Phase 3 SKYSCRAPER-01 Study: Final PFS, OS Analyses Presented at AACR 2025

The phase 3 SKYSCRAPER-01 study did not meet its primary end points of overall survival (OS) and investigator-assessed progression-free survival (PFS) in patients with previously untreated PD-L1-high, locally advanced unresectable or metastatic non–small cell lung cancer (NSCLC), according to a presentation at the American Association for Cancer Research (AACR) Annual Meeting 2025.

Solange Peters, MD, PhD, of the Centre Hospitalier Universitaire Vaudois Oncology Department, presented results from the double-blind, placebo-controlled, randomized trial during the Therapeutic Advances in Non–Small Cell Lung Cancer session at the AACR Annual Meeting.

The phase 3 trial is evaluating the efficacy and safety of first-line tiragolumab, an anti-TIGIT monoclonal antibody, plus atezolizumab in patients with previously untreated, PD-L1-high NSCLC. Dr. Peters and colleagues explained that the combination of tiragolumab plus atezolizumab “has shown encouraging survival outcomes” in patients with metastatic NSCLC, with these results “primarily” observed in patients with PD-L1-high tumors, defined as having a tumor proportion score of at least 50%.

During the AACR Annual Meeting session, Dr. Peters spoke about why it was critical to evaluate the combination treatment strategy in this population of patients.

“Today, checkpoint inhibitors are the frontline standard treatment for these patients with non–small cell lung cancer, which cannot be radically treatable [when] locally advanced or metastatic without actionable genomic alterations,” Dr. Peters said. “However, the vast majority of our patients, probably more than 85% of them, eventually experience this progression, indicating a very high remaining unmet need for new treatment options in this patient category.”

The study included patents with previously untreated PD-L1-high, locally advanced unresectable or metastatic NSCLC who had wild-type EGFR and ALK. Study investigators randomized 534 patients 1:1 to receive IV tiragolumab 600 mg plus IV atezolizumab 1200 mg (n=266) or placebo plus IV atezolizumab 1200 mg (n=268) every 3 weeks until disease progression, loss of clinical benefit, or unacceptable toxicity occurred. Patient characteristics were “balanced between treatment arms,” Dr. Peters and colleagues explained.

The primary end points of the study were investigator-assessed PFS and OS in the primary analysis set. Secondary end points included the investigator-assessed objective response rate and investigator-assessed duration of response in the primary analysis set.

At the final PFS analysis, which had a median follow-up of 9.9 months, the study showed that the median investigator-assessed PFS was 7 months in patients receiving the combination treatment, compared with 5.6 months in those receiving placebo plus atezolizumab (hazard ratio [HR], 0.78; 95% CI. 0.63-0.97; P=0.02). At the final OS analysis, which had a median follow-up of 17.9 months, the median OS was 23.1 months with tiragolumab plus atezolizumab, compared with 16.9 months with placebo plus atezolizumab (HR, 0.87; 95% CI, 0.71-1.08; P=0.22).

However, tiragolumab plus atezolizumab “demonstrated an acceptable safety profile, consistent with previous observations,” according to Dr. Peters and colleagues.

Although the primary end points were not met in the SKYSCRAPER-01 study, the study authors explained that “numerical improvements in both PFS and OS” with the combination treatment “suggest potential antitumor activity of TIGIT targeting in NSCLC.”

“It might be that TIGIT blocking is not sufficient to completely restore the immune activation of both T cells and NK [natural killer] cells,” Dr. Peters said during the AACR session. “However, tiragolumab may augment the antitumor activity and responses.”

Source:

American Association for Cancer Research 2025. Abstract #CT051. https://www.abstractsonline.com/pp8/#!/20273/presentation/10424