124P Neoadjuvant durvalumab plus endocrine therapy following immune-attractant exposure for early-stage ER+/HER2- breast cancer

ER+/Her2- breast cancer (BC) is associated with lower rate of Tumor-infiltrating lymphocytic (TILs), especially CD8+ T cells. We hypothesized that attracting CD8+ T cells on the tumor site could sensitize ER+/Her2- BC to anti-PD(L)1. Post-menopausal patients (pts) with cT2-T4 (>3cm), N0 or N+, M0 BC and Luminal A tumor defined by IHC (grade I-II, ER+ ≥ 60%, Ki67 <20%, and Her2-) have been enrolled to receive a single infusion of tremelimumab (3 mg/kg) with exemestane. After 3 weeks, pts with CD8+ T cells >10% in the tumor were enrolled in the part 2 and treated for 6 months with durvalumab 1500 mg Q4W IV and exemestane. The primary objective was the pathological response (pCR) at surgery in the CD8+ T cells enriched population. Out of the initially 96 pre-screened pts, 61 were included in part 1. Of them, 24 (39.3%) with CD8+ T cell >10% in the tumor after 3 weeks were enrolled in part 2: median age 66 years (61-71), lobular type 7 pts (29.2%), T3 or T2 tumours in 18 (75.0%) and 6 (25.0%) patients, respectively, 16 (66.7%) with N0 disease. Among the 22 pts evaluable for pCR, 1 pt (4.6%; CI 95%: 0.2% - 19.8%) achieved a pCR. The futility criterion was met and the study was stopped. An increase in CD8+T cells by 10.8% (95% CI: 6.8 – 14.7) and 4.8% (95% CI: 0.7 – 8.9) was observed between baseline and week 3 and surgery, respectively. Mean Ki67 level decreased by 6.0% (95% CI: -8.8; -3.3) and 7.0% (95% CI: -10.5; -3.4) between baseline and week 3 and surgery, respectively. TILs increased by 4.7% (95% CI: 0.7 – 8.6) and 3.8% (95% CI: -0.4 – 8.0) between baseline and week 3 and surgery, respectively. During part 1, 38 pts (22%) experienced adverse events (AEs), including 6 (15.8%) grade 3 AEs (colitis and liver enzyme elevation). In part 2, 20 pts (83.3%) developed AEs including 9 (45%) grade 3. Main grade 3 AEs included diarrhea, hypothyroidism, liver enzyme elevation and 1 pneumonitis. Despite an encouraging increase in CD8+ T cells, durvalumab combined with exemestane did not demonstrate significant efficacy, as indicated by the low pCR rate. Ongoing ancillary studies may provide further insights into the immune landscape and potential refinements for future trials.