Preliminary results from a first-in-human study of ESG401, a trophoblast cell-surface antigen 2 (TROP2) antibody drug conjugate (ADC), in patients with locally advanced/metastatic solid tumors.

Abstract

1100 Background: ESG401 is an innovative ADC composed of a humanized anti-TROP2 IgG1 monoclonal antibody conjugated to topoisomerase I inhibitor SN-38 via a proprietary stable-cleavable linker with DAR of 8. Methods: Patients (pts) aged ≥18 years with locally advanced/metastatic solid tumors refractory to/relapsed from standard treatment with measurable disease (RECIST v1.1) were eligible. ESG401 is administered intravenously by designated dose and regimen until unacceptable toxicity or progressive disease. The Bayesian Optimal Interval (BOIN) design was used to establish the MTD. Results: As of Feb 3, 2023, 35 pts with a median age of 53 were treated with ≥1 dose of ESG401 during escalation at doses of 2-20 mg/kg once Q3W (Regimen A), or 12-16 mg/kg D1,8,15 in a 4-week cycle (Regimen B). 80% of pts were ECOG = 1, 63% of pts were 3L+; median 4 (2-10) prior lines, 94% of pts had visceral metas (11% brain, 63% liver, 60% lung) at baseline. Only one patient treated with 20 mg/kg experienced DLT. The MTD has not reached either regimen. The most common TRAEs were leukopenia (80%), neutropenia (69%), anemia (66%), fatigue (54%), nausea (51%), and vomiting (46%). The most common ≥ Grade 3 TRAEs were leukopenia (29%) and neutropenia (31%). There was no ≥ Grade 3 thrombocytopenia, diarrhea, skin rash, or oral mucositis. No Interstitial Lung Disease (ILD) was observed. Of 33 efficacy evaluable (EE) pts, 12 partial responses (PR) were observed and 4 pts had achieved SD ≥24 wks. The first dose level found PR (16 mg/kg Q3W) and afterward were taken as therapeutically relevant doses (TRD). The ORR and DCR were 36% (4/11) and 64% (7/11) in 11 TRD pts with TNBC, while 62% (8/13) and 77% (10/13) in 13 TRD pts with HR+/HER2-BC. Two pts with brain metas both got an obvious intracranial response (one pt whose intracranial lesion was significantly reduced to too small to measure). Until the cut-off date, 11 (31%) pts remained on treatment. Three pts were treated over 12 mons and the longest on-treatment duration was 12.9 mons. One pt had consistent PR up to 10.8 mons. Conclusions: The preliminary data demonstrated that ESG401 is safe and well-tolerated with promising signals of efficacy in heavily pretreated pts. These encouraging findings warrant further clinical evaluation. Clinical trial information: NCT04892342 . [Table: see text]