The phase 3 KEYVIBE-008 trial evaluating the co-formulated therapy of vibostolimab and pembrolizumab (Keytruda) plus etoposide and platinum (EP) in patients with extensive-stage small cell lung cancer (ES-SCLC) has met its pre-specified futility criterion for the primary endpoint of overall survival (OS). The trial's results, presented at the 2024 SITC Annual Meeting, indicated that the investigational regimen did not demonstrate a statistically significant improvement in OS compared to the control arm of atezolizumab (Tecentriq) plus EP.
Efficacy and Outcomes
The median OS for patients receiving vibostolimab/pembrolizumab plus chemotherapy was 11.5 months (95% CI, 9.8-12.6) compared to 12.9 months (95% CI, 11.6-14.8) for those receiving atezolizumab plus chemotherapy (HR, 1.26; 95% CI, 1.00-1.59; P = .9762). Progression-free survival (PFS), a secondary endpoint, was 5.3 months (95% CI, 4.4-5.4) in the investigational arm and 4.5 months (95% CI, 4.4-5.3) in the control arm (HR, 1.01; 95% CI, 0.82-1.23).
According to Jacob Sands, MD, lead study author, assistant professor at Harvard Medical School, and Oncology Medical Director of the International Patient Center at Dana-Farber Cancer Institute in Boston, Massachusetts, treatment with vibostolimab/pembrolizumab was discontinued in the KEYVIBE-008 trial based on the benefit/risk profile observed. He also noted that investigation of vibostolimab/pembrolizumab is ongoing in non–small cell lung cancer (NSCLC).
The trial enrolled patients with newly diagnosed, previously untreated ES-SCLC, with an ECOG performance status of 0 or 1. Patients were randomized 1:1 to receive either vibostolimab/pembrolizumab plus etoposide and cisplatin/carboplatin or atezolizumab plus etoposide and cisplatin/carboplatin. Treatment was administered every 3 weeks for 4 cycles, followed by maintenance with vibostolimab/pembrolizumab or atezolizumab until disease progression or unacceptable toxicity.
Safety Profile
The safety analysis revealed that grade 3 or greater treatment-related adverse events (TRAEs) were more frequent in the vibostolimab/pembrolizumab arm (66.8%) compared to the atezolizumab arm (57.2%). Immune-mediated adverse events were also more common in the investigational arm (14.8%) versus the control arm (3.5%). Common TRAEs in the vibostolimab/pembrolizumab arm included anemia (61.6%), neutropenia (56.8%), and leukopenia (41.0%).
Trial Design and Patient Characteristics
KEYVIBE-008 was a double-blind trial involving patients aged 18 years or older with previously untreated ES-SCLC. The primary endpoint was OS, with secondary endpoints including PFS, ORR, and DOR. The median patient age was 64 years in the investigational arm, with the majority having stage IVB disease (60.0%) and a history of smoking (91.7%).
Implications for ES-SCLC Treatment
Despite previous evidence suggesting potential efficacy, including findings from the KEYNOTE-604 trial, the KEYVIBE-008 trial did not demonstrate a survival benefit with the addition of vibostolimab to pembrolizumab and chemotherapy in ES-SCLC. The results highlight the challenges in improving outcomes for this aggressive cancer and underscore the need for continued research into novel therapeutic strategies.
