2-year follow-up of zanidatamab (Zani)+mFOLFOX6 ±bevacizumab (Bev) infirst-line(1L) treatment of patients(Pts) with human epidermal growth factor receptor 2-positive (HER2+) advanced/metastatic colorectal cancer (mCRC)

초록

Background: 1L treatment with zani, a dual HER2-targeted bispecific antibody, + mFOLFOX6 ± bev had encouraging preliminary antitumour activity (91% confirmed objective response rate [cORR]) with a generally manageable safety profile in pts with HER2+ mCRC. Here, we report updated antitumour activity and safety outcomes for the mCRC cohort after ∼2 years of follow-up. Methods: This phase II, open label trial (NCT03929666) evaluated 1L zani + mFOLFOX ± bev for pts with centrally confirmed HER2-expressing metastatic gastrointestinal cancer. Pts treated with prior HER2-targeted agents and >1 cycle of a fluorouracil (5-FU)-based regimen for mCRC were excluded. Eligible pts received zani (1200 mg [<70 kg]/1600 mg [≥70 kg] IV every 2 weeks) + mFOLFOX6-2 (leucovorin 400 mg/m2 IV and oxaliplatin 85 mg/m2 IV on days 1 and 15; 5-FU 1200 mg/m2/day IV on days 1-2 and 15-16) ± bev per physician’s choice (5 mg/kg IV on days 1 and 15). Results: Thirteen pts were treated (zani + mFOLFOX6-2, n=6; zani + mFOLFOX6-2 + bev, n=7). All pts had HER2+ tumours (IHC 3+/FISH+, 8 [62%]; IHC 2+/FISH+, 5 [38%]). As of 28 July 2024, the median (range) follow-up was 23.1 (11.2-26.9) months (mo). Ten (77%) pts remained on study (treatment ongoing, 7 [54%]; survival follow-up, 3 [23%]); 3 (23%) pts withdrew consent. The cORR was 100% (95% CI: 71.5, 100); all partial responses. The median duration of response (DOR) was not reached (NR; range: 6.8-25.2 mo). The median progression free survival (PFS) and overall survival (OS) were NR. The estimated 18-mo (95% CI) PFS and OS were 80% (39, 95) and 100% (not evaluable [NE], NE). The safety profile was consistent with the initial report; no treatment-related deaths. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 5 (38%) pts, 3 (23%) of whom reported diarrhoea. No pts discontinued zani due to a TRAE; 9 (69%) pts discontinued chemotherapy due to a TRAE (peripheral sensory neuropathy, n=9 [69%]; rash, n=1 [8%]). Conclusions: after ∼2 years of follow-up, zani + mFOLFOX6 ± bev continues to show encouraging antitumour activity (100% cORR) with prolonged survival and DOR and a generally manageable safety profile in pts with HER2+ mCRC.