SKYSCRAPER-05: A Phase 2 Study of Perioperative Tiragolumab Plus Atezolizumab, With or Without Platinum-Based Chemotherapy, in Patients With Previously Untreated, Locally Advanced, Resectable, Stage II‒IIIB NSCLC.

Introduction: The SKYSCRAPER-05 (NCT04832854), a phase 2, open-label, multicenter study, evaluated perioperative treatment with tiragolumab plus atezolizumab ± platinum-based chemotherapy in treatment-naive patients with resectable, stage II-IIIB NSCLC. Methods: Cohort A (programmed death ligand-1 [PD-L1]-high) received 4 cycles of neoadjuvant tiragolumab (600 mg IV) plus atezolizumab (1200 mg IV) every 3 weeks, surgery, and the investigator's choice of adjuvant tiragolumab plus atezolizumab (16 cycles) or platinum-based chemotherapy (4 cycles). Cohort B (PD-L1 all-comers) received tiragolumab plus atezolizumab plus platinum-based chemotherapy (4 cycles), surgery, and tiragolumab plus atezolizumab every 3 weeks (16 cycles). The co-primary end points were major pathologic response (MPR), surgical feasibility, and safety; the secondary end points were pathologic complete response and event-free survival. Results: At clinical cutoff (February 14, 2024), 50 patients were enrolled (70% male; 66% White), and 48 received treatment (Cohort A, n = 7; Cohort B, n = 41; median follow-up, 9.5 months); 96% of whom underwent resection (4% pneumonectomy, 91% lobectomy or bilobectomy; 93% R0). Cohort A was halted early because of changing treatment paradigms. Cohort B MPR was 51% (95% confidence interval: 35-67) and pathologic complete response was 29% (95% confidence interval: 17-46). Event-free survival was immature. At safety cutoff (March 05, 2025), grade 3 or higher treatment-related adverse events (AEs) occurred in 29% and 44% of patients in Cohorts A and B, respectively; surgery-related grade 3 or higher AEs occurred in 14% and 5%. AEs led to surgical delays in 2 patients and treatment discontinuation in 14 patients (34.1%, all in Cohort B). Conclusions: Perioperative tiragolumab combined with atezolizumab ± chemotherapy proved to be surgically feasible, with acceptable MPR rates and a safety profile aligned with expectations for resectable, locally advanced NSCLC.