Becotatug Vedotin Plus Anti-PD-1 and S-1 in Patients With EGFR-Positive Advanced Pancreatic Cancer Who Have Failed at Least One Line of Standard Therapy

This is a prospective, single-arm, single-center exploratory clinical study. The purpose of this study is to evaluate the efficacy and safety of a triplet regimen-becotatug vedotin combined with anti-PD-1 and S-1-in patients with EGFR-positive advanced pancreatic cancer who have failed at least one line of standard systemic therapy. Pancreatic cancer is one of the most lethal malignancies, and patients who progress after first-line treatment have very limited effective options. The study plans to enroll 27 participants aged 18 years or older with histopathologically confirmed pancreatic cancer, evidence of recurrence or metastasis (or disease not amenable to complete surgical resection), EGFR positivity confirmed by immunohistochemistry, an ECOG performance status of 0 to 3, and at least one measurable target lesion. All participants will receive becotatug vedotin 2.0 mg/kg intravenously on Day 1 every three weeks, anti-PD-1 200 mg intravenously on Day 1 every three weeks, and oral S-1 40 to 60 mg twice daily on Days 1 to 14 followed by a 7-day rest, repeated every three weeks. Treatment will continue until disease progression, unacceptable toxicity, completion of 12 months of treatment, or other protocol-defined discontinuation criteria. Tumor response will be assessed by CT or MRI every 9 weeks according to RECIST v1.1, and safety will be assessed according to NCI-CTCAE version 5.0. The primary endpoint is objective response rate (ORR). Secondary endpoints include disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. The study duration is approximately 3 years, with participant enrollment planned from OCT. 2026 to OCT. 2027. All participants will receive active treatment; no placebo is included. This study addresses a major unmet medical need, as current second-line and later treatment options for advanced pancreatic cancer provide only limited benefit.