Abstract P2-14-13: Talimogene laherparepvec (T-VEC) + atezolizumab combination in early breast cancer (SOLTI-1503 PROMETEO): Safety and efficacy interim analysis
Authors: Pascual Tomás , Vidal Maria , Oliveira Mafalda , Cejalvo Juan M , Vega Estela , Sanfeliu Esther , Ganau Sergi , Julve Ana , Zamora Esther , Miranda Ignacio , Delgado Ana , Bermejo Begoña , de la Cruz Luis , Falato Claudette , Juan Manel , Ferrero-Cafiero Juan M , González-Farré Xavier , Villagrasa Patricia , Prat Aleix 
Published: March 2022

Background Residual disease (RD) following neoadjuvant chemotherapy (NAC) in early HER2 negative breast cancer (BC) remains an unmet medical need. We hypothesized that combining T-VEC with Atezolizumab may offer clinical benefit in terms of residual cancer burden (RCB) rate in the pre-operative setting for patients with early BC with intermediate to high risk of recurrence who present RD after standard NAC. Methods SOLTI-1503 PROMETEO is an open-label, multicenter trial of T-VEC + Atezolizumab in patients with RD after completing standard NAC. Overall, 30 women with triple-negative BC (TNBC) or Luminal B-like/HER2-negative BC are planned to be included in the trial. RD must be confirmed by core-biopsy and tumor should have a diameter ≥ 10 mm measured by magnetic resonance imaging (MRI). Adequate organ function and ECOG PS 0-1 are required. T-VEC is administered intratumorally on week 1 (106 plaque-forming units/mL [pfu/mL]), then in week 4 and every 2 weeks thereafter (108 pfu/mL) for 4 injections. Atezolizumab (840 mg) is administered intravenously every 2 weeks for 4 infusions, starting at week 4. BC surgery is performed 1 to 3 weeks after completing the treatment. The primary objective is to evaluate the efficacy of the combination, measured by the rate of RCB class 0/1 at surgery. Secondary endpoints include rate of pCR, objective response rate (ORR; rate of complete response + partial response) assessed by MRI, safety, and the increase of mean expression of a gene signature tracking activated CD8+ T-cells. Here we present the safety and efficacy results of the interim analysis including the first 10 enrolled patients. Results: As of April 2021, 10 patients received the study treatment and were evaluable for primary endpoint and safety. Main patient characteristics were: median age 48 (37-71), ECOG PS 0 (70%) and post-menopausal (60%). Four patients had TNBC and 6 Luminal B-like BC; 5 patients had stage II BC and 4 stage III; 7 tumors were grade II and 3 were grade III; median Ki-67 was 44% (20-75). Mean tumor size by MRI after NAC was 30.5 mm (11-75). At surgery, one patient achieved RCB0. Two patients achieved an objective response, five patients a stable disease and disease progression was observed in three patients (2 TNBC and 1 Luminal-like tumor). Nine patients reported AEs. Only grade 1-2 adverse events were reported, being the most common Fever (n=6) Arthralgia ((n=4) AST increased (n=3) and ALT increased (n=3). Conclusion: The treatment of T-VEC and atezolizumab was feasible at the approved doses and the safety profile was consistent with that previously reported. One patient achieved RCB0. After the efficacy and safety analysis of the first 10 patients, it was decided to continue with the inclusion of up to 30 patients. Correlative analysis including gene expression analysis and centralized Tumor-infiltrating lymphocytes (TILs), PD-L1 (SP142) IHC will be presented.

Citation Format: Tomás Pascual, Maria Vidal, Mafalda Oliveira, Juan M Cejalvo, Estela Vega, Esther Sanfeliu, Sergi Ganau, Ana Julve, Esther Zamora, Ignacio Miranda, Ana Delgado, Begoña Bermejo, Luis de la Cruz, Claudette Falato, Manel Juan, Juan M Ferrero-Cafiero, Xavier González-Farré, Patricia Villagrasa, Aleix Prat. Talimogene laherparepvec (T-VEC) + atezolizumab combination in early breast cancer (SOLTI-1503 PROMETEO): Safety and efficacy interim analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-14-13.