Durvalumab with or without tremelimumab plus chemotherapy in HRR non-mutated, platinum-resistant ovarian cancer (KGOG 3045): A phase II umbrella trial.
In: Gynecologic Oncology, Jg. 182 (2024-03-01), S. 7-14
academicJournal
Zugriff:
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. 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). 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. Dual immunotherapy with chemotherapy showed acceptable response rates and tolerable safety in HRR non-mutated PROC, warranting continued clinical investigation. • Efficacy and safety of chemotherapy plus durvalumab with or without tremelimumab were studied in PROC without HRR mutation. • Addition of tremelimumab improved progression-free survival on multivariable Cox HR analysis. • Biomarkers were explored with immunohistochemistry and whole-exome and transcriptome sequencing. • Mutation in MUC16 and high EPCAM were associated with favorable response in the overall cohort. • Arm-specific biomarker in tremelimumab group were EPCAM expression and matrix remodeling score. [ABSTRACT FROM AUTHOR]
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Durvalumab with or without tremelimumab plus chemotherapy in HRR non-mutated, platinum-resistant ovarian cancer (KGOG 3045): A phase II umbrella trial.
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Autor/in / Beteiligte Person: | Kim, Se Ik ; Joung, Je-Gun ; Kim, Yoo-Na ; Park, Junsik ; Park, Eunhyang ; Kim, Jae-Weon ; Lee, Sungyoung ; Lee, Jung Bok ; Kim, Sunghoon ; Choi, Chel Hun ; Kim, Hee Seung ; Lim, Jinyeong ; Chung, Jongsuk ; Kim, Byoung-Gie ; Lee, Jung-Yun |
Zeitschrift: | Gynecologic Oncology, Jg. 182 (2024-03-01), S. 7-14 |
Veröffentlichung: | 2024 |
Medientyp: | academicJournal |
ISSN: | 0090-8258 (print) |
DOI: | 10.1016/j.ygyno.2023.12.029 |
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