Zanidatamab plus chemotherapy for first-line (1L) treatment of HER2+advanced or metastatic gastro-oesophageal adenocarcinoma (mGEA): New and updated data from a phase II trial

초록

Background In an ongoing phase 2 trial, zanidatamab (zani), a HER2-targeted bispecific antibody + chemotherapy (chemo) showed encouraging antitumour activity with a manageable safety profile in the 1L treatment of patients (pts) with HER2+ mGEA (prior data cut-off: Oct 2022). Here, we report new and updated results, including the latest overall survival (OS) data. Methods In this open-label phase 2 trial (NCT03929666), eligible pts (≥18 years with HER2-expressing mGEA) were treated with zani + physician’s choice of chemo (mFOLFOX6, CAPOX or FP). After the first 25 pts were enrolled, pretreatment with antidiarrhoeal prophylaxis was added for cycle 1. Endpoints included confirmed objective response rate (cORR), duration of response (DoR), progression-free survival (PFS), OS and rate/severity of adverse events (AEs). Results As of 17 Jan 2024, 46 pts were enrolled (zani + mFOLFOX6 [n=24], CAPOX [n=20] or FP [n=2]); 41 (89%) had tumours that were centrally confirmed as HER2+ mGEA (ccHER2+; IHC 3+/FISH+ [n=36; 78%] or IHC 2+/FISH+ [n=5;‍ 11%]). The median follow-up was 41.5 (range, 23.0-52.7) months; treatment was ongoing for 10 pts (22%) with 24 (52%) still on study. Among 37 response-evaluable pts with ccHER2+ mGEA, the cORR was 84% (95% CI: 68, 94); 4 achieved complete responses. The median DoR was 18.7 (95% CI: 8.3, not reached) months. Among all pts with ccHER2+ mGEA, the median PFS was 15.2 (95% CI: 9.5, 33.4) months. While median OS was not mature, the Kaplan-Meier–estimated 24-month OS was 65% (95% CI: 48, 78) and 30-month OS was 59% (95% CI: 41, 73). Grade ≥3 treatment-related AEs (TRAEs) occurring in ≥5% of all 46 pts enrolled in this study were diarrhoea (35%), hypokalaemia (22%), nausea (7%) and vomiting (7%). Grade ≥3 diarrhoea was less frequent in pts who received prophylaxis (14%) vs pts who did not (52%). Eight (17%) pts had serious TRAEs; there were no treatment-related deaths. Conclusions With >3.4 years of median follow-up, zani + chemo continues to show promising antitumour activity, with an encouraging OS, and a manageable safety profile for 1L treatment in pts with HER2+ mGEA. A global phase 3 HERIZON-GEA-01 is investigating zani + chemo ± tislelizumab for 1L treatment of HER2+ mGEA.