Clinical outcomes in phase 1 study of EBC-129, a first-in-class, anti–N256-glycosylated CEACAM5 and CEACAM6 antibody-drug conjugate (ADC), in patients with gastroesophageal adenocarcinomas.

Abstract

3033 Background: Gastro-oesophageal adenocarcinoma (GEA) is an aggressive malignancy with limited treatment options. EBC-129 is a first in class MMAE-linked ADC against both, N256-glycosylated CEACAM5 and 6. Previously reported dose escalation data identified 1.8 and 2.2 mg/kg Q3W as the RP2Ds. Here we report pooled safety and efficacy data of GEA patients enrolled in dose escalation (DEs) and expansion (DEx) cohorts of the Phase 1 study (NCT05701527). Methods: This study consisted of DEs and DEx cohorts. Previously treated patients with histologically confirmed, locally advanced or metastatic GEA with centrally confirmed immunohistochemistry (IHC) positivity at ≥20% at 2 + and/or 3 + on archival samples were enrolled. Objectives were to evaluate safety, efficacy, PK of EBC-129, administered every 3 weeks. Results: A total of 21 GEA patients were enrolled (4 in DEs and 17 in DEx). Pre-screening data shows that 57% and 77% are positive in IHC at cut-offs of ≥20% at 2/3 + and ≥1% at 3 + , respectively. Patients received 1.2 (n=1), 1.8 (n=9), 2.0 (n=1) or 2.2 (n=10) mg/kg EBC-129 Q3W. 81% were male; mean age 59.0 years; median 3 (range 1-9) lines of previous treatments with 62% prior taxane treated. At data cut-off (9 th Jan 2026), 3 patients are continuing treatment, 12 patients had radiological progression, 3 had clinical progression, and 3 patients withdrew from treatment. Among the 17 evaluable patients, the ORR, DCR and median PFS are outlined in the table below. ORR of 50% was seen in patients with an IHC ≥50%. 65% of patients had any tumour shrinkage overall. Infusion related reactions (IRRs) were seen in 43% of patients most being Grade 1/2 and resolved or reduced with premedication; except for 1 patient who had Grade 3 IRR. The other ≥3 Grade TRAEs (CTCAE v5) included neutropenia (52.4%), anaemia (14.3%), WBC count decreased (9.5%), diarrhoea (9.5%); and amylase increase, vomiting, anorexia, nausea in 1 patient each (4.8%). 4 patients (19.0%) experienced peripheral neuropathy (3 grade 1, 1 grade 2). Other than the 1 patient with Grade 3 IRR, no other drug-related discontinuations occurred in this cohort. Higher antigen expression levels correlated with better response. Conclusions: EBC-129 shows promising clinical activity in heavily treated GEA patients with a manageable tolerability profile. Further evaluation in 2L GEA is planned. Clinical trial information: NCT05701527 . Efficacy results from EBC-129-01, GEA cohort. Dose IHC status * ORR^ DCR mPFS (wks) 1.8 mg/kg ≥20% (n=7) 28.5% 85.7% 18.1 1.8 mg/kg ≥50% (n=4) 50% 100% 29.2 2.2 mg/kg ≥20% (n=8) 25.0% 75.0% 10.1 2.2 mg/kg ≥50% (n=5) 40% 80% 9.3 Overall (All doses) ≥20% (n=17) # 29.4% 82.4% 17.86 Overall (All doses) ≥50% (n=10) # 50% 90% 21.4 *Centrally confirmed IHC positivity at 2 + and/or 3 + on archival samples were enrolled; ^Includes one patient with unconfirmed response; #1 patient each at 1.2 mg/kg and 2.0 mg/kg.