STELLAR: A Phase II, Open-Label, Single-Arm, Prospective Clinical Study of Tislelizumab Combined with Sitravatinib as Consolidation Treatment after Chemoradiotherapy in Locally Advanced, Unresectable Non-Small-Cell Lung Cancer

Abstract

<h3>Purpose/Objective(s)</h3> Consolidation durvalumab has become the standard of care in patients with unresectable, stage III non-small-cell lung cancer (NSCLC) without disease progression after concurrent chemoradiation therapy (cCRT) based on the PACIFIC study. However, there are still about 44% of patients experiencing disease progression or recurrence within one year. New regimens for consolidation treatment are worth exploring to further improve survival for this population. Tislelizumab, an anti-PD-1 antibody engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis (a potential mechanism of resistance), has shown improved efficacy in advanced NSCLC with a tolerable safety profile. Sitravatinib is a spectrum-selective tyrosine kinase inhibitor targeting TAM (Tyro3, Axl, and Mer) and split tyrosine-kinase domain-containing receptors (VEGFR2, KIT), which may potentially augment immune checkpoint blockade through reducing the number of myeloid-derived suppressor cells/regulatory T cells and increasing the ratio of M1/M2 polarized macrophages. An early trial of tislelizumab plus sitravatinib showed acceptable tolerability and promising antitumor activity in advanced NSCLC. STELLAR (NCT05176925) is evaluating tislelizumab plus sitravatinib as consolidation treatment in patients with unresectable, locally advanced, stage III NSCLC after cCRT. <h3>Materials/Methods</h3> This phase II, open-label, single-arm, prospective study is enrolling patients aged from 18-75 years with histologically/cytologically confirmed, locally advanced, unresectable, stage III NSCLC who have not progressed following definitive, platinum-based cCRT, and with ECOG PS of 0 or 1. Patients will be excluded if they have a mixed histological type of small cell lung cancer and NSCLC, or receive prior anti-VEGF mAb, VEGFR TKI or ICI therapy. Patients will receive tislelizumab (200 mg, IV, d1, Q3W) combined with sitravatinib (starting dose 70 mg, po, qd; escalating to 100 mg, qd, after 2 cycles) for up to 1 year until disease progression, intolerable toxicity, withdrawal of consent or death. The primary endpoint is 1-year progression-free survival (PFS) rate by investigator assessment per RECIST v1.1. Secondary end points are PFS, objective response rate, duration of response and disease control rate assessed by investigators per RECIST 1.1, overall survival, time to distant metastasis, and safety. AEs will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0. Enrollment begins in January 2022, and approximately 36 patients will be enrolled. <h3>Results</h3> N/A <h3>Conclusion</h3> N/A