RE:IreneFull Abstracts minus embargoed_FINAL.pdf
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P1-09-19: IRENE study: Phase 2 study of oncolytic virus pelareorep and PD-1 inhibitor retifanlimab in metastatic triple negative breast cancer Presenting Author(s) and Co-Author(s): Mridula George, Mridula A. George, Nicole O. Williams, Coral Omene, Danielle Tang, Shou-En Lu, Matt Coffey, Thomas Charles Heineman, Shridar Ganesan, Deborah Toppmeyer Abstract Number: SESS-2300 Background Treatment with checkpoint inhibitors has clinical benefit in PD-L1 positive metastatic triple negative breast cancer (mTNBC). However only 40-50% of mTNBC tumors have PD-L1 expression. Pelareorep, a proprietary isolate of the unmodified replication competent reovirus type 3 Dearing (T3D) strain, a non-enveloped reovirus has been shown to upregulate PD-L1 expression in tumor and inflammatory cells and promote a favorable CD8:regulatory T-cell ratio indicating a less immunosuppressive tumor microenvironment. We hypothesized that the treatment with pelareorep will improve the response rates in patients with metastatic triple negative breast cancer by priming the tumor microenvironment for enhanced tumor response to PD-1 inhibitor retifanlimab. Methods This was a phase II multi-site, single-arm clinical trial to study the combination of the oncolytic virus pelareorep and PD-1 inhibitor retifanlimab in patients with mTNBC. Patients with PD-L1 positive and PD-L1 negative tumors were eligible for the study. Eligible patients received 1-2 prior lines of therapy in the metastatic setting. Patients who received prior immunotherapy were also eligible for the study. Eligible patients received pelareorep 4.5x1010 TCID50 / day intravenous (IV), on Days 1, 2, 15 and 16 and retifanlimab 500 mg IV on day 3 of every 28-day cycle. (ClinicalTrials.gov Identifier: NCT04445844) Primary endpoint was objective response rate (ORR) and safety, as determined by the number, frequency, duration, and severity of AEs using CTCAE v5.0. The study was designed using Simons optimal 2-stage design. In the first stage, 14 patients would be accrued. If there were 1 or fewer responses in these 14 patients, the study would be terminated. Otherwise, 11 additional patients would be accrued for a total of 25 patients. The null hypothesis would be rejected if 4 or more responses are observed in 25 patients. Results Fifteen patients were enrolled in the study (100% women). Median age was 58.6yrs. (66% White, 20% African American, 13% Asian). One patient withdrew from study due to grade 3 fatigue after C1D15. This patient was not included in the efficacy assessment. Of the fourteen evaluable patients in stage 1 of the study, one patient had partial response (ORR of 7.1%). Duration of response in this patient was 7 months. The average number of cycles for all patients was 2.18 cycles. Five patients received prior treatment with checkpoint inhibitors - pembrolizumab or atezolizumab. According to the protocol-specified analysis at the end of the stage 1, the efficacy objective (of atleast 2 objective response) was not met. Hence, the study was terminated at the end of stage 1. The combination was well tolerated. One patient had Grade 3 depressed level of consciousness, which was not related to pelareorep or retifanlimab. One patient with Grade 5 event, which was attributed to disease progression. Conclusion The combination of pelareorep and retifanlimab in patients with mTNBC did not show significant anti-tumor activity. One patient had a partial response. Tumor tissue, stool and blood samples collected during treatment will be assessed to understand the role of PD-L1 expression and gut microbiome, especially in the patient with response.