retlirafusp alfa + indole-3-carbinol + black garlic fermentation extract + Lactobacillus rhamnosus + paclitaxel + cisplatin + PD-1 inhibitor

This experimental combination regimen is a biomarker-guided precision treatment strategy being evaluated for the first-line treatment of advanced metastatic esophageal squamous cell carcinoma (ESCC). The regimen consists of a backbone of TP chemotherapy (paclitaxel and cisplatin) and a PD-1 inhibitor, supplemented by additional agents based on patient biomarker profiles: retlirafusp alfa (a bifunctional PD-L1/TGF-βRII fusion protein) for TGF-β positive patients; indole-3-carbinol and black garlic fermentation extract for metabolite-guided intervention; or Lactobacillus rhamnosus for microbiome-guided intervention. This multi-modal approach aims to enhance anti-tumor immunity by simultaneously targeting immune checkpoints, the TGF-β signaling pathway, and the gut-microbiome-tumor axis.