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.

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.