Phase Ib study of intratumoral talimogene laherparepvec (T-VEC) in combination with chemotherapy or endocrine therapy in patients with advanced HER2-negative breast cancer

Talimogene laherparepvec (T-VEC) is an oncolytic virus that is hypothesized to enhance responses to systemic therapy. This Phase 1b trial evaluated the safety and efficacy of intratumoral T-VEC plus chemotherapy (CT) or endocrine therapy (ET) for patients with hormone receptor positive (HR + )/HER2- and triple negative (TN) advanced breast cancer (ABC) with injectable locoregional/chest wall disease. The primary endpoint was safety/tolerability. Secondary endpoints were objective response rate by irRECIST 1.1 and clinical assessment of local response. 19 patients enrolled (9 HR + /HER2-; 10 TN; median two lines of prior CT). Intratumoral T-VEC was administered with the following partners: gemcitabine/carboplatin (n = 8), nab-paclitaxel (n = 7), paclitaxel (n = 2), or ET (n = 2). Eight patients in the T-VEC + gemcitabine/carboplatin arm were formally evaluated for dose limiting toxicities (DLTs) based on pre-specified protocol criteria, and one DLT (grade 3 neutropenia leading to carboplatin dose reduction) was identified. Response per irRECIST 1.1 was evaluated in 16 patients: partial response (n = 2, 12.5%), stable disease (n = 7, 43.8%), progressive disease (n = 7, 43.8%). Patients with higher pre-treatment tumor infiltrating lymphocytes (TILs) were more likely to respond, and clinical responders had induction of Ki-67 in multiple peripheral myeloid populations. In conclusion, the addition of intratumoral T-VEC to CT or ET was safe in patients with ABC and injectable locoregional disease, supporting the continued investigation of direct intratumoral immunomodulatory strategies that can enhance local and systemic immune responses. NCT03554044.