Phase Ib INEOV neoadjuvant trial of durvalumab +/- tremelimumab with platinum chemotherapy for patients (pts) with unresectable ovarian cancer (OC): Survival outcomes and immune correlates.

5569 Background: Ineov was a phase Ib randomized trial of neoadjuvant carboplatin/paclitaxel (NACT) + durvalumab (D) +/- tremelimumab (T) in unresectable OC. We previously reported safety and encouraging complete resection rates (CC0=70%) and complete pathological response rates (pCR=18%) at interval debulking surgery (IDS). However there were no significant differences with the addition of T to D+NACT. Here we report survival outcomes and immune correlates with a focus on long-term responders. Methods: Pts with unresectable stage IIIC/IV OC were randomized to NACT + D (1125mg) alone (arm A) or with T (75mg once at C2) (arm B). IDS was planned after C3, or delayed after C6. Pts in arm A not operable after C3 crossed over to arm B, pts in arm B crossed over to standard of care (SOC) and assessed for delayed IDS after C6. PFS was assessed by Kaplan-Meier and PFS compared between arms A and B by Log-Rank test. Intra-epithalial CD8+ lymphocytes were scored as nb/mm 2 and HLA-I expression was scored by H-score. Results: 70 patients were randomized to Arm A (N=36) or Arm B (N=34). 4 pts were replaced for early toxicity and one early death attributed to COVID. Median PFS in all pts was encouraging at 18mo but not different between arms. CCO at IDS was associated with significantly improved PFS (mPFS 25mo vs 14mo; p 0.0008). NACT+D+/-T significantly increased intra-epithelial CD8+ infiltration (p40months. When compared to the other patients in the trial, this subset of long-responders was characterized by higher pCR (38% vs 11%), higher CC0 rates (100% vs 66% ) but showed no differences in immune profile. Among pts with known BRCA status, 43% of long-responders had a BRCAm (vs 20%). Conclusions: NACT combined with immunotherapy resulted in encouraging CC0, pCR and PFS in pts with unresectable OC, however the addition of T to D did not improve immune infiltration or outcomes. Features associated with long response were pCR, CC0 and BRCAm, not immune features. Clinical trial information: NCT03249142 .