Cecilia Brown

Lung Cancers Today

The<a href="https://www.lungcancerstoday.com/post/officials-provide-update-on-phase-3-skyscraper-01-study" target="_blank" rel="noopener"> phase 3 SKYSCRAPER-01</a> 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&ndash;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&ndash;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 &ldquo;has shown encouraging survival outcomes&rdquo; in patients with metastatic NSCLC, with these results &ldquo;primarily&rdquo; 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.&ldquo;Today, checkpoint inhibitors are the frontline standard treatment for these patients with non&ndash;small cell lung cancer, which cannot be radically treatable [when] locally advanced or metastatic without actionable genomic alterations,&rdquo; Dr. Peters said. &ldquo;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.&rdquo;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 &ldquo;balanced between treatment arms,&rdquo; 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 &ldquo;demonstrated an acceptable safety profile, consistent with previous observations,&rdquo; according to Dr. Peters and colleagues.Although the primary end points were not met in the SKYSCRAPER-01 study, the study authors explained that &ldquo;numerical improvements in both PFS and OS&rdquo; with the combination treatment &ldquo;suggest potential antitumor activity of TIGIT targeting in NSCLC.&rdquo;&ldquo;It might be that TIGIT blocking is not sufficient to completely restore the immune activation of both T cells and NK [natural killer] cells,&rdquo; Dr. Peters said during the AACR session. &ldquo;However, tiragolumab may augment the antitumor activity and responses.&rdquo;Source:American Association for Cancer Research 2025. Abstract #CT051. <a href="https://www.abstractsonline.com/pp8/#!/20273/presentation/10424" target="_blank" rel="noopener">https://www.abstractsonline.com/pp8/#!/20273/presentation/10424</a>

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The phase 3 SKYSCRAPER-01 study did not meet its primary end points of overall survival (OS) and investigator-assessed progression-free survival, according to AACR 2025 data.