SKYSCRAPER-01: Tiragolumab in Combination With Atezolizumab in Previously Untreated PD-L1–High, Locally Advanced, Unresectable or Metastatic Non–Small Cell Lung Cancer

Author(s): Solange Peters, MD, PhD¹; Roy Herbst, MD, PhD²; Hidehito Horinouchi, MD, PhD³; Luis Paz-Ares, MD, PhD⁴; Melissa Johnson, MD⁵; Benjamin J. Solomon, MBBS, PhD⁶; Mahmut Gumus, MD⁷; Mustafa Erman, MD⁸; Igor Bondarenko, MD, PhD⁹; Dong-Wan Kim, MD, PhD¹⁰; Enriqueta Felip, MD, PhD¹¹; Alessandro Morabito, MD¹²; Maciej Bryl, MD, PhD¹³; Laszlo Urban, PhD^14,15; Kaname Nosaki, MD¹⁶; Martin Reck, MD, PhD¹⁷; Raymond Meng, MD, PhD¹⁸; Chipman Stroud, PharmD¹⁸; Palak Kundu, MD¹⁸; Xiaohui Wen, MD¹⁸; Namrata S. Patil, PhD¹⁸; Meilin Huang, PhD¹⁸; Sarah Troutman, PharmD¹⁸; Christina Matheny, PhD¹⁸; Byoung Chul Cho, MD, PhD¹⁹;

Source: DOI: 10.1200/JCO-25-02777

Dr. Anjan Patel's Thoughts

This is another nail in the anti-TIGIT coffin. In more than 500 patients with untreated PD-L1–high non–small cell lung cancer (NSCLC), adding tiragolumab to atezolizumab missed both primary endpoints, and the numerical progression-free survival (PFS) and overall survival (OS) gains never reached significance. What it did add was toxicity: twice the grade 3–4 adverse events (AEs) and more discontinuations. Together with the other failed TIGIT programs, this pretty much closes the door on chemo-free anti-TIGIT combinations in first-line NSCLC, so single-agent PD-(L)1 or chemo-IO stays the standard for these patients.

PURPOSE

Tiragolumab plus atezolizumab has shown encouraging survival outcomes in metastatic non–small cell lung cancer (NSCLC), primarily in patients with PD-L1–high tumors. We further evaluated the combination of tiragolumab plus atezolizumab in the phase III SKYSCRAPER-01 study.

METHODS

Patients with untreated, locally advanced unresectable/metastatic PD-L1–high (by central laboratory testing) NSCLC were randomly assigned 1:1 to receive either tiragolumab (600 mg) plus atezolizumab (1,200 mg) or placebo plus atezolizumab (1,200 mg) intravenously in 21-day cycles until disease progression, loss of clinical benefit, or unacceptable toxicity. Primary end points were investigator-assessed progression-free survival (INV-PFS) and overall survival (OS) in the primary analysis set (PD-L1–high per 22C3 assay).

RESULTS

Five hundred twenty-one patients were randomly assigned to either the tiragolumab plus atezolizumab group (n = 262) or the placebo plus atezolizumab group (n = 259). the primary PFS analysis (Mar 12, 2022; median follow-up 9.9 months [IQR, 6.2-13.8]), median INV-PFS was 7.0 months (95% CI, 5.6 to 9.8) with tiragolumab plus atezolizumab and 5.6 months (95% CI, 4.4 to 7.0) with placebo plus atezolizumab (hazard ratio [HR], 0.78 [95% CI, 0.63 to 0.97]; P = .02 [nonsignificant]). the final OS analysis (Sept 24, 2024; median follow-up 17.9 months [IQR, 6.7-39.0]), median OS was 23.1 months (95% CI, 17.7 to 28.8) with tiragolumab plus atezolizumab and 16.9 months (95% CI, 14.6 to 21.3) with placebo plus atezolizumab (HR, 0.87 [95% CI, 0.7 to 1.1]; P = .22 [nonsignificant]). Overall, 41.2% (n = 110/267) and 33.8% (n = 89/263) of patients experienced grade 3-4 adverse events with tiragolumab plus atezolizumab and placebo plus atezolizumab, respectively. Four and two treatment-related deaths occurred in each group, respectively.

CONCLUSION

Tiragolumab plus atezolizumab did not demonstrate a statistically significant INV-PFS or OS benefit over atezolizumab in patients with previously untreated PD-L1–high NSCLC.

Author Affiliations

¹Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland; ²Yale School of Medicine and Yale Cancer Center, New Haven, CT; ³National Cancer Center Hospital, Tokyo, Japan; ⁴Hospital Universitario 12 de Octubre, Madrid, Spain; ⁵Sarah Cannon Research Institute, Nashville, TN; ⁶Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; ⁷Istanbul Medeniyet University, Istanbul, Türkiye; ⁸Hacettepe University Cancer Institute, Ankara, Türkiye; ⁹Dniprovsky State Medical University, Dnipro, Ukraine; ¹⁰Seoul National University College of Medicine and Seoul National University Hospital, Seoul, Republic of Korea; ¹¹Vall d’Hebron University Hospital, Barcelona, Spain; ¹²Instituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy; ¹³E.J. Zeyland Wielkopolska Center of Pulmonology and Thoracic Surgery, Poznan, Poland; ¹⁴Matrahaza University and Teaching Hospital, Heves, Hungary; ¹⁵St. Lazarus County Hospital, Salgótarján, Hungary; ¹⁶National Cancer Center Hospital East, Kashiwa, Japan; ¹⁷Airway Research Center North, German Center for Lung Research, Lung Clinic Grosshansdorf, Grosshansdorf, Germany; ¹⁸Genentech, Inc, South San Francisco, CA; ¹⁹Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea

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