A multicenter phase II randomized trial of durvalumab (D) versus physician’s choice chemotherapy (PCC) in patients (pts) with recurrent ovarian clear cell adenocarcinoma (MOCCA/APGOT-OV2/GCGS-OV3).
Authors: Tan David Shao Peng , Choi Chel Hun , Ngoi Natalie , Sun Haoyang , Heong Valerie , Ow Samuel Guan Wei , Chay Wen Yee , Kim Hee Seung , Lim Yi Wan , Goss Geraldine , Goh Jeffrey C. , Luo Vilianty , Tai Bee Choo , Lim Diana , Kaliaperumal Nivashini , AU Veonice Bijin , Connolly John , Kim Jae-Weon , Friedlander Michael , Kim Kidong 
Published: June 2022

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Background: The optimal treatment of recurrent ovarian clear cell carcinoma (rOCCC) remains unknown. Prior data suggests rOCCC is a chemo-resistant disease that may respond to programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint inhibition (ICI). We aimed to determine the efficacy of D versus PCC in pts with rOCCC. Methods: In this multicentre, open-label, randomised phase 2 trial, 9 academic centres across Singapore, South Korea and Australia, enrolled rOCCC (determined histologically) and Eastern Cooperative Oncology Group performance status (PS) 0-2 pts, who had recurred after prior platinum-based chemotherapy and had not received more than 4 prior lines of systemic therapy, nor prior ICI therapy. Eligible pts were randomly assigned (2:1), using dynamic block randomization with block size of 6, and stratification by ECOG PS, to receive D (1500mg on day 1, in 28-day cycles) or PCC until disease progression (PD), intolerable toxicity or withdrawal of consent. Pts with PD on PCC were allowed to crossover to D. The primary endpoint was investigator-assessed progression-free survival (PFS) by RECIST version 1.1 and analyses included pts who had commenced at least 1 cycle of study treatment. Results: Between 7 Nov 2017 and 17 Feb 2020, 57 pts were assessed for eligibility, of whom 47 (PS 0-1) were randomly assigned to treatment with D (31 pts) or PCC (16 pts). At the data cut-off date (10 Jan 2022), the median follow-up was 83.0 weeks (IQR: 54.1—97.0) in the PCC group and 107.0 weeks (IQR: 82.7—116.4) in the D group. Median PFS was 7.4 weeks (IQR: 6.0—16.0) in the D group and 14.0 (IQR: 7.0—28.6) in the PCC group (HR 1.5 [95% CI 0.8-2.8], log-rank p = 0.89). The objective response rate (ORR) was 10.7% in pts randomised to D and 18.8% in the PCC group (p = 0.884). Clinical benefit rate (CR/PR/SD for ≥16weeks) was similar for PCC (37.5%) and D (32.1%) (p = 0.756). 9 pts on PCC crossed over to receive D, with 2 of the 8 evaluable pts achieving partial response (PR). When crossover D pts were included, ORR to D was 13.9% (5/36) with a clinical benefit rate of 30.6% (11/36). Median duration of response was 44 weeks for the 3 PCC responders (PR to gemcitabine 24.9wks, PR to liposomal doxorubicin 65.7wks, CR to carboplatin/liposomal doxorubicin 44wks), and 18 weeks (range 2.1-45.3) for the 5 responders to D. Frequency of adverse events (AEs) across all grades was 68.8% for PCC and 38.7% for D. Grade 3/4 AEs were observed in 37.5% of PCC pts and 9.7% of D pts. Conclusions: No significant differences in PFS, ORR or clinical benefit rate were observed between D and PCC treatment in rOCCC. Treatment with D was associated with less grade 3-4 adverse events. Correlative translational analyses to elucidate predictive biomarkers of response and resistance are ongoing. Clinical trial information: NCT03405454.