Trial results for a Phase 3 study (NCT04256421) investigating atezolizumab plus carboplatin and etoposide with or without tiragolumab in patients with untreated extensive-stage small cell lung cancer (ES-SCLC) were posted on ClinicalTrials.gov on 2025-10-22. The study found no significant improvement in progression-free survival (PFS) or overall survival (OS) with the addition of tiragolumab to the atezolizumab-based regimen.

Background

Atezolizumab is an immunotherapy approved for various cancers, including extensive-stage small cell lung cancer. This study aimed to explore whether adding tiragolumab to the standard atezolizumab and chemotherapy regimen could further enhance outcomes for patients with untreated extensive-stage small cell lung cancer.

Trial design

The study (NCT04256421) was a Phase 3 trial that enrolled 490 participants with untreated extensive-stage small cell lung cancer. Participants were randomly assigned to one of two treatment regimens: Arm A received placebo plus atezolizumab, carboplatin, and etoposide, while Arm B received tiragolumab plus atezolizumab, carboplatin, and etoposide. The trial evaluated the efficacy of adding tiragolumab to the atezolizumab-based chemotherapy regimen.

Key results

The trial results showed that the addition of tiragolumab did not significantly improve key efficacy endpoints. For progression-free survival (PFS) in the Full Analysis Set (FAS), the median PFS was 5.42 months for the placebo + atezolizumab arm and 5.06 months for the tiragolumab + atezolizumab arm. The Log Rank analysis for PFS yielded a Hazard Ratio (HR) of 1.08 (95.0% Confidence Interval: 0.89 to 1.31) with a p-value of 0.444, indicating no statistically significant difference.

For overall survival (OS) in the FAS, the median OS was 12.91 months for the placebo + atezolizumab arm and 12.75 months for the tiragolumab + atezolizumab arm. The Log Rank analysis for OS showed an HR of 1.09 (95.0% Confidence Interval: 0.88 to 1.35) with a p-value of 0.4205, also demonstrating no statistically significant difference.

Regarding objective response rate (ORR), the investigator-assessed confirmed ORR in the Per-Protocol Analysis Set (PAS) was 66.7 percentage of participants for the placebo + atezolizumab arm and 73.5 percentage of participants for the tiragolumab + atezolizumab arm. In the FAS, the ORR was 65.6 percentage of participants for the placebo + atezolizumab arm and 70.8 percentage of participants for the tiragolumab + atezolizumab arm. The Cochran-Mantel-Haenszel analysis for the difference in ORR in the PAS was 6.8 percentage of participants (95.0% Confidence Interval: -2.57 to 15.99) with a p-value of 0.1418. For the FAS, the difference was 5.19 percentage of participants (95.0% Confidence Interval: -3.33 to 13.61) with a p-value of 0.2191, neither reaching statistical significance.

The median duration of response (DOR) in the PAS was 5.59 months for the placebo + atezolizumab arm and 4.19 months for the tiragolumab + atezolizumab arm. In the FAS, the median DOR was 5.11 months for the placebo + atezolizumab arm and 4.17 months for the tiragolumab + atezolizumab arm.

What this means

The results of this Phase 3 study indicate that adding tiragolumab to an atezolizumab, carboplatin, and etoposide regimen does not provide additional clinical benefit in patients with untreated extensive-stage small cell lung cancer. The lack of statistically significant improvements in progression-free survival, overall survival, and objective response rates suggests that this combination may not be a more effective treatment strategy than the atezolizumab-based chemotherapy alone for this patient population.

Source

The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT04256421, titled "A Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients With Untreated Extensive-Stage Small Cell Lung Cancer," were posted on 2025-10-22 on clinicaltrials.gov.