Sitravatinib Plus Tislelizumab for Patients With Advanced BTC Who Have Failed Prior Treatment

For patients with advanced biliary tract cancer (BTC), the standard of care is immune-checkpoint inhibitor (ICI) in combination with cytotoxic chemotherapy following the TOPAZ-1 and KN-966 studies. However, more research into new drug development with ICI in the second or later lines of treatment is needed.

Research from Jeesun Yoon, MD, and colleagues presented at the 2024 American Society of Clinical Oncology Annual Meeting sought to determine the efficacy of sitravatinib plus tislelizumab as a second-line therapy option for patients with advanced BTC.

In the phase 2, open-label study, patients received sitravatinib 120 mg orally once per day plus tislelizumab 200 mg intravenously once every 3 weeks until reaching disease progression or unacceptable toxicity. The study’s primary end point was disease control rate (DCR), and secondary end points included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety.

For the 43 participants, the median follow-up period was 10.5 months (95% CI, 7.03-15.60). Researchers noted that the study met its primary end point, with a DCR of 65.1% across all populations. In the unselected per-protocol population, ORR was 20.5% and PFS was 4.93 months (95% CI, 3.10-8.87). OS was 10.3 months (95% CI, 6.67-18.20).

Dr. Yoon and colleagues noted that the most reported treatment-related adverse events were sitravatinib related and included hand-foot syndrome and hypertension.

Patients with homologous recombination deficiency (HRD) detected by baseline tissue next-generation sequencing demonstrated increased ORR and improved PFS and OS compared with those without HRD.

“The sitravatinib plus tislelizumab combination as a second-line therapy in patients with advanced BTC demonstrated meaningful efficacy and an acceptable safety profile,” researchers wrote. “Especially, patient selection using HRD biomarker might be a promising strategy in this setting.”