In a groundbreaking development for pancreatic cancer therapy, the Experimental Drug Development Centre (EDDC) in Singapore has unveiled compelling updates from its ongoing Phase 1 clinical trial involving EBC-129, an innovative antibody-drug conjugate (ADC) designed to target a previously unexploited tumor-specific epitope. This novel therapeutic agent brings hope for patients with pancreatic ductal adenocarcinoma (PDAC), a notoriously aggressive and treatment-resistant malignancy.
EBC-129 represents a first-in-class ADC targeting a unique N256-glycosylated epitope present on two key carcinoembryonic antigen-related cell adhesion molecules, CEACAM5 and CEACAM6. These molecules play significant roles in tumorigenesis, including tumor formation, cellular migration, and metastatic dissemination. By honing in on this specific glycosylation site, EBC-129 promises superior specificity, potentially minimizing off-target effects while maximizing antitumor potency.
The recent Phase 1 trial update was presented at the 2025 Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago, shining a spotlight on the therapeutic potential of EBC-129 among heavily pretreated PDAC patients. The study enrolled 21 participants, all with advanced disease and prior extensive treatment histories, including taxane chemotherapy regimens—a standard yet often insufficient frontline approach. The administration of EBC-129 occurred every three weeks at doses ranging from 1.8 to 2.2 mg/kg, carefully calibrated to optimize therapeutic outcomes.
Crucially, an impressive 82% of enrolled patients harbored tumors expressing the EBC-129 antigen at levels deemed treatable, characterized by at least 1% tumor cell expression at an intensity of 3+ as measured by immunohistochemistry (IHC). This discovery underscores the prevalence of this tumor-specific glycosylated epitope in PDAC, bolstering the rationale for continued clinical exploration of EBC-129 in this patient population.
The efficacy signals derived from the interim analysis are particularly noteworthy. The overall response rates (ORRs) ranged from 20 to 25%, depending on dosing cohorts, accompanied by disease control rates (DCRs) of 63.6% and 87.5% respectively. Additionally, progression-free survival (PFS) was extended to 12 and 19 weeks at the 2.2 mg/kg and 1.8 mg/kg doses, respectively. These metrics are especially encouraging in a refractory setting, where therapeutic gains tend to be incremental at best.
Safety assessments revealed EBC-129 to possess a manageable safety profile. The most common treatment-related adverse events (TRAEs) reported were uncomplicated neutropenia and infusion-related reactions. Such a tolerability spectrum provides a favorable balance between maximizing efficacy and preserving patient quality of life, a crucial consideration in treating late-stage pancreatic cancer.
Beyond pancreatic cancer, exploratory findings suggest that the EBC-129 antigen is broadly expressed across multiple solid tumor types, including gastroesophageal, appendiceal, colorectal, and lung cancers. Tumor sample analyses exhibited moderate to high antigen expression—defined as ≥20% of tumor cells staining at 2+ or 3+ intensity—in 52% to 100% of evaluated specimens. This observation opens intriguing avenues for expanding the clinical applicability of EBC-129 across diverse oncology indications.
From a mechanistic perspective, the payload of EBC-129 is monomethyl auristatin E (MMAE), a potent microtubule-disrupting agent that has seen prior clinical success in other FDA-approved ADCs. MMAE facilitates targeted cytotoxicity, exploiting the selective binding of the antibody component to deliver MMAE directly to cancer cells, thereby limiting systemic toxicity. Moreover, preclinical data suggest synergistic activity when MMAE is combined with immune checkpoint inhibitors such as PD-1 antagonists, a combination currently being evaluated in ongoing arms of the study.
The program’s momentum received a significant boost when the U.S. Food and Drug Administration granted Fast Track Designation for EBC-129 in the treatment of PDAC. This regulatory status underscores the unmet medical need in pancreatic cancer and supports accelerated development by facilitating more frequent interactions with regulatory authorities and eligibility for expedited review pathways.
Expert voices within the oncology community recognize the significance of these early-phase results. Assistant Professor Robert W. Lentz, MD, from the University of Colorado Anschutz School of Medicine, remarked on the therapeutic promise of EBC-129 to address the substantial challenges of metastatic pancreatic adenocarcinoma, particularly in refractory patients resistant to standard-of-care therapies. The convergence of tolerability, disease control, and the observed objective responses fuels cautious optimism for this emerging treatment.
At the helm of the EDDC, Professor Damian O’Connell emphasized the importance of intensified biology-guided clinical trials focusing on EBC-129. He highlighted the agent’s potential not only as a single-agent therapy but also in combination with immunotherapies, envisioning a broader impact on multiple solid tumors harboring the target antigen. The ongoing recruitment for gastroesophageal adenocarcinoma and other IHC-positive tumor cohorts signals the expansive scope of the development program.
Technical advances in immunohistochemistry assays, supporting the precision identification of the tumor-specific glycosylation site, have been vital in refining patient selection and enhancing therapeutic specificity. These innovative diagnostic tools ensure that only antigen-expressing tumors are targeted, enhancing the probability of clinical benefit while mitigating off-target risks.
Collectively, the data emerging from the EBC-129 Phase 1 trial, coupled with robust regulatory support and strategic clinical development, chart a promising path forward in the fight against pancreatic cancer and other challenging solid tumors. If these early trends endure through subsequent trial phases, EBC-129 could herald a new paradigm in glycosylation-targeted oncology therapeutics—ushering in treatments that are as precise as they are potent.
This milestone exemplifies the power of translational science and multidisciplinary collaboration, with the Experimental Drug Development Centre at the forefront of transforming discoveries into potential life-saving medicines. As recruitment expands and additional data accrues, the oncology community keenly awaits further evidence to validate EBC-129’s clinical benefit and safety, potentially offering a pivotal change for patients confronting malignancies with few effective options.
Subject of Research: Antibody-drug conjugates targeting glycosylated epitopes in pancreatic and other solid tumors
Article Title: Emerging Therapeutic Frontiers: EBC-129’s Promise Against Refractory Pancreatic Cancer
News Publication Date: 3 June 2025
Web References: ClinicalTrials.gov, NCT05701527
Keywords: Pancreatic cancer, antibody-drug conjugate, CEACAM5, CEACAM6, glycosylation, EBC-129, monomethyl auristatin E, Phase 1 clinical trial, drug development, oncology, antigen targeting, immunohistochemistry.
