The prognosis of biliary tract cancer (BTC) remains unsatisfactory. This single-arm, phase II clinical trial (ChiCTR2000036652) investigated the efficacy, safety, and predictive biomarkers of sintilimab plus gemcitabine and cisplatin as the first-line treatment for patients with advanced BTCs. The primary endpoint was overall survival (OS). Secondary endpoints included toxicities, progression-free survival (PFS), and objective response rate (ORR); multi-omics biomarkers were assessed as exploratory objective. Thirty patients were enrolled and received treatment, the median OS and PFS were 15.9 months and 5.1 months, the ORR was 36.7%. The most common grade 3 or 4 treatment-related adverse events were thrombocytopenia (33.3%), with no reported deaths nor unexpected safety events. Predefined biomarker analysis indicated that patients with homologous recombination repair pathway gene alterations or loss-of-function mutations in chromatin remodeling genes presented better tumor response and survival outcomes. Furthermore, transcriptome analysis revealed a markedly longer PFS and tumor response were associated with higher expression of a 3-gene effector T cell signature or an 18-gene inflamed T cell signature. Sintilimab plus gemcitabine and cisplatin meets pre-specified endpoints and displays acceptable safety profile, multiomics potential predictive biomarkers are identified and warrant further verification.

Biliary tract tumor is a common malignant disease in clinical practice. Its incidence rate and mortality rate are high, which seriously endangers the health of the people. At present, gastrointestinal surgery is mainly used to treat patients at home and abroad. This paper discusses the main risk factors of biliary tract cancer transformation, analyzes its prognostic characteristics and clinical efficacy, and compares them by comprehensive evaluation methods such as observation group control method, blood routine examination and treatment. The results are as follows: the postoperative adverse reactions in the control group are more obvious than those in the experimental group. There were no obvious clinical manifestations or adverse reactions in the experimental group. The therapeutic effect of biliary tumor transformation can effectively help patients improve their quality of life. Through the prognosis recovery of biliary tract tumor transformation treatment, the health level of patients in the experimental group was higher than that in the control group.

4086 Background: The prognosis of biliary tract cancer (BTC) remains unsatisfactory. Thus, this study aimed to determine the efficacy, safety, and predictive biomarkers of the immune checkpoint inhibitor sintilimab in combination with gemcitabine and cisplatin (GemCis) in advanced BTCs. Methods: In this single-arm, phase II study (Trial registration number: ChiCTR2000036652), gemcitabine (1000 mg/m²) plus cisplatin (25 mg/m²) were administered on days 1 and 8, respectively, while 200 mg sintilimab was administered on day 1 of each 21-day cycle for 6–8 weeks, followed by sintilimab alone up to 2 years. The primary endpoint was overall survival (OS). The second endpoints were objective response rate (ORR), progression-free survival (PFS), and disease control rate, assessed using RECIST V.1.1. Multiomics biomarkers associated with clinical response were assessed as exploratory objectives. Results: Thirty patients were enrolled between August 2020 and May 2022. The median follow-up duration, OS, and PFS were 12.3 months (95% confidence interval [CI]: 9.1–16.0), 15.9 months (95% CI: 8.6–not reached), and 5.1 months (95% CI: 4.3–8.7), respectively. Here, 36.7% of patients were found to achieve an objective response. The most common grade 3 or 4 treatment-related adverse events were thrombocytopenia (33.3%), with no reported deaths nor unexpected safety events. Biomarker analysis indicated that patients with homologous recombination repair pathway gene alterations (median, PFS: 9.8 vs. 4.5 months, p = 0.023; OS: NR vs. 9.0 months, p = 0.014; ORR: 77.8% vs. 19%, p = 0.004) or loss-of-function mutations in chromatin remodeling genes (median, PFS: 8.7 vs. 4.2 months, p = 0.021; ORR: 63.6% vs. 21.1%, p = 0.046) presented better tumor response and survival outcomes. Furthermore, transcriptome analysis of the tumor immune microenvironment revealed a markedly longer PFS, and tumor response were associated with higher expression of 3-gene effector T cell signature (median, PFS: 7.8 vs. 4.3 months, p = 0.02; ORR: 64.2% vs. 7.1%, p = 0.004) and 18-gene inflamed T cell signature (median, PFS: 8.6 vs. 4.3 months, p = 0.01; ORR: 64.2% vs. 7.1%, p = 0.004). Moreover, our findings highlighted the adverse predictive value of mast cells in immuno-chemotherapy for BTCs for the first time. Conclusions: Sintilimab plus GemCis displayed a promising antitumor activity and acceptable safety profile as a first-line treatment in patients with advanced BTC. Multiomics potential predictive biomarkers are identified and warrant further verification. Clinical trial information: ChiCTR2000036652 .

e16189 Background: The overall efficacy of immunotherapy for advanced biliary tract cancers (BTCs) was still poor, exploring the potential biomarkers associated with tumor response in advanced BTCs may further improve the clinical benefits from immunotherapy. Methods: Twelve patients from a phase 2 clinical trial (ChiCTR2000036652), which evaluated the efficacy and safety of sintilimab (anti-PD-1 antibody), plus gemcitabine and cisplatin as first-line treatment in advanced BTC patients, were included in the current biomarkers analysis. Exploratory points mainly focused on differentiated immune-related gene expression and immune pathway signatures using a 289-gene immune-related RNA panel sequencing on baseline tumor samples. Differential gene expression analysis was performed between responders (tumor regression) and non-responders (tumor extension) using Wilcoxon rank-sum test. Signature scores were calculated using the Gene Set Variation Analysis package with publicly available gene signatures. Results: Twelve patients (8 responders vs. 4 non-responders) who had available clinical response evaluations with RNA-sequencing data on baseline tumor samples were included in the current biomarkers analysis. Differential gene expression analysis revealed a significantly increased CXCL10, CXCL13 expression (p < 0.001) and decreased MAGEA12 expression (p < 0.001) in responder tumors compared with non-responder tumors. Differentiated genes were significantly enriched in cytokine-cytokine receptor interaction and interleukin-17 signaling pathway in responder tumors. Extensive analyses on immune pathway signatures showed that higher expression of IFN-γ-related genes (p = 0.048) and T cell-inflamed genes (p = 0.016) were associated with response to immunocombination therapy. Meanwhile, immune cell types score was also calculated, no notable differences were found between defined groups. Conclusions: Some differentially expressed genes were investigated in responder tumors compared with non-responder tumors. Higher expression of IFN-γ-related genes and T cell-inflamed genes could potentially predict the effect of immunocombination therapy. Potential biomarkers are needed to identify patients who respond to sintilimab plus gemcitabine and cisplatin in a larger validation cohort. Clinical trial information: ChiCTR2000036652.