A multicenter randomized phase II study of trastuzumab biosimilar (CT-P6) and chemotherapy (SOX or CapeOX) in HER2-positive advanced/recurrent gastric cancer (KSCC: TROX study).

4029 Background: The efficacy and safety of the trastuzumab biosimilar (CT-P6) combined with S-1/oxaliplatin (SOX) or capecitabine/oxaliplatin (CapeOX) were investigated in patients with HER2-positive advanced or recurrent gastric cancer who had not previously received chemotherapy. CT-P6 is a biosimilar of trastuzumab, which has demonstrated comparable safety and efficacy to trastuzumab in breast cancer. However, no clinical trials have evaluated CT-P6 in gastric cancer to date. Methods: This randomized, open-label, multicenter phase II study enrolled patients with HER2-positive unresectable or recurrent gastric cancer. Participants were randomized to receive SOX plus trastuzumab biosimilar therapy (S-1 orally, 40–60 mg twice daily for 14 days every 3 weeks, oxaliplatin intravenously at 130 mg/m² on day 1 every 3 weeks, and CT-P6 at 8 mg/kg on day 1 and 6 mg/kg every 3 weeks thereafter) or CapeOX plus trastuzumab biosimilar therapy (replacing S-1 with capecitabine [1,000 mg/m²] as described above) until disease progression. The primary endpoint was overall response rate (ORR) in both arms, with a null hypothesis response rate set at 43%, the lower bound of the 90% confidence interval reported in previous trastuzumab trials. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Results: Between May 2019 and November 2022, 67 patients were enrolled in the study. Patient characteristics were as follows: male/female ratio of 49/18, median age 68 years (range: 34–80), and performance status (PS) of 0/1 in 53/14 patients. The ORR was 76.1% (90% CI: 67.6–84.7%), with the lower limit of the confidence interval exceeding the threshold response rate of 43%, confirming the efficacy of trastuzumab biosimilar therapy. The one-year survival rate was 65.2% (95% CI: 49.8–78.6%), meeting the primary endpoint. The median OS was 18.7 months (90% CI: 15.1–23.1), and the median PFS was 9.0 months (90% CI: 6.5–10.7). Although the study was not designed to compare SOX and CapeOX, the response rate was slightly higher in the CapeOX group (81.3% [90% CI: 69.9–92.6%]) compared to the SOX group (71.4% [90% CI: 58.9–84.0%]). Similarly, OS was slightly better in the CapeOX group (22.3 months [90% CI: 15.1–42.1]) than in the SOX group (16.7 months [90% CI: 12.7–19.6]). The most frequent grade 3 or 4 adverse events were neutropenia (15.2%), appetite loss (12.1%), and diarrhea (7.6%). Conclusions: Trastuzumab biosimilar (CT-P6) combined with SOX or CapeOX demonstrated robust antitumor efficacy and manageable toxicity in patients with advanced or recurrent gastric cancer. Clinical trial information: jRCTs071190007 .