AbstractA multicenter, single-arm, open-label Phase I study of AN1004 (Pelareorep) oncolytic virus plus paclitaxel in Chinese patients with Hormone receptor-positive and HER2-negative advanced/metastatic breast cancer (REO 026-1) Background: AN1004, also known as Pelareorep is an intravenously delivered immuno-oncolytic unmodified reovirus being evaluated to treat multiple malignancies. AN1004 was shown to be safe and well-tolerated in both monotherapy and combination therapy in multiple clinical trials in North American and European populations, including two completed and two ongoing breast cancer studies. The completed phase 2 study (NCT01656538) in advanced/metastatic breast cancer demonstrated improved median overall survival (OS) in Canadian patients treated with AN1004 plus paclitaxel (PTX) versus PTX alone, and the greatest benefit in OS was observed in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) subtype. Since there has been no clinical trial assessing AN1004 in Chinese population, a bridging study (REO 026-1) was initiated to evaluate its safety and tolerability in combination with PTX in Chinese patients with HR+/HER2- advanced/metastatic breast cancer. Methods: Eligible Chinese patients must be female with good performance status (ECOG PS: 0 or 1), have had histopathological diagnosis with HR+/HER2- advanced/metastatic breast cancer, and were previously treated with at least one endocrine therapy with no more than one line of chemotherapy regimen for recurrent/metastatic disease. Patients are intravenously infused with AN1004 at escalating dose levels of 1.5 × 10^10 (Dose Level 1, DL1 group), 3 × 10^10 (DL2 group) and 4.5 × 10^10 TCID50 (DL3 group) on days 1, 2, 8, 9, 15, and 16 every 28 days plus PTX 80 mg/m^2 intravenously on days 1, 8, and 15 every 28 days. Three to six patients will be enrolled in the DL1 group, and 6 patients will be enrolled in each of the DL2 and DL3 groups. The primary objective is to assess the safety and tolerability of AN1004 in combination with PTX. A secondary objective is to evaluate the preliminary activity of AN1004 and PTX combination therapy. Results: By the data cutoff date of June 2nd, 2022, a total of 10 female patients were enrolled, with a median age of 58 years (range 36-67). Two (20%) patients had failed more than one prior line of endocrine therapy for advanced/metastatic disease, and 3 (30%) patients were previously treated with a CDK4/6 inhibitor. Three patients were treated with AN1004 and PTX in DL1 group; six patients were treated in DL2 group; one patient was treated in DL3 group. The most common (>50%, and/or liver function related) treatment emergent adverse events (TEAEs) included neutrophil count decreased and white blood cell count decreased (90% each), hypertriglyceridemia (70%), pyrexia, ALT increased and anemia (60% each), and AST increased (40%). Three (30%) patients had Grade 3 or above TEAEs, including neutrophil count decreased (30%), white blood cell count decreased (20%), hypertriglyceridemia, ALT increased and GGT increased (10% each). No serious AE or AE leading to treatment discontinuation was reported to date. One patient was not evaluable for dose-limiting toxicity (DLT) due to early withdrawal, and there were no DLTs observed in the 9 evaluable patients. Among the 10 treated patients, 2 (20%) patients achieved confirmed partial response (PR), 2 (20%) patients achieved unconfirmed PR, and 5 (50%) patients showed stable disease (SD). One patient in DL1 group achieved a confirmed PR and later progressed, and the other 8 patients who had PR or SD continue to receive treatment as of the data cut. Conclusion: To date, intravenous administration of AN1004 plus PTX is safe and well-tolerated in Chinese patients with advanced/metastatic breast cancer, and demonstrates anti-tumor activity.Citation Format: Wei Li, Yongmei Yin, Jiuwei Cui, Wenna Wang, Yan Liang, Hongming Liang, Binghe Xu. A multicenter, single-arm, open-label Phase I study of AN1004 (Pelareorep) oncolytic virus plus paclitaxel in Chinese patients with Hormone receptor-positive and HER2-negative advanced/metastatic breast cancer (REO 026-1) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-07-04.
