Preliminary safety and efficacy of SYS6010 combined with enlonstobart in patients with recurrent or metastatic esophageal cancer: Results from a phase I/II study.

e16052 Background: SYS6010 is a novel antibody-drug conjugate (ADC), consisting of an anti-epidermal growth factor receptor (EGFR) humanized IgG1 monoclonal antibody linked to topoisomerase I inhibitor (JS-1). Enlonstobart is a fully humanized anti-PD-1 IgG4 monoclonal antibody. In most recurrent or metastatic (R/M) esophageal cancer (EC) and selected advanced solid tumors, PD-1 based chemo-immunotherapy is standard treatment yet limited by resistance. Mechanistically, certain EGFR-targeted ADCs can complement PD-1 immunotherapy and hold promise for enhancing anti-tumor activity. This phase I/II study (ChiCTR2400089402) is to evaluate the safety, tolerability, pharmacokinetic profile and preliminary efficacy of SYS6010 combined with Enlonstobart ± chemotherapy in patients with EGFR and ALK wild type locally advanced or metastatic non-small cell lung cancer and other advanced solid tumors. Here, we present the preliminary safety and efficacy results of SYS6010 combined with Enlonstobart in patients with R/M EC from the phase II portion. Methods: In the phase II EC cohort, eligible patients were those aged 18 to 75 years with R/M EC who had not received prior systemic therapy, or who had received adjuvant/neoadjuvant therapy with disease progression occurring at least 6 months after completion of treatment. Patients received SYS6010 at 3.6 mg/kg and Enlonstobart at 240 mg every 2 weeks (Q2W). Primary endpoints were safety, tolerability and objective response rate (ORR) assessed by investigators. Results: As of January 05, 2026 (data cut-off), 32 patients were enrolled. The median age was 63 years (range, 36-72) and 81.3% of patients were male. The median treatment exposure was 19.64 weeks (IQR, 12.43-25.86). 96.9% of patients experienced at least one treatment-emergent adverse event (TEAE). The incidence of grade ≥3 TEAEs was 31.3%. The most common grade ≥3 TEAEs were neutropenia (12.5%), leukopenia (6.3%) and anemia (6.3%). One patient experienced death, which was assessed as unrelated to treatment. No patients discontinued treatment due to TEAEs. 29 patients were evaluable for efficacy, with confirmed ORR and disease control rate of 65.5% (95% CI, 45.7-82.1) and 93.1% (95% CI, 77.2-99.2), respectively. The 6-month progression-free survival (PFS) rate was 68.2% (95% CI, 40.6-85.0). The confirmed 3-month duration of response (DOR) rate was 91.7% (95% CI, 53.9-98.8). Median PFS, median DOR and overall survival were not yet mature. Conclusions: This study demonstrates that the combination therapy of SYS6010 and Enlonstobart has the potential to represent a novel and effective treatment option for patients with R/M EC. The promising clinical activity, together with a manageable safety profile, supports further clinical development of this regimen. Clinical trial information: ChiCTR2400089402.