As reported in JAMA Oncology by Socinski et al, the phase III SKYSCRAPER-06 trial showed no progression-free or overall survival benefit with tiragolumab, a monoclonal antibody targeting T-cell immunoreceptor with Ig and ITIM domains (immunoreceptor tyrosine-based inhibitory motifs) (TIGIT), plus the PD-L1 inhibitor, atezolizumab, and chemotherapy vs placebo plus pembrolizumab, a PD-1 inhibitor, and chemotherapy in patients with advanced nonsquamous non–small cell lung cancer (NSCLC).
Study Details
In the global double-blind trial, 542 patients were randomly assigned between December 2020 and September 2023 to receive tiragolumab at 600 mg, atezolizumab at 1,200 mg, and chemotherapy with pemetrexed at 500 mg/m2 and carboplatin AUC = 5 or cisplatin at 75 mg/m2 (n = 269) or placebo, pembrolizumab at 200 mg, and the same chemotherapy (n = 273) on day 1 of 21-day cycles until progression, loss of clinical benefit, or unacceptable toxicity. The primary endpoints were investigator-assessed progression-free survival and overall survival.
Key Findings
Median investigator-assessed progression-free survival was 8.3 months (95% confidence interval [CI] = 7.1–9.6 months) in the tiragolumab plus atezolizumab group vs 9.9 months (95% CI = 8.7–11.9 months) in the placebo plus pembrolizumab group (hazard ratio [HR] = 1.27, 95% CI = 1.02–1.57, P = .99). Median overall survival was 18.9 months (95% CI = 15.2–23.8 months) in the tiragolumab plus atezolizumab group vs 23.1 months (95% CI = 20.7–33.0 months) in the placebo plus pembrolizumab group (HR = 1.33, 95% CI = 1.02–1.73, P = .98).
Grade 3 to 4 adverse events occurred in 61.4% of the tiragolumab plus atezolizumab group vs 60.7% of the placebo plus pembrolizumab group, most commonly anemia (23.2% vs 22.1%) and decreased neutrophil count (10.1% vs 9.9%) in both groups. Death considered related to treatment occurred in 3.4% vs 2.6% of patients. Immune-mediated adverse events of any grade occurred in 70.0% vs 62.5% of patients, most commonly rash (40.1% vs 26.5%) and hepatitis (29.2% vs 29.4%) in both groups.
The investigators concluded: “In the phase 3 SKYSCRAPER-06 randomized clinical trial, the primary end points were not met and the study has been terminated.”
Mark A. Socinski, MD, of Thoracic Oncology Program, AdventHealth Cancer Institute, Orlando, Florida, is the corresponding author for the JAMA Oncology article.
DISCLOSURE: The study was funded by F. Hoffmann–La Roche/Genentech. For full disclosures of the study authors, visit jamanetwork.com.
