Updated results of anlotinib plus benmelstobart combined with nab-paclitaxel and cisplatin as first-line treatment for advanced biliary tract cancer: A single-arm, open-label phase II clinical trial.

e16224 Background: Efficacy and prognosis of chemotherapy in first-line setting for patients with advanced biliary tract cancer (BTC) was dismal currently. Recently, PD-1/PD-L1 blockades combined with dual chemotherapy in first-line setting exhibited superior efficacy for patients with BTC. Nevertheless, it's important to highlight that both the TOPAZ-1 and KEYNOTE-966 trials had reported a median OS of less than 13 months. This underscored the necessity for further advancements to meet the demands of clinical practice. Anlotinib, a novel multitarget TKI primarily targeting VEGFR1-3, demonstrated promising therapeutic activity as second-line therapy for patients with BTC. Therefore, this study was designed to explore the efficacy and safety of anlotinib plus benmelstobart combined with nab-paclitaxel and cisplatin as first-line therapy in advanced BTC. Preliminary results were presented at the 2024 ASCO-GI Symposium (Abs 498), the 2024 ASCO (e16144) , the consecutively updated results were presented in this report. Methods: Patients with previously untreated metastatic or locally advanced BTC were recruited and treated with anlotinib (10mg, po, d1~14, q3w) and benmelstobart (1200mg, iv, d1, q3w) plus nab-paclitaxel (200mg/m 2 , iv, d1, q3w) and cisplatin (60mg/m 2 , iv, d1, q3w) until disease progression or unacceptable toxicity. Primary endpoint was ORR and secondary endpoints included safety, DCR, PFS, OS and biomarker investigation. Results: From April 2023 to Oct 2023, a total of 20 patients were enrolled. At the data cut-off date (Nov, 2024), the best overall response indicated that there were 12 PR (60.0%), 6 SD (30.0%) and 2 PD (10.0%). Therefore, the preliminary ORR was 60.0% (95%CI: 36.1%-80.9%), DCR was 90.0% (95%CI: 68.3%-98.8%). At the data cut-off date, the preliminary prognostic result exhibited that the median PFS of the 20 pts was 10.05 months (95%CI: 5.65-12.32), the median OS was 20.14 months (95%CI: 10.45-NE) . Additionally, safety profile exhibited that the regimen was tolerable. The most common TEAEs > 30% were leukopenia (80%), peripheral sensory neuropathy (45%) and fever (35%). Grade ≥3 TEAEs were leukopenia (30%), fever (5%), decreased platelet count (5%), malaise (5%), nausea (5%), stomachache (5%), oral mucositis (5%), vomit (5%), rash (5%) and hypotension (5%). Conclusions: Preliminary results suggested that anlotinib plus benmelstobart combined with nab-paclitaxel and cisplatin as first-line therapy in advanced BTC exhibited encouraging efficacy and manageable adverse events. The conclusion should be validated in more patients subsequently. Clinical trial information: NCT05812430 .