First results of an open-label, single arm phase II trial investigating the efficacy and safety of trifluridine/tipiracil combined with irinotecan as a second line therapy in patients with cholangiocarcinoma.

4121 Background: Cholangiocarcinoma (CCA) is a rare and aggressive malignancy with poor prognosis. Although firstline therapy with gemcitabine, cisplatin and durvalumab has been established based on the TOPAZ-1 trial, treatment options for subsequnt therapies remain limited. The TRITICC study investigated the combination of trifluridine/tipiracil (FTD/TPI) and irinotecan in patients with disease progression after firstline treatment. Methods: TRITICC was a phase IIA, interventional, prospective, open-label, non-randomized, exploratory, multicenter, single-arm trial. Adult patients with histologically confirmed, locally advanced or metastatic biliary tract cancer received FTD/TPI (25 mg/m² BSA, BID, orally, days 1–5 of each 14-day cycle) combined with irinotecan (180 mg/m² on day 1 of each cycle). Progression free survival (PFS) was the primary endpoint. Secondary endpoints included the PFS rate at 4 months, median overall survival (OS), objective response rate (ORR), and quality of life. The trial was registered with ClinicalTrials.gov (NCT04059562) and EudraCT (2018-002936-26). Results: 28 patients were enrolled across six sites in Germany. The median PFS was 3.1 months (95% CI: 2.0–7.5), with PFS rates of 35% (95% CI: 21%–58%) at 4 months, 30% (95% CI: 17%–54%) at 6 months, and 13% (95% CI: 4.7%–37%) at 12 months. PFS and PFS rates were higher in patients with intrahepatic CCA (iCCA). The OS rates were 74% (95% CI: 59%–93%) at 6 months and 38% (95% CI: 22%–68%) at 12 months. Similar to the PFS rates the OS rates were higher in iCCA. Among 27 evaluable patients, partial responses were observed in 3 patients (11.1%, 2 iCCA, 1 eCCA), stable disease in 11 patients (40.7%, 7 iCCA, 4 eCCA). Thirteen patients (48.1%, 7 iCCA, 6 eCCA) experienced disease progression. Outcomes due to tumor location will have to be examined in higher patient numbers. The most frequently reported adverse events included neutropenia, thrombocytopenia, gastrointestinal symptoms and fatigue. The mean Global Health Status score (EORTC QLQ-C30) declined moderately from 56.2 at screening to 46.4 at the end of treatment. No severe, unmanageable or unexpected toxicities were reported. Conclusions: The combination of FTD/TPI and irinotecan demonstrated promising efficacy and manageable safety in CCA patients progressing after first-line gemcitabine-based therapy, aligning with recent findings in comparable populations (e.g., Tella et al.). Further investigations are warranted to validate these results. The NIFTY trial suggested that pegylated irinotecan may enhance efficacy compared to conventional irinotecan, a hypothesis that will be explored in the planned follow-up TRITICC-2 study. The study was funded by Servier Deutschland GmbH and Servier Affaires Médicale. Clinical trial information: NCT04059562 .