Sitravatinib plus tislelizumab demonstrated clinical benefit in patients with advanced biliary tract cancer who have presence of HRD
Medical News
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2024-07-24
In the phase 2 study of sitravatinib combination with tislelizumab, DCR was 69.2% in ITT population after median follow-up of 10.5 months. Patients with homologous recombination repair deficiency (HRD) had better survival outcome comparing with HRP. This result was presented in 2024 ASCO annual meeting.
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In advance biliary tract cancer, ICI combined chemotherapy has been the standard of care for first-line therapy. Even though, there is still huge unmet need in second-line treatment after exposure of ICI. Except for the FGFR2 fusion and IDH1 mutation, chemotherapy is still the second-line standard of care in advance BTC. Sitravatinib is a multi-kinase inhibitor targeting TAM family receptors (TYRO3, AXL, MERTK) and split kinase family receptors (VEGF-R2, MET, RET, and KIT). Tislelizumab is a humanized monoclonal antibody directed against PD-1.
According to the study design of phase 2 trial of combination of sitravatinib and tislelizumab, disease control rate is primary endpoint. After 10.5 months of median follow-up, DCR (by per-protocol) were 69.2%, 65.5% and 85.7% in total population, ICI-naïve and ICI-treated, respectively. PFS and OS were 4.93 months and 10.3 months in overall population.
Additionally, HRD (homologous recombination repair deficiency) status was analyzed in biomarkers analysis data. HRDness is defined by deletion, frameshift, nonsense, and multiple missense mutation of ATM, ATR, BAP1, BARD1, BRCA1, BRCA2, BRIP1, CDK12, CHEK1, CHEK2, FANCL, MRE11, NBN, PALB2, RAD51, RAD51B, RAD51C, RAD51D, RAD54L, XRCC2 genes. PFS and OS in HRD patients were better than HRP patients (PFS: not reach vs 4.87 m, p=0.018; OS: 21.13 m vs 8.57, p=0.098).
Above all, combination of sitravatinib and tislelizumab has showed clinical benefit as the second-line treatment in advance BTC, and presence of HRD might be a potential biomarker for optimal patient selection.
Reference: Jeesun Yoon et al., Phase II study of sitravatinib in combination with tislelizumab in patients with advanced biliary tract cancer who have failed to at least 1 prior systemic treatment. JCO 42, 4018-4018(2024).