LAUSR

Background: Immunotherapy has emerged as a novel therapeutic strategy in many solid malignancies. In breast cancer, treatment with checkpoint inhibitors alone showed minimal response rates, likely because breast cancers are not sufficiently immunogenic to induce adequate baseline T cell activation. Talimogene laherparepvec (T-VEC) is an attenuated herpes simplex virus 1 (HSV-1) engineered to introduce the GM-CSF gene selectively into tumor cells to thereby enhance the immunogenicity of transduced tumor cells. T-VEC has been approved in the treatment of patients with advanced melanoma and injectable tumors. In a phase 1b clinical trial, T-VEC was well tolerated in combination with immunotherapy in patients with advanced melanoma. We evaluated the safety and tolerability of T-VEC, nivolumab, and ipilimumab in the preoperative treatment of early stage localized triple-negative breast cancer (TNBC) and hormone receptor (HR)-positive breast cancer. Trial design and eligibility criteria: This is a single site open-label phase 1b window of opportunity trial of neoadjuvant T-VEC in combination with nivolumab and ipilimumab in patients with localized breast cancer. Twenty patients with localized TNBC or HR-positive breast cancer with palpable tumors will be included. T-VEC is administered intratumorally in week 1 (106 plaque-forming units/mL [pfu/ml]) and then every 3 weeks (108 plaque-forming units/mL [pfu/ml]) for a total of 3 injections. Nivolumab (240 mg) is administered intravenously in week 1 and every 2 weeks for a total of 4 infusions. Ipilimumab (1 mg/kg) is administered intravenously in week 1 and week 6 for a total of 2 infusions. Breast cancer surgery will be carried out after completion of study treatment. Neoadjuvant chemotherapy could be administered before or after study treatment. Study objectives: The primary objective is to evaluate the safety and tolerability of T-VEC in combination with nivolumab and ipilimumab in this population. The secondary objectives are 1) to assess tumor response to T-VEC, nivolumab, and ipilimumab and 2) to descriptively analyze surgical specimens for evidence of tumor necrosis and inflammatory infiltration on histopathological examination. Present accrual: To date, 5 patients have been enrolled. As described above, the projected sample size is 20 patients. Clinical trials identification: NCT04185311 Citation Format: Vina P. Nguyen, Helena R. Chang, Maggie L. DiNome, Denise K. Oseguera, Deborah J. Wong, Anthony T. Nguyen, Stephen L. Shiao, John A. Glaspy. A phase I study of preoperative ipilimumab, nivolumab, and talimogene laherparepvec for localized breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-13-01.