EMB-01, an Anti-EGFR/c-MET Bispecific Antibody, in Patients with Heavily Pretreated Metastatic Colorectal Cancer From a Phase Ib/II, Open-Label, Multicenter Study.

Purpose EMB-01 is a novel EGFR × c-MET bispecific antibody. The phase Ib/II study (NCT05176665) presents the safety and antitumor activity of EMB-01 in patients predominantly with heavily pretreated metastatic colorectal cancer (mCRC). Patients and methods EMB-01 was administered at 1600 mg intravenously weekly. Primary endpoints were safety and tolerability in phase Ib, and antitumor activity in phase II.

Secondary endpoints included cross-phase validation of antitumor activity and safety. Exploratory endpoints included biomarker analysis. Results Fifty-two patients were enrolled (phase Ib, n=27; phase II, n=25). All patients (100%) experienced at least one treatment-emergent adverse event (TEAE), and 98.1% experienced treatment-related adverse events (TRAEs).

Grade ≥ 3 TRAEs occurred in 63.5% of patients, with rash (25.0%) and dermatitis acneiform (17.3%) most frequently. Among the 48 mCRC patients, the confirmed objective response rate (cORR) was 12.5% (95% confidence interval [CI], 4.7 to 25.2%), with a median duration of response (DOR) of 32.0 weeks (95% CI, 16.0 to not estimable). All responses were observed in a favorable mCRC subgroup with evaluable response (left-sided, RAS/RAF wild-type, naïve to fruquintinib/regorafenib/trifluridine-tipiracil [TAS-102]; n=29). In this subgroup, the unconfirmed ORR (uORR) and the cORR were 24.1% (95% CI, 10.3 to 43.5%) and 20.7% (95% CI, 8.0 to 39.7%), respectively.

Median progression-free survival (mPFS) was 19.0 weeks (95% CI, 12.3 to 24.1 weeks). Conclusions 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 subgroup naïve to late‑line therapies, warranting further clinical development.