CEA-High Expression Shows Early Promise as a Biomarker for BG-C477 in NSCLC

In a phase 1a dose-escalation and safety-expansion study of the antibody drug conjugate (ADC) BG-C477 (NCT06596473), the confirmed objective response rate was 60.0% (95% CI, 38.7-78.9) among patients with CEA-high non–small cell lung cancer (NSCLC), defined as immunohistochemistry (IHC) 2+ or 3+ in at least 50% of tumor cells, compared with 37.2% (95% CI, 23.0%-53.3%) in the overall NSCLC population.¹

Matthew Lee, MD, an assistant professor of medical oncology at City of Hope in Duarte, California, who presented these findings at the 2026 European Society for Medical Oncology (ESMO) Congress, spoke with CancerNetwork^® about how confident he is that CEA, also known as CEACAM5, will hold up as a clinically actionable biomarker for patient selection, and what validating that biomarker would require. Despite the preliminary nature of the data, Lee said that the CEA-high patient subgroup represents the “most promising group” to assess with the agent.

Transcript:

CancerNetwork: The CEA-high subgroup showed a higher ORR vs the CEA-low group. How confident are you that CEA/CEACAM5 expression will hold up as a clinically actionable biomarker for patient selection, and what would validation of that biomarker require?

Lee: This is a first-in-human, phase 1 type of trial, so the numbers presented right now are very preliminary, but they do show a promising signal. From the early numbers we’re seeing, the CEA-high group, which is IHC 2 to 3-plus in greater than 50% of tumor cells, shows a differential response compared with the [lower-expressing group].

Initially, the phase 1 design actually used a serum CEA cutoff of greater than 5 ng/mL, and then we retrospectively looked at CEA IHC and saw a differential response. We’re also interested in whether serum CEA correlates with CEA IHC, and that’s one of the key things we’ll [look at] as we gather more information in the dose-expansion phase and get larger numbers to see whether this pans out. At this moment, with the preliminary data we have, I’d say the CEA IHC 2 to 3-plus group is probably the most promising group to look at for now, but it will be interesting to see whether we can also incorporate serum CEA in the future, which could further expand how many patients might benefit from this [CEACAM5-targeted] ADC.

Reference

Lee M, Gong Y, Fu S, et al. BG-C477, a CEA (CEACAM5)-targeting antibody-drug conjugate, in patients with advanced non-small cell lung cancer: results from a phase 1a dose-escalation and safety-expansion study. Presented at: European Society for Medical Oncology (ESMO) Congress 2026; October 23-27, 2026; Madrid, Spain. Abstract 2567P.