Tiragolumab Plus Atezolizumab Fails to Meet OS End Point in PD-L1–High NSCLC

First-line treatment with tiragolumab (MTIG7192A) plus atezolizumab (Tecentriq) did not lead to a significant improvement in overall survival (OS) vs atezolizumab monotherapy in PD-L1–high, locally advanced or metastatic non–small cell lung cancer (NSCLC), according to an announcement from Roche.¹

Updated results from the final analysis of the phase 3 SKYSCRAPER-01 trial (NCT04294810) failed to confirm the positive trend for OS seen in previously reported data from the second interim analysis of SKYSCRAPER-01, in which the combination produced an estimated median OS of 22.9 months (95% CI, 17.5–not evaluable) vs 16.7 months (95% CI, 14.6-20.2) with atezolizumab (HR, 0.81; 95% CI, 0.63-1.03) at a median follow-up of 15.5 months.² Notably, OS data were immature at the data cutoff of November 2022.

In the final analysis, tiragolumab plus atezolizumab displayed a safety profile which was consistent with that of prior reports, and no new safety signals were observed.¹

The company stated in a news release that it “continuously reviews its study programs to determine if any adjustments are necessary for the purposes of ongoing research [and] will apply the same principles to this program, with additional data from phase III studies across different settings or tumor types anticipated next year.”

In the same release, the company shared that they plan to present more detailed data from the final analysis at an upcoming medical meeting in 2025.

SKYCRAPER-01 Overview

The global, randomized, double-blind clinical trial enrolled 534 patients with histologically or cytologically confirmed PD-L1–high locally advanced, unresectable or metastatic NSCLC who were not eligible for curative surgery and/or definitive radiotherapy with or without chemoradiation. Furthermore, to be eligible for enrollment, patients were required to be at least 18 years of age, 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.³

Upon enrollment, participants were randomly assigned 1:1 to receive either 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. Patients continued until disease progression, loss of clinical benefit, or unacceptable toxicity on their respective treatment arms.

The study’s co-primary end points were OS and progression-free survival (PFS) in the primary analysis set. Key secondary end points included OS and PFS in the secondary analysis set, confirmed objective response rate, duration of response, PFS rate at 6 and 12 months, OS rate at 12 and 24 months, and time to confirmed deterioration.

In May 2022, Roche announced that the combination did not produce a significant PFS benefit vs atezolizumab alone in SKYSCRAPER-01.⁴

Tiragolumab plus atezolizumab also failed to significantly improve OS or PFS vs pembrolizumab (Keytruda) and chemotherapy in the phase 2/3 SKYCRAPER-06 study (NCT04619797) evaluating patients with previously untreated, locally advanced unresectable or metastatic, PD-L1-selected NSCLC.⁵ Accordingly, Roche discontinued the trial in July 2024.

In January 2021, the FDA granted breakthrough designation to the combination for the frontline treatment of patients with metastatic, PD-L1–high, EGFR and ALK wild-type NSCLC based on data from the phase 2 CITYSCAPE trial (NCT03563716).⁶

In extensive-stage small cell lung cancer, tiragolumab was evaluated alongside atezolizumab, carboplatin, and etoposide in the phase 3 SKYSCRAPER-02 trial (NCT04256421) and did not meet the study’s co-primary end point of improved PFS vs atezolizumab plus chemotherapy alone.⁷

References

1. Roche reports update on phase III SKYSCRAPER-01 study results. News release. Roche. November 26, 2024. Accessed November 26, 2024. https://www.roche.com/media/releases/med-cor-2024-11-26
2. 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 November 26, 2024. roche.com/media/releases/med-cor-2023-08-23
3. 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 November 26, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT04294810
4. 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 November 26, 2024. https://www.roche.com/media/releases/med-cor-2022-05-11
5. Genentech provides update of phase 2/3 Skyscraper-06 study in metastatic nonsquamous non–small cell lung cancer. News release. Genentech. July 3, 2024. November 26, 2024. https://www.gene.com/media/press-releases/15029/2024-07-03/genentech-provides-update-on-phase-iiiii
6. 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 November 26, 2024. https://www.roche.com/media/releases/med-cor-2021-01-05
7. Roche provides update on phase III SKYSCRAPER-02 study in extensive-stage small cell lung cancer. News release. Roche; March 30, 2022. Accessed November 26, 2024. https://www.roche.com/media/releases/med-cor-2022-03-30