Tiragolumab Plus Atezolizumab Falls Short in Unexpected OS Analysis in PD-L1–High NSCLC

The addition of the investigational anti-TIGIT immunotherapy tiragolumab to atezolizumab (Tecentriq) demonstrated a numerical but not statistically significant improvement in overall survival (OS) vs atezolizumab alone as frontline therapy for patients with PD-L1–high, locally advanced or metastatic non–small cell lung cancer (NSCLC), according to Roche’s receipt of an inadvertent disclosure of the second interim analysis of the phase 3 SKYSCRAPER-01 trial (NCT04294810).¹

The second interim analysis was conducted in February 2023 and was based on a data cut-off in November 2022. Notably, OS data were not mature at the time of the analysis. At a median follow-up of 15.5 months, the estimated median OS was 22.9 months (95% CI, 17.5–not evaluable) in the combination arm vs 16.7 months (95% CI, 14.6-20.2) in the atezolizumab monotherapy arm (HR, 0.81; 95% CI, 0.63-1.03).

Regarding safety, the combination was well tolerated, and no new safety signals occurred with the addition of tiragolumab to atezolizumab.

The study, which will continue as planned until the final analysis for OS, will stay blinded to patients and investigators. All other studies evaluating tiragolumab will continue unaffected.

SKYSCRAPER-01 is a global, randomized, double-blind, phase 3 study evaluating tiragolumab plus atezolizumab vs atezolizumab alone as first-line treatment in 534 patients with PD-L1–high locally advanced, unresectable or metastatic NSCLC.

To be eligible for enrollment, patients at least 18 years of age had to have measurable disease per RECIST v1.1 criteria, high PD-L1 expression on tumor tissue, an ECOG performance status of 0 or 1, and acceptable hematologic and end-organ function.²

Patients were randomly assigned 1:1 to receive 600 mg of tiragolumab plus 1200 mg of intravenous atezolizumab every 3 weeks on day 1 of each 21-day cycle, or placebo plus atezolizumab until disease progression, loss of clinical benefit, or unacceptable toxicity.

Co-primary end points of the study are OS and progression-free survival (PFS) in the primary analysis set.

Previously, Roche announced that the combination failed to improve PFS vs atezolizumab alone, missing the co-primary end point of the trial.³

In January 2021, the combination received breakthrough designation from the FDA as frontline therapy for patients with metastatic, PD-L1–high, EGFR and ALK wild-type NSCLC.⁴

References

1. [Ad hoc announcement pursuant to Art. 53 LR] Roche provides update on phase III Skyscraper-01 study in PD-L1-high metastatic non-small cell lung cancer. News release. Roche. August 23, 2023. Accessed August 23, 2023. roche.com/media/releases/med-cor-2023-08-23
2. A study of tiragolumab in combination with atezolizumab compared with placebo in combination with atezolizumab in patients with previously untreated locally advanced unresectable or metastatic PD-L1-selected non-small cell lung cancer (SKYSCRAPER-01). ClinicalTrials.gov. Updated August 21, 2023. Accessed August 23, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04294810
3. Roche reports interim results for phase III SKYSCRAPER-01 study in PD-L1–high metastatic non-small cell lung cancer. News release. Roche. May 11, 2022. Accessed August 23, 2023. https://www.roche.com/media/releases/med-cor-2022-05-11
4. Roche’s novel anti-TIGIT tiragolumab granted FDA breakthrough therapy designation in combination with Tecentriq for PD-L1-high non-small cell lung cancer. News release. Roche. January 5, 2021. Accessed August 23, 2023. https://www.roche.com/media/releases/med-cor-2021-01-05