Phase III study of tislelizumab (TIS) with sitravatinib versus chemotherapy (chemo) in patients with locally advanced/ metastatic non-small cell lung cancer (NSCLC) previously treated with chemo and an anti-programmed cell death protein 1/ligand 1 (PD-[L]1) antibody

Most patients (pts) with advanced NSCLC do not respond to PD-(L)1inhibitor monotherapy. Sitravatinib is an oral spectrum-selective tyrosine kinase inhibitor, which can reduce the number of myeloid-derived suppressor cells and regulatory T cells, and increase the ratio of M1/M2 polarized macrophages, promoting an antitumor microenvironment. TIS is an anti-PD-1 antibody engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a potential mechanism of resistance to PD-1 therapy. In a Phase 1 study (NCT03666143), sitravatinib plus TIS demonstrated clinical efficacy and had a manageable safety profile. This is a Phase 3, global, randomized, open-label study (NCT04921358) designed to evaluate the efficacy and safety of sitravatinib plus TIS vs chemo, for the treatment of pts with locally advanced or metastatic NSCLC. A total of 420 pts will be randomized (1:1) to take TIS 200 mg intravenously (IV) once every three weeks (Q3W) plus sitravatinib 100 mg orally once a day, or docetaxel monotherapy 75 mg/m2 IV Q3W, until disease progression, intolerable toxicity, or death. Adult pts with disease progression on or after ≤ 2 lines of prior systemic chemo and PD-(L)1 therapy with an ECOG performance status of ≤ 1 and ≥ 1 measurable lesion are eligible. Stratification factors are histology (squamous vs non-squamous), PD-L1 expression (< 1% tumor cell [TC] vs ≥ 1% TC assessed by the VENTANA SP263 assay), and race (Asian vs non-Asian). Co-primary endpoints are overall survival and independent review committee (IRC) assessed progression-free survival (PFS [RECIST v1.1]) in the intent-to-treat population. Secondary endpoints include investigator-assessed (INV) PFS, IRC-assessed objective response rate (ORR), duration of response (DoR), disease control rate (DCR), quality of life, safety, and pharmacokinetics (PK) of sitravatinib. Exploratory endpoints include INV-assessed ORR, DoR, DCR, PK of the active metabolite of sitravatinib, predictive and prognostic value of PD-L1 expression, and biomarker analysis. NCT04921358. This study was sponsored by BeiGene, Ltd. Medical writing support, under the direction of the authors, was provided by Victoria Dagwell, MSc, and Louise Oakes, PhD, of Ashfield MedComms, an Ashfield Health company, and was funded by BeiGene, Ltd. BeiGene, Ltd. BeiGene, Ltd.