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Clinical Trial
. 2023 Oct;11(10):e007444.
doi: 10.1136/jitc-2023-007444.

Phase II study of durvalumab and tremelimumab with front-line neoadjuvant chemotherapy in patients with advanced-stage ovarian cancer: primary analysis in the original cohort of KGOG3046/TRU-D

Junsik Park  1   2 , Jung Bok Lee  3 , Myong Cheol Lim  4 , Byoung-Gie Kim  5 , Jae-Weon Kim  6 , Sunghoon Kim  1 , Chel Hun Choi  5 , Hee Seung Kim  6 , Sang Yoon Park  4 , Jung-Yun Lee  7 ; KGOG investigators
Affiliations
Clinical Trial

Phase II study of durvalumab and tremelimumab with front-line neoadjuvant chemotherapy in patients with advanced-stage ovarian cancer: primary analysis in the original cohort of KGOG3046/TRU-D

Junsik Park et al. J Immunother Cancer. 2023 Oct.

Abstract

Background: This study assessed the antitumor activity and safety of durvalumab plus tremelimumab combined with neoadjuvant chemotherapy (NAC) in patients newly diagnosed with advanced ovarian cancer. Here, we report the primary endpoint of the original cohort of the KGOG 3046/TRU-D study.

Methods: In this investigator-initiated single-arm, phase II trial, patients with stage IIIC-IVB ovarian cancer were administered three cycles of durvalumab (1500 mg) and tremelimumab (75 mg) with NAC, followed by interval debulking surgery (IDS). After surgery, three cycles of durvalumab (1120 mg) and adjuvant chemotherapy followed by durvalumab maintenance (1120 mg [total 12 cycles]) were administered. The primary endpoint of the study was 12-month progression-free survival (PFS) rate.

Results: Twenty-three patients were enrolled. The median patient age was 60 years (range 44-77 years), and most patients presented with high-grade serous carcinoma (87.0%) and stage IV disease (87.0%). At the time of data cut-off on January 17, 2023, the median follow-up duration was 29.2 months (range 12.0-42.2). The 12-month, 24-month, and 30 month PFS rates were 63.6%, 45.0%, and 40.0%, respectively. All patients underwent IDS, with an R0 resection rate of 73.9%, and 17.4% achieved pathological complete response. Skin rashes were the most common treatment-related adverse events (TRAEs, 69.6%). However, all TRAEs completely resolved after steroid use.

Conclusion: This study showed promising activity with a durable clinical response, supporting the potential of NAC with dual immune checkpoint blockade in advanced-stage ovarian cancer.

Trial registration number: NCT03899610.

Keywords: clinical trials, phase II as topic; immune checkpoint inhibitors; immunotherapy; programmed cell death 1 receptor.

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Conflict of interest statement

Competing interests: J-YL, B-GK and J-WK report grants from AstraZeneca during the conduct of the study. J-YL reports grants and personal fees from Beigene, Bergenbio, Clovis Oncology, Immunogen, Janssen, Merck, MSD, Novartis, Roche, Seagen, Synthon, and Takeda. B-GK reports grants from MSD, Cellid, and Utilex. J-WK reports personal fees from AstraZeneca, Janssen, MSD, Takeda, GSK, Boryung, CMIC, LG Pharma, and Viflor Pharma. MCL reported having a consulting or advisory role for AstraZeneca, Boryung, CKD Pharm, Genexine, Hospicare, GI Innovation, and Takeda and receiving research funding from AbbVie, Amgen, Astellas, AstraZeneca, BeiGene, Cellid, CKD Pharm, Clovis, Eisai, Genexine, GSK, Incyte, Merck, MSD, OncoQuest, Pfizer, and Roche.

Figures

Figure 1
Figure 1
Trial flow diagram. D, durvalumab; ITT, intentionion-to-treat; NAC, neoadjuvant chemotherapy; T, tremelimumab.
Figure 2
Figure 2
PFS and overall survival in the modified ITT population. (A) PFS. The reference is assumed to have an exponential survival distribution and a median PFS of 12 months. (B) Overall survival. (C) A swimmer plot showing outcomes in all patients from the start of treatment to either disease progression or the date of last-follow-up. CR, complete response; ITT, intention-to-treat; PFS, progression-free survival.
See this image and copyright information in PMC

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