In brief
- KEYVIBE-008 randomised 460 patients with untreated extensive-stage small-cell lung cancer (ES-SCLC) to vibostolimab coformulated with pembrolizumab, or to atezolizumab, each with etoposide and platinum chemotherapy.
- At the prespecified interim analysis, the futility criterion for overall survival was met, with a hazard ratio of 1.26 (P = 0.9762).
- Progression-free survival did not differ (hazard ratio 1.01), and objective response rates were 71.7% with vibostolimab/pembrolizumab and 74.8% with atezolizumab.
- Grade 3 or higher treatment-related adverse events occurred in 66.8% of patients on vibostolimab/pembrolizumab and in 57.2% on atezolizumab.
- Treatment with vibostolimab/pembrolizumab was discontinued on the overall benefit-risk profile.
Study at a glance
- Trial: KEYVIBE-008 (NCT05224141), randomised 1:1
- Population: 460 adults with untreated ES-SCLC, 230 per arm
- Treatment: Vibostolimab 200 mg and pembrolizumab 200 mg, coformulated, every 3 weeks, with etoposide and cisplatin or carboplatin for four cycles
- Comparator: Atezolizumab 1200 mg every 3 weeks with the same chemotherapy
- Primary endpoint: Overall survival
- Overall survival: Hazard ratio 1.26 (95% CI 1.00–1.59; P = 0.9762), futility criterion met
- Progression-free survival: Hazard ratio 1.01 (95% CI 0.82–1.23)
- Objective response: 71.7% vs 74.8%
- Safety: Grade 3 or higher treatment-related adverse events in 66.8% vs 57.2%
- Not reported: In the abstract, median overall or progression-free survival in either arm; duration of response
An active comparator: atezolizumab plus etoposide and platinum
Vibostolimab is an antibody against T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT). Given with pembrolizumab, it had shown antitumour activity in non-small cell lung cancer, and KEYVIBE-008 tested the coformulated pair in first-line ES-SCLC.
Adults with untreated disease were randomised 1:1 to vibostolimab and pembrolizumab, 200 mg each, or to atezolizumab 1200 mg, every 3 weeks. Both arms received etoposide with cisplatin or carboplatin for the first four cycles. The comparator arm is an established first-line regimen in this setting, so the trial asked whether the TIGIT antibody improved on current standard chemoimmunotherapy.
An overall survival hazard ratio of 1.26 at the interim futility analysis
The prespecified interim analysis included a non-binding futility analysis of overall survival, with a threshold of P = 0.4816 for the actual number of events. Median time from randomisation to the data cutoff of 4 June 2024 was 16.6 months (range 11.3–26.1).
The futility criterion was met. The hazard ratio of 1.26 (95% CI 1.00–1.59; P = 0.9762) places the point estimate on the side of the atezolizumab arm.
Progression-free survival and response no different from atezolizumab
The hazard ratio for progression-free survival was 1.01 (95% CI 0.82–1.23). Objective responses were recorded in 71.7% of patients given vibostolimab/pembrolizumab and in 74.8% of those given atezolizumab.
More severe toxicity with the TIGIT combination
Grade 3 or higher treatment-related adverse events occurred in 66.8% of participants treated with vibostolimab/pembrolizumab and in 57.2% of those treated with atezolizumab. The authors also report that immune-mediated adverse events were more frequent with vibostolimab/pembrolizumab than with atezolizumab.
Vibostolimab/pembrolizumab discontinued on the benefit-risk balance
With overall survival meeting the futility criterion and severe treatment-related toxicity higher in the experimental arm, the authors state the consequence for the programme:
“Given the overall benefit/risk profile, treatment with vibostolimab/pembrolizumab was discontinued.”Sands et al., Targeted Oncology (2026)
The results come from an interim analysis, so the survival estimates rest on the events accrued by the June 2024 cutoff.
Sources
- Targeted Oncology. Vibostolimab Coformulated with Pembrolizumab Plus Chemotherapy as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer (2026-10-20). doi.org
Featuring Lung Summit faculty
This study was co-authored by Lung Summit faculty Jacob Sands and Martin Reck.
This article was produced independently by the Lung Summit editorial team, without industry funding or input.
