Tiragolumab/Atezolizumab Does Not Meet OS End Point in Metastatic NSCLC

Tiragolumab with atezolizumab, when compared with placebo with atezolizumab, failed to reach its overall survival end point in patients with NSCLC.

Further results from the phase 3 SKYSCRAPER-01 study (NCT04294810) showed that tiragolumab in combination with atezolizumab (Tecentriq) did not improve overall survival (OS) compared with atezolizumab alone in patients with PD-L1–high, locally advanced or metastatic, non–small cell lung cancer (NSCLC), according to a press release from the developers, Roche.¹

The study did not reach the primary end point of OS at the final analysis, the safety profile remained consistent with longer follow-up, and no new safety signals were identified. More data will be presented at a medical meeting in 2025.

In the press release, the developers stated that they will continuously review their study programs to determine any necessary adjustments for their ongoing research. Additionally, they will apply similar principles to the tiragolumab program and anticipate reporting additional data from phase 3 studies across different settings and disease types next year.

Tiragolumab was designed as a novel immune checkpoint inhibitor with an intact Fc region. The agent is intended to selectively bind to TIGIT, an inhibitory immune checkpoint that can limit the body’s immune response to cancer.

Primary study end points were investigator-assessed progression-free survival (PFS) in the primary analysis set, OS in the primary analysis set, percentage of patients with adverse events (AEs), and percentage of patients with cytokine release syndrome (CRS).² Secondary end points included investigator-assessed objective response rate (ORR) and duration of response.

Interim results published in May 2022 showed that the trial did not meet the primary end point of PFS.³ It was reported then that data for OS were immature, although investigators noted both PFS and OS had numerical improvements in the tiragolumab arm.

The SKYSCRAPER-01 trial was randomized, double-blinded, and enrolled 534 patients with PD-L1–high previously untreated, locally advanced unresectable or metastatic NSCLC. The randomization ratio was 1:1, and patients were sorted into 1 of 2 groups: a tiragolumab with atezolizumab group or a placebo with atezolizumab group. Treatment continued until disease progression, loss of clinical benefit, or unacceptable toxicity.

Regarding dosing, 1200 mg of atezolizumab was administered by intravenous infusion every 3 weeks on day 1 of each 21-day cycle, 600 mg of tiragolumab was administered by intravenous infusion every 3 weeks on day 1 of each 21-day cycle, and the matching placebo was administered every 3 weeks on day 1 of each 21-day cycle.

To be eligible for inclusion, patients needed to be aged 18 years or older, have an ECOG performance status of 0 or 1, have histologically or cytologically documented locally advanced or recurrent NSCLC ineligible for curative surgery and/or definitive radiotherapy with or without chemoradiotherapy, have no prior systemic treatment for NSCLC, and have high tumor tissue PD-L1 expression, among other requirements.

Exclusion criteria included a known mutation in the EGFR gene or an ALK fusion oncogene; symptomatic, untreated, or actively progressing central nervous system (CNS) metastases; active or history of autoimmune disease/deficiency; active hepatitis B or hepatitis C; and prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti–CTLA-4, anti-TGIT, anti–PD-1, and anti–PD-L1 therapeutic antibodies.

The trial was hosted in the following countries: Australia, Austria, Brazil, China, Denmark, Germany, Greece, Hungary, Italy, Japan, Republic of Korea, Mexico, Netherlands, Peru, Poland, Russian Federation, Serbia, Spain, Switzerland, Taiwan, Thailand, Turkey, Ukraine, and the United States.

The trial began on March 4, 2020, and is planned to be completed on February 21, 2025.

References

1. Roche reports update on phase 3 SKYSCRAPER-01 study results. News Release. Roche. November 26, 2024. Accessed November 26, 2024. https://tinyurl.com/2vse8y2n
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 October 10, 2024. Accessed November 26, 2024. https://tinyurl.com/42ee3ecw
3. Roche reports interim results for the phase III SKYSCRAPER-01 study in PD-L1-high metastatic non–small cell lung cancer. News release. Roche. May 11, 2022. Accessed November 26, 2024. https://bit.ly/39e8QY4