A multicenter, open-label, single-arm, phase II trial to evaluate the efficacy and safety of geptanolimab (GB226) in the treatment of patients (pts) with programmed cell death ligand 1 (PD-L1)–positive recurrent or metastatic cervical cancer, for whom prior platinum-containing chemotherapy has failed.
Authors: An Jusheng , Zhang Yunyan , Feng Mei , Zhang Keqiang , Zhu Jianqing , He Aiqin , Li Xiumin , Peng Jin , Wang Xinwen , Zhang Hongping , Kong Weimin , Li Guiling , Yuan Jianlin , Yu Shiying , Liu Hu , Ma Cailing , Chen Hongmin , Shen Liangfang , Xie Fan , Wu Lingying 
Published: June 2023

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Background: Geptanolimab (GB226) is a novel anti-programmed cell death 1 (PD-1) antibody, exhibiting good tolerance and promising efficacy in pts with advanced/recurrent solid tumor/lymphoma in previous phase I/II studies. This study is a two-part, multicenter, single-arm phase II study of GB226 in pts with recurrent or metastatic cervical cancer recruited from 28 clinical sites in China. In Part 1, we observed encouraging antitumor activity of GB226 with 11 PRs in 46 PD-L1 positive (combined positive score, CPS≥1) pts. Here we report the efficacy and safety results from Part 2 of this trial. Methods: In part 2, PD-L1 positive (CPS≥1) pts with recurrent or metastatic cervical cancer who had received one or more lines of platinum-containing chemotherapy were enrolled and treated with GB226 (intravenous infusion, 3 mg/kg) once every 2 weeks until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR) assessed by Independent Review Committee (IRC) per RECIST 1.1. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety. Results: In Part 2, 123 pts were enrolled. As of July 28, 2022, after a median follow-up of 16.69 months (95%CI: 11.07, NR), 100 pts who met the study population criteria were eventually included in the full analysis set (FAS). 46% (46/100) of pts had received ≥2 lines of prior systemic therapy and 90% (90/100) had squamous cell carcinoma. The ORR was 18.0% (18/100; 95%CI: 11.03%, 26.95%) assessed by IRC, including 5 pts with CR (5.0%) and 13 pats with PR (13.0%); Median DOR was not reached (95%CI: 7.16, NR), median PFS was 1.91 months (95%CI: 1.87, 3.55), and median OS was 16.69 months (95%CI: 11.07, NR). Clinical benefit was observed across most patient subgroups, with a trend of higher ORR in pts with squamous cell carcinoma, no previous bevacizumab use and higher CPS. Among 123 safety-evaluable pts, 97 (78.9%) pts experienced a treatment-related adverse event (TRAE). The most common TRAE (≥10%) were hypothyroidism (24.4%), anemia (21.1%) and hyperthyroidism (13.8%), most of which were grade 1 and 2. Treatment-related grade 3/4 adverse events occurred in 25 (20.3%) and 2 (1.6%) pts, respectively. No grade 5 TRAEs occurred. 7 (5.7%) pts discontinued treatment due to a TRAE. The most common immune-related adverse events (irAE, ≥5%) were hypothyroidism 27 (22.0%) and hyperthyroidism 16 (13.0%). Conclusions: GB226 demonstrated durable antitumor activity and manageable safety profile in pts with recurrent or metastatic cervical cancer. Clinical trial information: NCT03808857 .