A Phase 2 Clinical Trial of Anlotinib Plus TQB2450 (PD-L1 Blockade) Plus Nab-Paclitaxel and Cisplatin as First-Line Treatment for Advanced BTC

The efficacy of first-line chemotherapy for patients with biliary tract cancer (BTC) is poor and is associated with a poor prognosis. The combination of dual chemotherapy and programmed death-ligand 1 (PD-L1) blockade in patients with BTC has demonstrated remarkable effectiveness in first-line treatment.^1,2

Despite the findings from the TOPAZ-1 and KEYNOTE-966 trials, which revealed a median overall survival (OS) of <13 months, further advancements are necessary in this clinical setting.^3,4

In a phase 2 study, anlotinib, a novel multitarget tyrosine kinase inhibitor primarily targeting vascular endothelial growth factor 1-3, demonstrated promising efficacy as second-line therapy for patients with BTC.⁵

A phase 2 study at ASCO GI explored the safety and efficacy of anlotinib plus TQB2450 (PD-L1 blockade) combined with nab-paclitaxel and cisplatin as first-line therapy in advanced BTC.

Patients were included if they had histologically confirmed metastatic or locally advanced BTC, no prior systemic therapy for BTC, were aged 18 to 75 years, and had a life expectancy of ≥12 weeks. They had an Eastern Cooperative Oncology Group performance status of 0 or 1.

The primary endpoints were overall response rate (ORR), and secondary endpoints included safety, disease control rate (DCR), progression-free survival (PFS), OS, and exploration of biomarkers.

Patients were treated for 6 cycles with orally administered anlotinib (10 mg on days 1-14; once every 3 weeks [Q3W]), intravenously (IV) administered TQB2450 (1200 mg on day 1; Q3W), IV-administered nab-paclitaxel (200 mg/m² on day 1; Q3W), and IV-administered cisplatin (60 mg/m² on day 1; Q3W) until disease progression or unacceptable toxicity.

Analysis of the best ORR indicated that 6 (42.9%) patients had a partial response, 7 (50.0%) patients had stable disease, and 1 (7.1%) patient had progressive disease.

From April 2023 to August 2023, 18 patients were enrolled. However, 14 patients who received their first tumor response were included in the analysis. Enrolled patients had a median age of 57.5 years.

Analysis of the best ORR indicated that 6 (42.9%) patients had a partial response, 7 (50.0%) patients had stable disease, and 1 (7.1%) patient had progressive disease.

The preliminary ORR was 42.8%, and the DCR was 92.9%. Median PFS was not reached.

The most common treatment-emergent adverse events (TEAEs) among the 18 enrolled patients included leukopenia (67%), fever (39%), pain in extremities (33%), and malaise (28%). The most common grade ≥3 TEAEs were leukopenia (28%), fever (6%), malaise (6%), stomachache (6%), oral mucositis (6%), thrombocytopenia (6%), vomit (6%), rash (6%), and hypotension (6%).

These preliminary results suggest that anlotinib plus TQB2450, nab-paclitaxel, and cisplatin as first-line therapy in patients with advanced BTC showed encouraging efficacy with a manageable safety profile. However, these conclusions should be validated in more patients in future studies.⁶

References

1. Yan X, Zou H, Lai Y, et al. Efficacy and safety of first-line targeted treatment and immunotherapy for patients with biliary tract cancer: a systematic review and meta-analysis. Cancers (Basel). 2022;15(1).
2. Jiang Q, Huang J, Zhang B, et al. Efficacy and safety of anti-PD1/PDL1 in advanced biliary tract cancer: a systematic review and meta-analysis. Front Immunol. 2022;13:801909.
3. Oh D-Y, He AR, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evidence. 2022;1(8):EVIDoa2200015.
4. Kelley RK, Ueno M, Yoo C, et al. Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023;401(10391):1853-1865.
5. Jin S, Zhao R, Zhou C, et al. Updated results from the phase II study: efficacy and safety of anlotinib plus sintilimab as second-line treatment for patients with advanced biliary tract cancers. J Clin Oncol. 2023;41(suppl 4):577.
6. Jin SL, Qiao SS, Li RF, et al. Anlotinib plus TQB2450 (PD-L1 blockade) combined with nab-paclitaxel and cisplatin as first-line treatment for advanced biliary tract cancer: a single-arm, open label phase II clinical trial. San Francisco, CA, & online: presented at ASCO Gastrointestinal Cancers Symposium; January 18-20, 2024: poster D5.