First-Line Tiragolumab Combo Misses PFS Co-Primary End Point in ES-SCLC

Treatment with a combination of tiragolumab plus atezolizumab (Tecentriq) and chemotherapy in the first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) missed the co-primary end point of the phase 3 SKYSCRAPER-02 (NCT04256421), according to a press release from Roche.¹

In addition to not meeting the co-primary end point of progression-free survival (PFS), the combination also missed its other primary end point of overall survival (OS) at the interim analysis. Moreover, investigators determined that OS was unlikely to reach statistical significance by the planned final analysis, although the combination was found to be well tolerated with no emergent safety findings.

Data from the trial is set to read out at an upcoming medical meeting.

“Today’s outcome is disappointing as we had hoped to continue building on the advances of [atezolizumab] in [ES-SCLC], which remains difficult to treat. We are thankful to all the patients and healthcare professionals involved in the study,” Levi Garraway, MD, PhD, chief medical officer and head of global product development, said in the press release. “We look forward to seeing additional data from the upcoming phase 3 trial in PD-L1–high non–small cell lung cancer [NSCLC] based on the encouraging results from the [phase 2] CITYSCAPE study [NCT03563716].”

The anti–T-cell immunoreceptor with Ig and ITIM domains, or TIGIT, immunotherapy agent is also being examined in other clinical trials to build on the success seen with atezolizumab with the goal of moving treatment into earlier lines of treatment and providing novel options for the advanced and hard-to-treat populations.

Findings from the CITYSCAPE trial, examining the experimental therapeutic plus atezolizumab in patients with PD-L1–high metastatic NSCLC with no EGFR or ALK aberrations, helped to support a breakthrough therapy designation for tiragolumabin January 2021.² The primary analysis determined that patients treated with the tiragolumab combination experienced an overall response rate of 31.3% (95% CI, 19.5%-43.2%) vs 16.2% (95% CI, 6.7%-25.7%; odds ratio, 2.57; 95% CI, 1.07-6.14). Additionally, the median PFS was 5.4 months (95% CI, 4.2–not evaluable) and 3.6 months (95% CI, 2.7-4.4) in the experimental and placebo groups, respectively (HR, 0.57; 95% CI, 0.37-0.90).

The CITYSCAPE trial findings are in the process of being confirmed in the phase 3 SKYSCRAPER-01 trial comparing tiragolumab and atezolizumab vs placebo and atezolizumab in previously untreated locally advanced unresectable or metastatic PD-L1–positive NSCLC.

The SKYSCRAPER-02 trial enrolled a total of 490 patients. Patients in the experimental arm received 600 mg of tiragolumab on day 1 plus 1200 mg of atezolizumab on day 1, carboplatin on day 1, and 100 mg/m2 of etoposide on days 1 to 3 of every 21-day cycle. Those in the control arm received the same atezolizumab and chemotherapy backbone.

References

1. Ad hoc announcement pursuant to Art. 53 LR Roche provides update on phase III SKYSCRAPER-02 study in extensive-stage small cell lung cancer. News release. Roche. March 30, 2022. Accessed March 31, 2022. https://bit.ly/38j3lHp
2. 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 March 31, 2022. https://bit.ly/3iTziYU