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

Gastrointestinal Cancer |
Image credit: © Sebastian Kaulitzki
– stock.adobe.com

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/