Multicenter phase 1b-2 study of EMB-01 for heavily pretreated metastatic colorectal cancer

EMB-01 is a novel EGFR-cMET targeting bispecific antibody. A multicenter phase 1b-2 study in China evaluated EMB-01 in patients predominantly with heavily pretreated metastatic colorectal cancer (mCRC). EMB-01 was administered at 1600 mg intravenously weekly. Primary endpoints were safety and tolerability in phase 1b (n=27) and antitumor activity in phase 2 (n=25). All patients experienced at least one treatment-emergent adverse event, and 98.1% experienced treatment-related adverse events (TRAEs). Grade ≥ 3 TRAEs occurred in 63.5% of patients, with rash (25%) and dermatitis acneiform (17.3%) as the most frequent TRAEs. Among the 48 patients with mCRC, the confirmed objective response rate was 12.5% (95% CI 4.7-24.2) with a median duration of response of 32 weeks (16-NE). All responses were observed in a favorable mCRC subgroup of 29 patients with evaluable response (left-sided, RAS/RAF wild-type, naïve to fruquintinib/regrafenib/TAS-102). In this subgroup, the unconfirmed ORR was 24.1% (95% CI 10.3-43.5) and the confirmed ORR was 20.7% (8-39.7). Median progression-free survival was 19 weeks (95% CI 12.3-24.1). The authors conclude that EMB-01 demonstrated a manageable safety profile and promising antitumor activity in heavily pretreated mCRC, particularly in the RAS/RAF wild-type, left-sided mCRC subgroups naïve to late-line therapies.