5520 Background: Heavily treated platinum-resistant ovarian cancer remains a therapeutic challenge. Although standard therapy includes non-platinum single agent chemotherapy (CT), prognoses are very poor in this setting. Anticancer therapies based on molecular biomarkers have improved dramatically. We report data from an umbrella study of biomarker-driven targeted therapy (olaparib, O; cediranib, C; durvalumab, D; tremelimumab, T) in platinum-resistant recurrent ovarian cancer (NCT03699449). Methods: Patients with platinum-resistant ovarian cancer with ≥ two lines of prior chemotherapy and ECOG 0/1 were eligible for this study. In the screening phase, archival tumor samples were tested for HRD and PD-L1 status. Treatment arms were allocated according to the test results. For HRD+ patients, we tested the synergistic effects of O with other agents: patients were randomly allocated to arm 1, O+C (O 200mg bid + C 30mg qd); or arm 2, O+D (O 300mg bid + D 1500mg q4w). For HRD- patients, we tested the role of biomarker-driven immunotherapy according to PD-L1 expression: arm 3, D+CT (D 1500mg q4w + PLD or topotecan or weekly paclitaxel [6 cycles]) in patients with high PD-L1 expression; arm 4, D+T75+CT (D 1500mg q4w + T 75mg q4w [4 doses] + PLD or topotecan or weekly paclitaxel [4 cycles]) in patients with low PD-L1 expression; or arm 5, D+T300+CT (D 1500mg q4w + T 300mg [1 dose] + weekly paclitaxel [60mg/m2 D1,8,15 q4w for 4 cycles]) in patients with low PD-L1 expression. Recruitment to arm 5 was initiated after completion in arm 4. The primary endpoint was objective response rates (ORR) according to RECIST 1.1. Results: Between Dec 2018 and Oct 2020, 70 patients were allocated to treatment as follows: arm 1 (n = 16), arm 2 (n = 14), arm 3 (n = 5), arm 4 (n = 18), and arm 5 (n = 17). Median age was 57 years (range 34-77) and median prior lines of treatment was 3 (range: 2-10). Among all patients, the ORR was 35.7% (25/70, 95% CI: 24.6%-48.0%); complete response was observed in two patients. The ORRs (95% CI) for each treatment arm were shown (Table). Treatment-related grade 3/4 adverse events were reported in 37.5%, 35.7%, 20%, 66.7%, and 35.3% of patients in each treatment arm, respectively. No treatment-related adverse events (TRAEs) leading to discontinuation of treatment and no grade 5 TRAEs were observed. Conclusions: This is the first biomarker-driven umbrella study conducted in patients with platinum-resistant recurrent ovarian cancer. This umbrella study provides preliminary evidence on the clinical benefit of biomarker-driven targeted therapy. All regimens were manageable, without unexpected toxicities. Clinical trial information: NCT03699449. [Table: see text]
OCTAVE: A phase I study of enadenotucirev, an oncolytic group B adenovirus, in combination with weekly paclitaxel in platinum-resistant epithelial ovarian cancer