Phase 1b study of intratumoral tamilogene laherparepvec in combination with chemotherapy or endocrine therapy for advanced HER2-negative breast cancer

Tamilogene laherparepvec (T-VEC) is an oncolytic virus that may enhance responses to systemic therapy. A phase 1b trial at University of California San Francisco evaluated safety and efficacy of intratumoral T-VEC plus chemotherapy (CT) or endocrine therapy (ET) in patients with HR+/HER2- or triple-negative (TN) advanced breast cancer (aBC) with injectable locoregional/ chest wall disease. Nineteen patients were 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). Primary endpoint was safety/tolerability. One dose-limiting toxicity (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 pretreatment tumor infiltrating lymphocytes were more likely to respond, and clinical responders had induction of Ki-67 in multiple peripheral myeloid populations. The authors conclude that addition of intratumoral T-VEC to CT or ET was safe in patients with aBC and injectable locoregional disease.