Perioperative tiragolumab combined with atezolizumab (Tecentriq) plus or minus chemotherapy proved to be surgically feasible in patients with locally advanced resectable non–small cell lung cancer (NSCLC) with a safety profile that aligned with expectations, according to data from the phase 2 SKYSCRAPER-05 study (NCT04832854) presented during the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer.1

Of the total 50 patients included in the trial, 48 underwent surgery. The most common procedure was lobectomy (85%), followed by bilobectomy (7%), right or left pneumonectomy, segmentectomy, or other (2% each). Most patients achieved R0 (93%), and 7% had classification of R1. Of the 8 total patients in cohort A with PD-L1–high disease, 7 underwent surgery, all in the form of lobectomy. Most patients achieved R0 (86%) and 14% had a classification of R1. Moreover, of the 42 total patients in cohort B with any PD-L1 expression, 41 underwent surgery. The most common procedure was lobectomy (82%), followed by bilobectomy (8%), right or left pneumonectomy, segmentectomy, or other (3% each). Ninety-five percent of patients achieved R0, and 5% had a classification of R1.

At a median follow-up of 9.5 months, and when broken down by PD-L1 expression, those in cohort A who had high expression experienced a major pathological response (MPR) rate of 71% (95% CI, 30.3%-94.9%) and a pathologic complete response (pCR) rate of 29% (95% CI, 5.1%-69.7%). In those with any PD-L1 expression in cohort B, the MPR and pCR rates were 51% (95% CI, 35.4%-66.9%) and 29% (95% CI, 16.7%-45.7%), respectively. In those with PD-L1 expression below 1% (n = 23), those with expression ranging from 1% to 49% (n = 10), and those with a PD-L1 expression of 50% or higher (n = 8), the MPR rates were 43% (95% CI, 23.9%-65.1%), 60% (95% CI, 27.4%-86.4%), and 63% (95% CI, 25.9%-89.8%), respectively; the pCRs in the respective groups were 22% (95% CI, 8.3%-44.2%), 20% (95% CI, 3.5%-55.8%), and 63% (95% CI, 25.9%-89.8%).

The 12-month event-free survival (EFS) rate in cohort A was 100% and 76% in cohort B; the respective 24-month rates were 86% and 60%.

“The SKYSCRAPER-05 study confirmed surgical feasibility after neoadjuvant treatment with tiragolumab plus atezolizumab, with or without platinum-based chemotherapy, for patients with locally advanced resectable NSCLC,” Catherine A. Shu, MD, of NYU Langone Health, Grossman School of Medicine, and New York University, in New York, NY, said in a presentation of the data. “MPR and pCR rates seen across PD-L1 subgroups with perioperative tiragolumab plus atezolizumab were similar to other perioperative immunotherapy plus chemotherapy regimen.”

What Is the Study Design of the SKYSCRAPER-05 Trial?

The open-label, multicenter, phase 2 study enrolled patients with resectable stage II, IIIA, or select IIIB (T3N2) NSCLC who did not have prior exposure to immunotherapy, chemotherapy, or radiotherapy for lung cancer but had an ECOG performance status of 0 or 1.1,2 Patients were required to have tissue evaluable to determine PD-L1 status.

Those in cohort A received 600 mg of intravenous (IV) tiragolumab every 3 weeks (Q3W) plus 1200 mg of IV atezolizumab Q3W for 4 cycles followed by surgery and MPR/pCR assessment.1 After surgery, they received both drugs at the same doses Q3W for 16 cycles or platinum-based chemotherapy Q3W for 4 cycles. Those in cohort B received 600 mg of tiragolumab Q3W plus 1200 mg of atezolizumab Q3W plus platinum-based chemotherapy Q3W for 4 cycles followed by surgery and response assessment. They then went on to receive tiragolumab and atezolizumab at the same doses Q3W for 16 cycles. Notably, post-operative radiotherapy was optional for R1 or R2 resection and/or ypN2 at the time of resection.

Primary end points included safety of neoadjuvant and adjuvant tiragolumab plus atezolizumab—specifically adverse effects (AEs) as well as surgical feasibility and outcomes—and efficacy of neoadjuvant treatment in the form of MPR per local pathology. Secondary end points included efficacy of neoadjuvant treatment in the form of pCR per local pathology and efficacy of neoadjuvant and adjuvant treatment in the form of investigator-assessed EFS.

What Should Be Known About the Patients Enrolled to SKYSCRAPER-05?

Of the 50 total patients included, 66% were 65 years or older. Most patients were male (70%) and White (66%). Regarding histology, 54% had squamous disease and 46% had nonsquamous disease. Regarding disease stage, 40% had stage II disease, 24% had stage IIIA N2+ disease, 30% had stage IIIA N2- disease, and 6% had stage IIIB disease. In terms of PD-L1 expression, 48% had tumor cell expression below 1%, 20% had expression between 1% and 49%, and 32% had expression of 50% or higher.

In cohort A, 7 of the 8 patients received at least 1 dose in the neoadjuvant phase; 5 of them completed treatment, and 2 discontinued. All 7 underwent surgery and response assessment. In the adjuvant phase, 3 completed plus atezolizumab and 2 completed chemotherapy only; 2 discontinued or never started treatment in this phase. The most common reason for treatment discontinuation was physician's decision (29%), followed by disease progression (14%).

In cohort B, 41 of 42 patients received at least 1 dose in the neoadjuvant phase; 38 completed treatment, and 3 discontinued. A total of 39 patients underwent surgery and response assessment. In the adjuvant phase, 15 patients completed treatment with tiragolumab and atezolizumab, and 24 discontinued or never began treatment in this phase. The most common reason for treatment discontinuation was adverse effect (AE), followed by disease recurrence (15%).

What Was the Safety Profile of Perioperative Tiragolumab Plus Atezolizumab With or Without Chemotherapy?

In the neoadjuvant phase, in cohort A (n = 7), any-grade AEs occurred in all patients, with 43% of effects grade 3 or 4. Treatment-related AEs (TRAEs) were reported in all patients, with 29% of effects grade 3 or 4. Seventy-one percent of patients experienced AEs of special interest. In cohort B, any-grade AEs were experienced by 98% of patients, 39% of which were grade 3 or 4, and 5% of which were grade 5. TRAEs occurred in 93% of patients, with 32% grade 3 or 4 and 2% grade 5. AEs of special interest were observed in 68% of patients. AEs led to treatment withdrawal of any treatment for 10% of patients, for tiragolumab plus atezolizumab for 7% of patients, and chemotherapy for 5% of patients.

In the adjuvant phase, in cohort A (n = 5), any grade AEs and TRAEs occurred in all patients; AEs of special interest occurred in 40% of patients. Surgery-related AEs within 30 days following surgery were experienced by 57% of patients; they were grade 3 or 4 for 14% of patients. In cohort B, 91% of patients experienced any-grade AEs; 27% of these effects were grade 3 or 4, and 6% were grade 5. TRAEs occurred in 73% of patients, with 21% of the effects grade 3 or 4 and 3% grade 5. Sixty-one percent of patients had AEs of special interest. AEs led to withdrawal of tiragolumab plus atezolizumab for 33% of patients. Surgery-related AEs within 30 days following surgery were experienced by 36% of patients; they were grade 3 or 4 for 3% of patients and grade 5 for 3% of patients.

Disclosures: Shu declared serving on advisory boards for AstraZeneca, EMD Serono, Gilead, and Johnson & Johnson, and being a presenter for Curio, OncLive, PeerView, Plexus Communication, and Peer Education.

References

1. Pass H, Felip E, Shu CA, et al. SKYSCRAPER-05: phase II study of perioperative tiragolumab + atezolizumab ± chemotherapy in locally advanced resectable NSCLC. Presented at: International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer; September 6-9, 2025; Barcelona, Spain. Abstract OA02.01.
2. A study evaluating the safety and efficacy of neoadjuvant and adjuvant tiragolumab plus atezolizumab, with or without platinum-based chemotherapy, in participants with previously untreated locally advanced resectable stage II, IIIA, or select IIIB non-small cell lung cancer. ClinicalTrials.gov. Updated March 18, 2025. Accessed September 8, 2025. https://www.clinicaltrials.gov/study/NCT04832854