Long-term outcomes in triple-negative breast cancers (TNBC) treated with talimogene laherparepvec (TVEC) in combination with neoadjuvant chemotherapy (NACT).

598 Background: TVEC is an engineered herpes simplex oncolytic virus (HSV OV) approved for the treatment of melanoma. We published a phase 1/2 trial combining TVEC with NACT in early stage TNBC demonstrating increased pathologic complete response (pCR) compared to expected rates with NACT. We are presenting updated long term follow up data on this cohort of both phase 1 and 2 evaluable patients. Methods: Stage II-III TNBC pts were enrolled into a single arm, optimal phase 1/2 trial with TVEC (10^6 PFU 1 st dose then 10^8 PFU x 4 doses) weeks 1,4,6,8,10 + weekly paclitaxel (80mg/m2) IV x 12, followed by dose dense AC (doxorubicin/cyclophosphamide 60/600 mg/m2) IV q2weeks x 4 alone (wT-AC) given preoperatively. Primary endpoint was pCR rate. Secondary endpoints included 5 year disease free survival/overall survival rates (DFSR/OSR), safety, immune correlates. Results: Forty six patients were enrolled at Moffitt (5/2018 – 4/2020) and evaluable for response and outcomes. Study demographics: median age 49 (27-66), 69.5% White, 13% Black, 13% Hispanic, clinical stage II 80% and III 20%, node + 45%. The pCR rate for the phase 1/2 cohort was 45.6% (95% CI 30.9-60.9). Additionally, 10 patients had residual cancer burden (RCB) 1 responses (associated w/ favorable outcomes) 21.7% (95% CI 10.9-36.3%). At median follow up of 70 months (range 17-98), six patients have had a breast cancer recurrence DFSR=86.9% (95% CI 73.7-95.0) and four patients died OSR=91.3% (95% CI 79.2-97.6). DFSR in pCR group = 95.2% (95% CI 76.1 – 99.9) and non-pCR group = 80% (95% CI 59.3 – 93.1%). All but one of the recurrences occurred in patients with non-PCR responses (RCB 2-3) to TVEC+NACT. Clinical stages at presentation for patients with recurrences were 5 stage II and 1 stage III. No patients had any HSV reactivation or autoimmunity events during the post study surveillance period. Greater immune enrichment of B and T cell subsets in pCR vs. non-pCR tumors was observed during TVEC treatment. Conclusions: To our knowledge, this is the first report on longer term outcomes for early TNBC treated with OV. TVEC plus wT-AC demonstrates promising long term outcomes when compared to the more intensive KEYNOTE 522 checkpoint regimen. Additional investigation of oncolytic viruses administered during NACT for TNBC is warranted to confirm this benefit. Clinical trial information: NCT02779855 .