Durvalumab with or without tremelimumab plus chemotherapy in HRR non-mutated, platinum-resistant ovarian cancer (KGOG 3045): A phase II umbrella trial

Abstract

Aim. We investigated the efficacy and safety of durvalumab (D) with or without tremelimumab (T) in addition to single -agent chemotherapy (CT) in patients with platinum -resistant recurrent ovarian cancer (PROC) lacking homologous recombination repair (HRR) gene mutations. Patients and methods. KGOG 3045 was an open -label, investigator -initiated phase II umbrella trial. Patients with PROC without HRR gene mutations who had received >= 2 prior lines of therapy were enrolled. Patients with high PD -L1 expression (TPS >= 25%) were assigned to arm A (D + CT), whereas those with low PD -L1 expression were assigned to arm B (D + T75 + CT). After completing arm B recruitment, patients were sequentially assigned to arms C (D + T300 + CT) and D (D + CT). Results. Overall, 58 patients were enrolled (5,18, 17, and 18 patients in arms A, B, C, and D, respectively). The objective response rates were 20.0, 33.3, 29.4, and 22.2%, respectively. Grade 3-4 treatment -related adverse events were observed in 20.0, 66.7, 47.1, and 66.7 of patients, respectively, but were effectively managed. Multivariable analysis demonstrated that adding T to D + CT improved progression -free survival (adjusted HR, 0.435; 95% CI, 0.229-0.824; P = 0.011). Favorable response to chemoimmunotherapy was associated with MUC16 mutation (P = 0.0214), high EPCAM expression (P = 0.020), high matrix remodeling gene signature score (P = 0.017), and low FOXP3 expression (P = 0.047). Patients showing favorable responses to D + T + CT exhibited significantly higher EPCAM expression levels (P = 0.008) and matrix remodeling gene signature scores (P = 0.031) than those receiving D + CT. Conclusions. Dual immunotherapy with chemotherapy showed acceptable response rates and tolerable safety in HRR non -mutated PROC, warranting continued clinical investigation. (c) 2024 Elsevier Inc. All rights reserved.