EBC-129 Shows Early Activity in Advanced Pancreatic Ductal Adenocarcinoma

No grade 5 events observed in the study, no ocular events reported, neuropathy was seen in only 6% of patients, and no patients discontinued treatment due to toxicity.

EBC-129 showed encouraging early antitumor actiivity in patients with heavily pretreated advanced pancreatic ductal adenocarcinoma (PDAC), with a 20% objective response rate (ORR), 71.4% disease control rate (DCR), and median progression-free survival (PFS) of 12.9 weeks, according to early results from a phase 1 trial (NCT05701527) presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.1

Among 21 enrolled patients, most had received at least 3 prior lines of therapy (47.6%), and over 80% had previously received taxanes. Twenty patients with PDAC were evaluable for response. At the 1.8 mg/kg dose, the ORR was 25%, and median PFS reached 19.1 weeks. At the 2.2 mg/kg dose, ORR was 20.0% and the median PFS was 12.1 weeks. Overall, including the 2 mg/kg dose, the ORR was 20.0%, and the median PFS was 12.9 weeks.

“EBC-129 monotherapy is active in heavily pretreated metastatic [patients with] PDAC, and has a manageable safety profile,” said Robert W. Lentz, MD, assistant professor in the Division of Medical Oncology in the Department of Medicine at University of Colorado Anschutz School of Medicine, during his presentation of the data at ASCO 2025.

About EBC-129

EBC-129 is a first-in-class antibody-drug conjugate (ADC) that targets N256-glycosylated CEACAM5 and CEACAM6, 2 antigens that are highly prevalent in PDAC and associated with aggressive tumor biology. EBC-129 uses a fully humanized monoclonal antibody linked to monomethyl auristatin E (MMAE) via a cleavable linker, with a drug-to-antibody ratio of 4. The molecule also has inherent antibody-dependent cellular cytotoxicity activity.

The preclinical rationale for dual targeting of CEACAM5 and 6 rests in their roles in cell migration and invasion and their collective overexpression in gastrointestinal tumors.

Behind the Phase 1 Study in PDAC

The study enrolled patients aged 18 years and older in the US and 21 years and older in Singapore who had measurable disease by RECIST v1.1 on imaging, an ECOG performance status of 0 or 1, and histologically or cytologically confirmed unresectable locally advanced or metastatic solid tumors. Patients had confirmed CEACAM5/6 expression on archival tissue and included those with either ≥20% of cells staining at 2+/3+ intensity or ≥1% at 3+ intensity by immunohistochemistry (IHC). No clear correlation was seen between expression levels and response.

Patients in the study received EBC-129 every 3 weeks at doses of 1.8, 2.0, or 2.2 mg/kg, with 1.8 and 2.2 mg/kg established as recommended phase 2 doses. The median age of the 21 patients included was 63.0 years (range, 44.0-81.0), 52% of patients were male, and 11 patients were Asian while 10 patients were White. Seventeen patients (81.0%) received prior taxanes. Five patients were stage I at diagnosis, 3 were stage II, 3 were stage III, 8 were stage IV, and 2 were unknown.

“Among the 4 partial responses, 1 was confirmed, 3 were unconfirmed due to subsequent progression, and 3 of these patients had prior taxane exposure,” said Lentz. “Three patients experienced stable disease for longer than 6 months, with a disease control rate of 71.4% in the entire group. There was no apparent correlation between IHC score and treatment response, including in 1 partial responder with 1% of cells at 3+ expression. Three patients continue on the trial.”

Safety Results and Biomarker Analysis

EBC-129 was generally well tolerated, with a safety profile consistent with MMAE-based ADCs. Overall, the most common treatment-related adverse events (TRAEs) were infusion-related reactions (13.8%), predominantly grade 1 or 2 and effectively mitigated with premedication, and neutropenia, which was seen in 31.0% of patients. Neutropenia was typically manageable with growth factor support.

There were no grade 5 events observed in the study and no ocular events reported. Neuropathy was infrequent, seen in only 6% of patients, and no patients discontinued treatment due to toxicity.

“EBC-129 has a manageable safety profile with neutropenia and infusion-related reactions as the primary treatment-related adverse events,” added Lentz.

Biomarker analysis revealed that most patients had higher baseline serum levels of CEACAM6 than CEACAM5 (18/21; 86%), consistent with prior observations in PDAC biology.

Future Directions

“The EBC-129 antigen (N256-glycosylated CEACAM5/6) has a high prevalence of IHC positivity in patients with metastatic pancreatic adenocarcinoma,” said Lentz.

Given these results, EBC-129 has received FDA fast track designation for PDAC. A phase 2 trial is planned to launch in 2026 through the Academic GI Cancer Consortium.2

The study will explore EBC-129 both as monotherapy and in combination with gemcitabine in second-line metastatic PDAC. If confirmed in later-phase trials, EBC-129 could represent a novel treatment option for a patient population with few effective therapies and a historically poor prognosis.

References

1. Lentz RW, Ng MC, Yong WP, et al. Clinical activity of EBC-129, a first-in class, anti N256-glycosylated CEACAM5 and CEACAM6 antibody-drug conjugate (ADC), in patients with pancreatic ductal adenocarcinoma (PDAC) in a phase 1 study. J Clin Oncol. 2025;43 (suppl 17):4018. doi:10.1200/JCO.2025.43.16_suppl.4018
2. Experimental Drug Development Centre granted U.S. FDA fast track designation for antibody-drug conjugate EBC-129 to treat pancreatic ductal adenocarcinoma. News release. The Experimental Drug Development Centre. May 28, 2025. Accessed June 2, 2025. https://tinyurl.com/yv3rtm3w