SKYSCRAPER-01 Trial Misses Co-Primary End Point of PFS in PD-L1-High NSCLC


The SKYSCRAPER-01 study missed its co-primary end point of progression-free survival in patients with PD-L1-high, locally advanced or metastatic non-small cell lung cancer.

The phase 3 SKYSCRAPER-01 study (NCT04294810) evaluating the addition of tiragolumab to atezolizumab (Tecentriq) as first-line treatment for people with PD-L1-high, locally advanced or metastatic non-small cell lung cancer (NSCLC) did not meet its co-primary end point of progression-free survival (PFS), according to Roche.1

This first analysis also revealed that data for the other co-primary end point of overall survival (OS) was immature. The study will continue until the next planned analysis.

Both co-primary end points did demonstrate a numerical improvement, and data suggested that the combination of tiragolumab plus atezolizumab was well-tolerated. Further, no new safety signals were identified with the addition of tiragolumab.

“While these results are not what we hoped for in our first analysis, we look forward to seeing mature overall survival for this study to determine next steps,” said Levi Garraway, MD, PhD, Roche’s chief medical officer and head of global product development, in the press release. “We continue to believe that TIGIT may have a role in cancer treatment and we will share additional results from our tiragolumab program as they emerge.”

Tiragolumab is an investigational anti-TIGIT immunotherapy that works by binding to TIGIT, an inhibitory immune checkpoint that lessens the immune response to cancer. Preclinical research has shown tiragolumab to work as an immune amplifier when paired with other cancer immunotherapies, including atezolizumab.

Atezolizumab, a cancer immunotherapy, is currently approved for various aggressive and difficult-to-treat forms of cancer, including NSCLC, small cell lung cancer, and hepatocellular carcinoma. The monoclonal antibody binds with a protein called programmed death ligand-1 to PD-L1, and blocks its interactions with both PD-1 and B7.1 receptors. Then, atezolizumab may enable the activation of T cells.

Experts hope the dual blockade with tiragolumab and atezolizumab may aid in overcoming immune suppression and work to restore the immune response.

The randomized, double-blind, placebo-controlled, phase 3 study is evaluating tiragolumab plus atezolizumab vs atezolizumab alone. A total of 534 patients with first-line, PD-L1-high, locally advanced, unresectable or metastatic NSCLC were randomized 1:1 to receive either the combination of tiragolumab and atezolizumab or placebo plus atezolizumab.2

In the experimental arm, participants were administered 1200 mg atezolizumab intravenously (IV) plus 600 mg tiragolumab IV on day 1 of each 21-day cycle. The placebo comparator arm recieved a matching dose of atezolizumab alone.

Enrollment in the trial is open to patients aged 18 years and older with histologically or cytologically documented locally advanced or recurrent NSCLC who are not eligible for curative surgery and/or definitive radiotherapy with or without chemoradiotherapy. Patients must have no prior systemic treatment for metastatic NSCLC, high tumor tissue PD-L1 expression, measurable disease per RECIST v1.1, adequate hematologic and end-organ function, and an ECOG status of 0 or 1. For those enrolled in the extended China enrollment phase, participants must be a current resident of mainland China or Taiwan and of Chinese ancestry.

Key primary end points of the trial were PFS and OS, with secondary end points including objective response rate, duration of response, time to confirmed deterioration, adverse events, maximum and minimum of serus concentration of both tiragolumab and atezolizumab, and percentage of participants with anti-drug antibodies. 

The tiragolumab program continues to explore advances in multiple clinical trials to build on atezolizumab and to provide new treatment options in advanced cancers with high unmet medical need. Further analyses of results from the trial are ongoing and data are planned to be presented at an upcoming medical meeting.

  1. Roche News Release. Roche reports interim results for phase III SKYSCRAPER-01 study in PD-L1-high metastatic non-small cell lung cancer. Published: May 11, 2022. Accessed May 12, 2022.
  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). Updated: December 7, 2022. Accessed May 12, 2022.
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