Among patients locally advanced, unresectable, stage 3 non-small cell long cancer (NSCLC) that has not progressed after platinum-based concurrent chemoradiation (cCRT), consolidation therapy with tiragolumab plus Tecentriq (atezolizumab) did not improve independent review facility (IRF)-assessed progression-free survival (PFS) versus standard Imfinzi (durvalumab) therapy, study results have shown.
Findings from the phase 3 SKYSCRAPER-03 trial were presented at the 2025 ESMO Congress.
At a median follow-up of 30.7 months, the median IRF-PFS in the overall population was 14.2 months in patients receiving the combination versus 13.8 months in patients treated with Imfinzi. The 24-month PFS event-free rates were 39% and 38.5%, respectively. The median overall survival (OS) was 45.6 months versus 45.8 months, respectively. The 24-month OS event-free rates were 67% versus 66.3%, respectively.
The primary end point was also missed in PD-L1–positive patients with a median IRF-PFS of 19.4 months versus 16.6 months in patients treated with the combination versus Imfinzi, respectively. The median OS in these patients was not estimable versus 54.8 months, respectively. The 24-month PFS and OS event-free survival rates were 46.1% versus 42.9% and 72.2% versus 69.2%, respectively.
“SKYSCRAPER-03 did not meet its primary end point of IRF-PFS. There were no new or unexpected [safety] findings,” said first study author Dr. Rafal Dziadziuszko, department of oncology and radiotherapy of the Medical University of Gdansk, Poland.
What Was the Safety Profile of the Combination and Monotherapy Arms in the Trial?
“Tiragolumab plus [Tecentriq] demonstrated a tolerable safety profile, consistent with previous observations for the combination,” said Dziadziuszko.
Grade 3 (severe)/4 (life-threatening) treatment-related side effects occurred in 13.8% of patients in the combination arm, with serious treatment-related side effects experienced by 11.5%. There were two patient deaths considered to be related to the combination treatment. In the Imfinzi arm, grade 3/4 treatment-related side effects and serious treatment-related side effects each occurred in 10.7% of patients. There were seven patient deaths considered to be related to Imfinzi treatment.
What Was the Study Rationale and Design for the Trial?
Regarding the rationale for the study, Dziadziuszko explained, “Consolidation [Imfinzi] is the standard of care for patients with unresectable, stage 3 NSCLC that has not progressed following cCRT; however, disease recurrence [still] represents an unmet need.”
He added that the immune checkpoint target TIGIT has a role in cancer immune evasion and the study hypothesis was that tiragolumab, an anti-TIGIT monoclonal antibody, could potentially augment antitumor activity when used in combination with immunotherapies such as Tecentriq.
The open-label phase 3 trial was launched to test this hypothesis in patients with newly diagnosed, unresectable, stage 3 NSCLC whose disease has not progressed following at least two cycles of definitive platinum-based cCRT. Patients had to have known PD-L1 status and an ECOG performance status of 0 or 1. Patients with EGFR- or ALK-positive tumors were not eligible for enrollment.
At 1 to 42 days post cCRT, patients were randomized to combination therapy with tiragolumab (840 mg IV every four weeks) plus Tecentriq (1680 mg IV every four weeks) or single-agent Imfinzi (10 mg/kg IV every two weeks or 1500 mg IV every four weeks). Patient could receive up to 13 cycles of treatment (28-day cycles).
What Were the Patient Characteristics in the Trial?
Patient characteristics were well balanced between the two study arms. The median age was 64 years in the combination arm versus 65 years in the Imfinzi arm. About half of patients in each arm were aged less than 65 years at 50.8% and 47.4%, respectively. About 80% of patients in each arm were male, about 60% were White and about 35% were Asian. Patients’ ECOG performance status was mostly split evenly between 0 and 1, with a slightly higher number of patients in each arm at ECOG 1 status. About 75% of patients in each arm were former tobacco users and about 20% were current tobacco users.
Reference
- “SKYSCRAPER-03: Phase III, open-label, randomised study of atezolizumab (atezo) + tiragolumab (tira) vs durvalumab (durva) in locally advanced, unresectable, stage III non-small cell lung cancer (NSCLC) after platinum-based concurrent chemoradiation (cCRT),” Dr. Rafal Dziadziuszko et al, presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA69.
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