EMB-01, a tetravalent anti-EGFR/cMET bispecific antibody, in the left-sided, RAS/BRAF wild-type, late-line metastatic colorectal cancer: Subgroup analysis of baseline characteristics and response from a phase 1/2 study.

Abstract

118 Background: Left-sided RAS/BRAF wild-type metastatic colorectal cancer (mCRC) is sensitive to anti-EGFR containing regimens, however, the impact of clinicopathological features on treatment outcomes in this subgroup remains unclear. This analysis aimed to identify factors associated with EMB-01 response. Methods: In this exploratory baseline characteristics/response subgroup analysis, all patients with left-sided, RAS/BRAF wild-type mCRC and no prior fruquintinib/regorafenib/TAS-102 (favorable group) were selected from a Phase 1/2 study (NCT05176665). Baseline variables—including metastatic status, prior therapies, time from diagnosis, and genomic alterations identified via ctDNA- were collected at screening. Response was assessed by investigators per RECIST v1.1 every 6 weeks. Retrospective correlations between these factors and treatment outcomes were evaluated. Results: As of Jun 9, 2025, 29 response-evaluable mCRC patients with favorable features were included in the analysis. Median prior lines were 3, and ORR was 24.1%. Among them, 22 patients aged <65 years had a higher ORR than older patients (27.3% vs. 14.3%). Patients with single metastatic site (n=7) had slightly higher ORR than those with multiple sites (28.6% vs 22.7%). ORRs were comparable for patients with (n=17) or without (n=12) liver metastases (23.5% vs 25.0%), but modestly higher for those with lung metastases (n=18) than without (27.8% vs 18.2%). No responses occurred among the four patients with peritoneal metastases. Baseline lymph node metastatic patients (n=16) yielded an ORR of 25%. Regarding treatment history, prior anti-EGFR therapy (n=18) was associated with a slightly lower ORR compared to anti-EGFR-naïve patients (22.2% vs 27.3%). Patients diagnosed within 24 months (n=7) or with metastatic disease within 18 months (n=7) had higher ORRs (42.9% and 57.1%, respectively) than their counterparts (18.2% and 13.6%). Patients with ≤2 detected baseline genomic alterations (n=14) showed higher ORR (28.6% vs 20%), DCR (92.9% vs 73.3%) and longer median PFS (24.1 weeks vs 15 weeks). Conclusions: EMB-01 demonstrated a promising efficacy signal in left-sided, RAS/BRAF wild-type mCRC patients naive to 3 rd line SOC. In addition to typical prognostic factors, such as younger age, fewer metastatic sites and shorter intervals from initial or metastatic diagnosis, fewer baseline genomic alterations via ctDNA may be a novel positive indicator for EMB-01 efficacy, while liver/lung metastases appear less impactful as adverse prognostic factors. In summary, these findings warrant further evaluation of EMB-01 in late-line mCRC. Clinical trial information: NCT05176665 .