Pre-op tiragolumab plus atezolizumab viable in advanced NSCLC

Neoadjuvant treatment with tiragolumab plus atezolizumab, with or without chemotherapy, is feasible in advanced resectable non-small cell lung cancer (NSCLC), having an acceptable safety profile and yielding major pathologic response (MPR) rates comparable to that observed with other perioperative immunotherapy plus chemotherapy regimens, according to the phase II SKYSCRAPER-05 trial.

Over a median follow-up of 9.5 months, the MPR rates were 71 percent in the cohort of patients with high PD-L1 expression who received neoadjuvant tiragolumab plus atezolizumab (cohort A) and 51 percent in the all-comer cohort who received the same neoadjuvant combination with chemotherapy (cohort B). [Pass H, et al, WCLC 2025]

In cohort B, good MPR rates were seen across all PD-L1 subgroups (<1 percent: 43 percent; 1–49 percent: 60 percent; ≥50 percent: 63 percent), reported one of the study authors Dr Catherine Shu from Columbia University, New York in New York, US.

Pathologic complete response (pCR) was achieved in 29 percent of patients each in cohorts A and B. In the PD-L1 <1 percent, 1–49 percent, and ≥50 percent subgroups in cohort B, the respective pCR rates were 22 percent, 20 percent, and 63 percent.

The 24-month event-free survival rates were 86 percent in cohort A and 60 percent in cohort B.

Surgical procedures

Resection was performed in 96 percent of patients overall. Of these, 4 percent received a pneumonectomy, 7 percent received a bilobectomy, 85 percent received a lobectomy, 2 percent received a segmentectomy, and 2 percent received other procedure. The median follow-up was 15.1 months.

Most patients (93 percent) achieved clear surgical margins (R0), and 7 percent had an R1 status.

“There were only two patients who did not undergo surgery due to progression of disease,” Shu noted.

“In terms of surgical delays, there was only one true surgical delay, which was due to grade 3 thrombocytopenia attributed to the chemotherapy. All other delays [n=3] were less than 60 days from the last neoadjuvant dose to surgery,” she added.

Safety summary

In the neoadjuvant treatment phase, adverse events (AEs) occurred in 100 percent of patients in cohort A and in 98 percent in cohort B, of which 43 percent and 39 percent were grade 3–4, respectively. Grade 3–4 treatment-related AEs were reported in 29 percent of patients in cohort A and in 32 percent in cohort B. AEs led to treatment withdrawal in 10 percent of patients in cohort B and none in cohort A.

In the adjuvant treatment phase, AEs occurred in 100 percent of patients in cohort A and in 91 percent in cohort B, of which 0 percent and 27 percent were grade 3–4. The rates of grade 3–4 treatment-related AEs were 0 percent and 21 percent, respectively. AEs led to treatment withdrawal in 33 percent of patients in cohort B and none in cohort A.

Overall and across cohorts, the majority of the AEs of special interest were grade 1 to 2 in severity, according to Shu. Rash was the most common (52 percent), followed by hepatic lab abnormalities (31 percent) and hypothyroidism (21 percent). Infusion-related reactions were seen in about 6 percent of patients.

Two patients in cohort B experienced grade 5 treatment-related AEs. One had infectious pleural effusion in the neoadjuvant phase, while the other had an unexplained death in the adjuvant phase that was deemed treatment-related by the investigator, Shu noted. There was also one surgery-related grade 5 AE due to respiratory distress in cohort B.

SKYSCRAPER-05

SKYSCRAPER-05 included 50 patients with resectable stage II/IIIA/select IIIB (T3N2) patients with NSCLC without EGFR mutations or ALK translocations. These patients had received no prior immunotherapy, chemotherapy, or radiotherapy, had an ECOG performance status of 0 or 1, and had tissue samples available for PD-L1 status testing.

Of the patients, eight were in cohort A and 42 were in cohort B. Cohort A received intravenous tiragolumab 600 mg plus intravenous atezolizumab 1,200 mg once every 3 weeks for 4 cycles in the neoadjuvant phase. Cohort B received the same regimen at the same schedule in addition to platinum-based chemotherapy.

Following the neoadjuvant treatment, resection was performed, with subsequent MPR/pCR assessment. In the adjuvant phase, cohort A received tiragolumab plus atezolizumab once every 3 weeks for 16 cycles or platinum-based chemotherapy once every 3 weeks for 4 cycles. Cohort B received tiragolumab plus atezolizumab every 3 weeks for 16 cycles.

The primary endpoint was safety and MPR. Secondary endpoints included pCR and investigator-assessed EFS. MPR and pCR evaluated by a local pathology lab.