved immunotherapy—along with multiple responses lasting more than a year, including 2 [CRs], underscores pelareorep’s ability to unlock deep and durable immune responses,” Jared Kelly, chief executive officer at Oncolytics Biotech, stated in the press release.¹ “We believe the data represent our best chance to obtain an accelerated approval in a rare disease with virtually no options outside of chemotherapy.”

Investigators previously presented preliminary safety and tumor response data for the relapsed anal carcinoma cohort of the GOBLET trial at the 2025 ASCO Gastrointestinal Cancers Symposium.² Initial findings showed an ORR of 33%, which included 1 CR.

Regarding safety, the most common grade 3 or higher treatment-emergent adverse effects (TEAEs) following treatment with pelareorep plus atezolizumab included disease progression (16.7%), anemia (11.1%), aspartate aminotransferase increases (11.1%), cholestasis (11.1%), and pyrexia (5.6%). Additionally, 2 patients experienced grade 5 AEs, both of which were disease progression.

Translational data showed that pelareorep plus atezolizumab yielded the expansion of new and pre-existing tumor-infiltrating lymphocyte (TIL) clones among evaluable patients with a response. Additionally, the combination correlated with the upregulation of multiple chemokines including CLCL9, CLCL10, CLCL11, and PD-L1.

Investigators of the open-label, non-randomized, phase 1/2 GOBLET trial assessed treatment with pelareorep across different cohorts of patients with advanced or metastatic gastrointestinal cancers. Patient populations included those with frontline metastatic pancreatic ductal adenocarcinoma (PDAC) in cohort 1, first-line metastatic mismatch repair deficient colorectal cancer (CRC) in cohort 2, third-line metastatic CRC in cohort 3, second-line or later unresectable anal cancer in cohort 4, and first-line metastatic PDAC in cohort 5.

Patients included in cohort 4 of the trial received pelareorep at 4.5 x 10¹⁰ TCID₅₀ per dose intravenously on days 1, 8, 15, and 22 of each 28-day cycle plus atezolizumab at 840 mg intravenously on days 2 and 16. The trial’s primary end point was ORR. Secondary end points included safety, progression-free survival, and overall survival.

Patients 18 years and older with confirmed advanced or metastatic unresectable SCAC and progression on or intolerance of prior systemic chemotherapy were eligible for enrollment on the trial. Other eligibility criteria included having an ECOG performance status of 0 or 1, a measurable lesion per RECIST v1.1 guidelines, and no prior treatment with immune checkpoint inhibitors.

References

1. Oncolytics Biotech® reports updated anal cancer data showing objective response rate more than double the current standard of care. News release. Oncolytics Biotech Inc. October 28, 2025. Accessed October 28, 2025. https://tinyurl.com/2bfsr99x
2. Modest D, Goekkurt E, Heineman T, et al. Preliminary safety and tumor response results for the relapsed anal carcinoma cohort in patients treated with pelareorep and atezolizumab. J Clin Oncol. 2025;43(suppl 4):6. doi:10.1200/JCO.2025.43.4_suppl.6