FDA Grants Fast Track Status to EBC-129 for Pancreatic Ductal Adenocarcinoma

The FDA has granted fast track designation to EBC-129 for use as a potential therapeutic option in patients with pancreatic ductal adenocarcinoma.¹

The antibody-drug conjugate (ADC) targets a tumor-specific N256-glycosylation site conserved on CEACAM5 and CEACAM6, which are known to play a key role in tumor formation, migration, and metastasis. The safety and tolerability of the agent as a monotherapy and in combination with pembrolizumab (Keytruda) in patients with advanced solid tumors.²

“The FDA’s fast track designation for EBC-129 underscores the promise of this novel ADC in addressing the critical need for expanded treatment options for patients [with PDAC] and represents an important step in our efforts to accelerate its development,” Professor Damian O'Connell, chief executive officer of the Experimental Drug Development Centre.¹ “We view this as both a validation of our efforts and a responsibility to move decisively to advance EBC-129 as a new option to patients in need.”

The phase 1a dose-escalation study, which leveraged a Bayesian design, enrolled patients with advanced solid tumors who had standard treatment fail; these patients had acceptable organ function and an ECOG performance status of 0 or 1.^3,4 Patients received the ADC at escalating doses of 0.3 mg/kg (n = 1), 0.6 mg/kg (n = 1), 1.2 mg/kg (n = 3), 1.8 mg/kg (n = 5), 2.0 mg/kg (n = 3), and 2.2 mg/kg (n = 5) given every 3 weeks. The primary end point was safety, and secondary end points comprised efficacy and pharmacokinetics.

The median patient age was 72.9 years (range, 53.0-98.3), and most were male (77.8%) and Asian (55.6%). Patients had the following tumor types: PDAC (33%), colorectal cancer (28%), esophageal cancer (22%), gastric cancer (6%), neuroendocrine prostate cancer (6%), and appendiceal cancer (6%). Patients received a median of 3 prior lines of therapy (range, 1-9).

As of the data cutoff date of August 13, 2024, a total of 18 patients received at least 1 dose of the ADC. The maximum tolerated dose was determined to be 2.2 mg/kg. Initial safety data showed that two dose-limiting toxicities were reported at the 2.2-mg/kg dose and the 2-mg/kg dose in the form of grade 4 neutropenia and grade 3 increased aspartate aminotransferase (AST), respectively.

The most common treatment-emergent adverse effects (TEAEs) reported in all patients (n = 18) included chills (72%), pyrexia (67%), decreased neutrophil count (67%), nausea (39%), decreased white blood cell count (33%), fatigue (28%), diarrhea (22%), decreased platelet count (22%), anemia (17%), dyspnea (17%), vomiting (17%), increased AST (17%), myalgia (17%), infusion-related reactions (11%), reduced appetite (11%), upper abdominal pain (11%), increased amylase (11%), dyspepsia (11%), hypokalemia (11%), and hypomagnesemia (11%).

Grade 3 or higher TEAEs included decreased neutrophil count (55%), anemia (11%), decreased white blood cell count (11%), increased AST (6%), diarrhea (6%) vomiting (6%), hypoxia (6%), increased blood bilirubin (6%), dizziness (6%), increased lipase (6%), increased amylase (6%), and febrile neutropenia (6%).

With regard to efficacy, the ADC led to 3 partial responses, which were reported in 2 patients with esophageal adenocarcinomas and 1 patient with PDAC. Eight patients achieved stable disease, and 7 patients experienced disease progression.

Updated data from the study will be shared at the 2025 ASCO Annual Meeting.¹

References

1. Experimental Drug Development Centre granted US FDA fast track designation for antibody-drug conjugate EBC-129 to treat pancreatic ductal adenocarcinoma. News release. Experimental Drug Development Centre. May 28, 2025. Accessed May 28, 2025. https://www.eddc.sg/experimental-drug-development-centre-granted-u-s-fda-fast-track-designation-for-antibody-drug-conjugate-ebc-129-to-treat-pancreatic-ductal-adenocarcinoma/
2. A study of EBC-129 in advanced solid tumors. ClinicalTrials.gov. Updated May 20, 2025. Accessed May 28, 2025. https://clinicaltrials.gov/study/NCT05701527
3. Ng MCH, Yong WP, Meric-Bernstam. A phase I dose escalation study of EBC-129, a first-in-class, anti N-glycosylated CEACAM5 & CEACAM6 antibody-drug conjugate (ADC) in patients with solid tumors. Ann Oncol. 2024;35(suppl 2):S516. doi:10.1016/j.annonc.2024.08.719
4. EBC-129: Phase 1 study of our first-in-class, anti N-glycosylated CEACAM5 & 6 ADC in solid tumours. Experimental Drug Development Centre. October 30, 2024. Accessed May 28, 2025. https://www.eddc.sg/a-phase-1-dose-escalation-study-of-ebc-129-a-first-in-class-anti-n-glycosylated-ceacam5-ceacam6-antibody-drug-conjugate-adc-in-patients-with-solid-tumors/