Tiragolumab/Atezolizumab for NSCLC Fails to Meet End Points in SKYSCRAPER-06
The SKYSCRAPER-06 trial for the first-line treatment of non–small cell lung cancer was stopped because the combination of tiragolumab and atezolizumab did not improve survival compared with the control of pembrolizumab and chemotherapy.
The phase 2/3 SKYCRAPER-06 study (NCT04619797) of the investigational anti-TIGIT antibody tiragolumab for the first-line treatment of non–small cell lung cancer (NSCLC) will not continue.1
The agent, in combination with the PD-L1 inhibitor atezolizumab (Tecentriq), did not significantly improve survival compared with the control of pembrolizumab (Keytruda) and chemotherapy.
“These results are disappointing as it was our hope that this combination might yield improved outcomes for people living with metastatic nonsquamous lung cancer,” said Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche, said in a press release. “We are thankful to all of the patients and health care professionals involved in the study, and we will leverage the learnings to inform our scientific understanding of the anti-TIGIT pathway and new avenues in cancer research.”
At the primary analysis, the tiragolumab/atezolizumab combination missed its primary end point of progression-free survival (PFS; HR, 1.27; 95% CI, 1.02-1.57). At the first interim analysis, overall survival (OS) data was immature but also inferior to the active comparator arm (HR, 1.33; 95% CI, 1.02-1.73).
The study enrolled 542 patients with nonsquamous NSCLC that was locally advanced or metastatic and previously untreated. Based on these results, the study will be unblinded.
The safety profile of tiragolumab plus atezolizumab is consistent with what has been previously observed, and no new safety signals were identified.
About the SKYSCRAPER Studies
Additional SKYSCRAPER studies are investigating the combination of tiragolumab and atezolizumab across tumor types, with several focusing on lung cancer.
The phase 3 SKYSCRAPER-01 study (NCT04294810) is looking at the combination vs placebo and atezolizumab in patients with previously untreated, locally advanced unresectable or metastatic, PD-L1-selected NSCLC. In August 2023, Roche announced that the combination led to a median OS of 22.9 months vs 16.7 months in the comparator arm (HR, 0.81); however, this did not meet statistical significance.2
SKYSCRAPER-02 (NCT04256421) is a phase 3 study evaluating atezolizumab plus carboplatin and etoposide with or without tiragolumab in patients with untreated extensive-stage small cell lung cancer (SCLC). Findings were published in the Journal of Clinical Oncology and showed that while the combination was well-tolerated, adding tiragolumab did not add additional benefit to atezolizumab, carboplatin, and etoposide. The median OS was 13.1 months in both arms (stratified HR, 1.14; P =.2859).3
SKYSCRAPER-03 (NCT04513925) is looking at the atezolizumab/tiragolumab combination compared with durvalumab (Imfinzi) in patients with locally advanced, unresectable stage III NSCLC. Patients in this study have received at least 2 cycles of concurrent platinum-based chemotherapy and do not have radiographic disease progression. A total of 829 patients are enrolled.4
SKYSCRAPER-15 (NCT06267001), which is currently recruiting, is investigating tiragolumab/atezolizumab vs placebo/atezolizumab in patients with completely resected NSCLC who have received adjuvant platinum-based chemotherapy. Centers in 11 states and 10 additional countries are enrolling patients.5
