Tiragolumab Plus Atezolizumab and Chemotherapy in Extensive-Stage Small Cell Lung Cancer

Clinical Summary:

• Design/Population: The phase 3 SKYSCRAPER-02C trial evaluated tiragolumab plus atezolizumab and chemotherapy in treatment-naïve patients with extensive-stage small cell lung cancer.
• Key Outcomes: Tiragolumab did not significantly improve overall survival and progression-free survival compared to placebo, despite numerical improvements. Biomarker analyses identified immune-inflamed molecular subtypes associated with greater benefit.
• Clinical Relevance: Tiragolumab added to atezolizumab plus chemotherapy did not establish a clear survival benefit in unselected ES-SCLC, but exploratory biomarker findings suggest potential activity in PD-L1–positive and immune-inflamed subgroups, supporting further biomarker-directed evaluation of anti-TIGIT strategies.

Results from the phase 3 SKYSCRAPER-02C trial demonstrated that the addition of tiragolumab to atezolizumab plus chemotherapy did not significantly improve survival among patients with extensive-stage small cell lung cancer (ES-SCLC). 

“Despite the improved outcomes achieved with immunotherapy-based regimens, most patients with ES-SCLC experience disease progression and a significant unmet need remains for novel therapeutic strategies to improve long-term survival and symptom control,” stated Shun Lu, MD, PhD, Shanghai Jiao Tong University School of Medicine, Shanghai, China, and coauthors. “Tiragolumab may synergize with other immunotherapies to enhance antitumor immune responses.”

In this  double-blind, placebo-controlled trial, 123 patients were randomized 1:1 to receive either 600 mg of tiragolumab (n = 61) or placebo (n = 62) plus 1200 mg of atezolizumab and 4 cycles of carboplatin plus etoposide, followed by maintenance tiragolumab or placebo plus atezolizumab once every 3 weeks until disease progression, loss of clinical benefit, or unacceptable toxicity. Primary end points included progression-free survival (PFS), overall survival (OS), and confirmed objective response rate (ORR) in patients without baseline brain metastases (tiragolumab n = 54; placebo n = 56). Key secondary end points included PFS, OS, and confirmed ORR, regardless of baseline brain metastases. 

At a median follow-up of 26.7 months, median PFS was 5.6 months in the tiragolumab arm and 5.4 months in the placebo arm with estimated 12-month PFS rates of 27.7% and 10.2%, respectively. Median OS was 18.7 months in the tiragolumab arm and 13.5 months in the placebo arm with estimated 12-month OS rates of 50.7% and 49.3%, respectively. Investigator-assessed confirmed ORR was 81.5% in the tiragolumab arm and 58.9% in the placebo arm. In the full analysis set, median PFS was consistent with the primary analysis set. Median OS was 17.3 months in the tiragolumab arm and 14.9 months in the placebo arm, and invesitgator-assessed confirmed ORR was 77% and 59.7%, respectively. 

Any-grade adverse events were reported in 100% of patients in the tiragolumab arm and 98.4% of patients in the control arm, with Grade 3/4 adverse events occurring  in 88.3% and 82.5% of patients, respectively. Treatment-related adverse events were reported in 100% of patients in the tiragolumab arm and 95.2% of patients in the placebo arm, and most frequently included anemia, neutrophil count decrease, white blood cell count decrease, and platelet count decrease. Grade 3/4 treatment-related adverse events were reported in 85% and 79.4% of patients, respectively. Adverse events led to 5 treatment discontinuations and 3 deaths, including 2 which were deemed treatment related. 

Exploratory biomarker analyses suggested that patients with PD-L1-positive tumors and immune-inflamed molecular subtypes NMF3 and NMF4 may derive greater benefit from tiragolumab. Tumors characterized by high T-effector and tumor-associated macrophage immune signatures also appeared more likely to benefit from tiragolumab-based therapy.

“While results from the global SKYSCRAPER-02 study were not statistically significant, numerical improvements in PFS and OS were seen with tiragolumab plus atezolizumab [and chemotherapy],” concluded Dr Lu et al. “These findings provide insights for future investigations of the anti-TIGIT class of drugs and checkpoint inhibitors in the treatment of ES-SCLC.”

Source:

Lu S, Fang J, Yu Y, et al. SKYSCRAPER-02C: A Phase 3, randomized, double-blind, placebo-controlled study of atezolizumab plus carboplatin and etoposide with or without tiragolumab in patients with untreated extensive-stage small cell lung cancer in China. J Thorac Oncol. Published online: April 5, 2026. doi:10.1016/j.jtho.2026.103713