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Roche's Tiragolumab, Tecentriq Combo Misses Overall Survival Endpoint in PD-L1 Positive NSCLC Trial

NEW YORK – Genentech on Tuesday said the Phase III SKYSCRAPER-01 trial of the anti-TIGIT antibody tiragolumab with its anti-PD-L1 drug Tecentriq (atezolizumab) in patients with PD-L1-high, locally advanced or metastatic non-small cell lung cancer did not meet the primary overall survival endpoint.

In the randomized, double-blind trial, the Roche subsidiary compared treatment with tiragolumab and Tecentriq to Tecentriq alone in more than 500 PD-L1-high NSCLC patients. To be eligible for the trial, patients must not have had an EGFR mutation or ALK fusion oncogene and must not have had prior treatment with CD137 agonists, immune checkpoint inhibitors, or antibodies targeting CTLA-4, TIGIT, PD-1, or PD-L1.

Tiragolumab is designed to block interactions between TIGIT, a receptor expressed on T cells and natural killer cells, and certain proteins on tumor cells that help cancers evade an immune system attack. Because TIGIT is co-expressed with PD-1 on those cells, Genentech hypothesized that combining the anti-PD-L1 drug Tecentriq and tiragolumab would enhance patients' immune response against cancer.

Genentech launched the SKYSCRAPER-01 trial in 2020 based on encouraging results from the Phase II CITYSCAPE trial, in which researchers compared tiragolumab-Tecentriq to Tecentriq alone in 135 patients with PD-L1-positive, metastatic NSCLC. In that trial, the subset of patients with PD-L1 scores of 50 percent or more had a 66 percent overall response rate on tiragolumab-Tecentriq compared to 24 percent on Tecentriq alone.

However, SKYSCRAPER-01 faltered in 2022 when it missed its progression-free survival endpoint, and in August 2023, the company reported that at a median follow-up of 15.5 months, median overall survival in the tiragolumab-Tecentriq group was 22.9 months compared to 16.7 months in the Tecentriq monotherapy group with a hazard ratio of 0.81. The firm has continued the trial in the hope that the overall survival trend seen in that analysis would reach statistical significance in the final readout.

In a statement, Genentech said it continuously reviews its programs to determine if adjustments are necessary and that it would apply those principles to tiragolumab, incorporating data from additional Phase III studies in different settings and tumor types that are expected next year.