SKYSCRAPER-03: A Phase III, Open-Label, Randomized Study of Atezolizumab Plus Tiragolumab Compared With Durvalumab in Patients With Locally Advanced, Unresectable, Stage III NSCLC Who Have Not Progressed After Platinum-Based Concurrent Chemoradiation.

Abstract

PURPOSE/OBJECTIVE(S): Until recently, the standard of care for patients (pts) with locally advanced, unresectable, stage III non-small cell lung cancer (NSCLC) has been platinum-based concurrent chemoradiation (cCRT); however, the 5-year OS rates are poor (13-36%; Goldstraw et al. J Thorac Oncol 2015). Durvalumab (anti-PD-L1) monotherapy was recently approved for pts without progressive disease (PD) after cCRT. However, long-term OS data are not yet available and further evaluation of novel cancer immunotherapy combinations should be explored. Targeted inhibition of a novel checkpoint TIGIT/PVR, by the anti-TIGIT antibody tiragolumab, may amplify the anti-cancer activity of anti-PD-L1/PD-1 antibodies. In the phase II CITYSCAPE study (NCT03563716), tiragolumab plus atezolizumab (anti-PD-L1) was well tolerated and improved ORR compared with atezolizumab alone (31.3 vs 16.2%) in 1L pts with PD-L1+ (TPS =1%) metastatic NSCLC; with greater benefit in the PD-L1-high (TPS =50%) subset. We hypothesize that tiragolumab plus atezolizumab may provide greater clinical benefit vs single-agent anti-PD-L1 as maintenance therapy in pts with unresectable, stage III NSCLC who have not progressed after platinum-based cCRT. SKYSCRAPER-03 (NCT04513925) will determine if tiragolumab plus atezolizumab provides superior clinical benefit to durvalumab in this setting. Current data suggests that cCRT upregulates PD-L1 expression, potentially enabling PD-L1 low or negative tumors to derive benefit, so outcomes will be evaluated in all-comer (ITT) and PD-L1+ sub-populations.MATERIALS/METHODS: Eligible pts (=18 years) must have unresectable, stage III NSCLC without PD after =2 cycles of platinum-based cCRT per NCCN/ESMO guidelines, and without an EGFR mutation or ALK rearrangement; known PD-L1 status; ECOG PS 0-1. Approximately 800 pts will be randomized 1:1 to receive tiragolumab 840mg IV plus atezolizumab 1680mg IV Q4W or durvalumab 10mg/kg IV Q2W / 1500mg IV Q4W. Treatment will continue for up to 13 cycles of 28 days, or until unacceptable toxicity or symptomatic deterioration due to PD; in pts with radiographic PD (per RECIST v1.1) treatment may continue if evidence of ongoing clinical benefit. Stratification factors include PD-L1 status, histology (squamous vs non-squamous), staging (IIIA vs IIIB or IIIC) and ECOG PS (0 vs 1). Primary endpoint is independent review facility-assessed PFS in the ITT and PD-L1+ (TC =1%) populations. Secondary endpoints include investigator-assessed PFS, OS, ORR and DoR. Safety and biomarker analyses will be performed. Recruitment is ongoing.RESULTS: forthcoming CONCLUSION: forthcoming.

View details for DOI 10.1016/j.ijrobp.2021.07.1203

View details for PubMedID 34701413