Evaluation of the effectiveness and safety of disitamab vedotin in HER2-expressing 2L recurrent or metastatic cervical cancer (r/mCC): Interim results of RC48-C018.
Authors: Guangwen Yuan, Guiling Li, Qingshui Li, Youzhong Zhang, Ruifang An, Jinwei Miao, Keqiang Zhang, Hongying Yang, Yi Huang, Ruixia Guo, Li Sun, An Lin, Junying Tang, Xiumin Li, Jianming Ying, Yun Ling, Yanan Wang, Haiwen Zhou, Jianmin Fang, Lingying Wu
Journal: Journal of Clinical Oncology (2024)

5528 Background: Disitamab Vedotin (DV) is a HER2-targeted antibody-drug conjugate (ADC), and is approved in HER2-expressing gastric cancer and locally advanced or metastatic urothelial carcinoma. HER2 also shows certain expression in Gynecological malignant tumors. A phase 2, open-label, multicenter basket design study (NCT04965519) is currently underway to evaluate the efficacy and safety of DV monotherapy in the treatment of HER2-expressing gynecologic malignancies. Methods: The cervical cancer cohort includes patients (pts) with recurrent/metastatic cervical cancer (r/mCC) who failed with at least one-line platinum-containing standard treatment and had HER2 immunohistochemistry ≥1+. Pts received DV monotherapy administered intravenously at a dose of 2 mg/kg every 2 weeks until disease progression or intolerable toxicity. The primary endpoint is the objective response rate (ORR). Secondary endpoints include duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: 25 r/mCC pts were enrolled and received at least one cycle of treatment. At baseline, the median age was 56 years (range: 35-66 years). The number of pts in the 2L, 3L, and 4L+ was 12(48%), 9 (36%), and 4 (16%), respectively. The majority of pts (n=16, 64%) had a baseline ECOG performance score of 1. 16 pts (64%) had squamous cell carcinoma as the baseline histological type, and 9 pts (36%) had adenocarcinoma. 10 pts (40%) had prior anti-PD-(L)1 therapy. As of Oct 31, 2023, the median follow-up was 8.67months (mo) (range 1.7-19.7). Among the 22 evaluable pts, the ORR was 36.4% (8/22), the confirmed ORR was 31.8% (7/22), the median time to response was 1.5 mo (range 1-3); the mDoR was 5.52 mo (95% CI: 2.10, NE). The DCR was 86.4% (19/22), and the mPFS was 4.37 mo (95% CI: 2.92, 6.90). The mOS was unmature (95% CI: 9.63, not available). 12-month OS rate was 66%(95%CI:35%,85%). Subgroup analysis showed ORRs of 20% (2/10), 50% (4/8), and 25% (1/4) in the 2L, 3L, and 4L+ pts, respectively; ORRs of 50% (6/12), 12.5% (1/8), and 0 (0/2) for pts with IHC scores of 1+, 2+, and 3+ respectively; ORRs of 42.9% (6/14) and 12.5% (1/8) for pts with squamous cell carcinoma and adenocarcinoma, respectively. Among all 25 enrolled r/mCC pts, the most common treatment-related AE included ALT increased (56%), AST increased (56%), and white blood cell count decreased (52%). Grade 3 or higher TRAEs included neutrophil count decreased (12%), ALT increased (8%). Two pts (8%) experienced treatment-related SAE. No DV-related deaths occurred. Conclusions: In the study, DV showed manageable safety and promising efficacy in HER2-expressing r/mCC pts who have failed from multiple lines of therapy. These results support further investigation for DV in r/mCC. Clinical trial information: NCT04965519 .