1463 Coformulated vibostolimab/pembrolizumab plus chemotherapy as first-line therapy vs atezolizumab plus chemotherapy for extensive-stage small-cell lung cancer (ES-SCLC): randomized, phase 3 KEYVIBE-008

<h3>Background</h3> Etoposide with platinum-chemotherapy (EP) plus immunotherapy (e.g. atezolizumab) is the recommended treatment for ES-SCLC.¹ First-line pembrolizumab plus EP significantly improved PFS but not OS vs placebo plus EP in ES-SCLC in the KEYNOTE-604 study.² Vibostolimab, an anti–T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) antibody, showed antitumor activity with pembrolizumab in NSCLC.³ The KEYVIBE-008 study evaluated vibostolimab coformulated with pembrolizumab (vibostolimab/pembrolizumab) plus EP as first-line therapy for ES-SCLC (NCT05224141). <h3>Methods</h3> Patients (≥18 years) with histologically/cytologically confirmed untreated ES-SCLC were randomized 1:1 to vibostolimab/pembrolizumab (200 mg each) Q3W or atezolizumab 1200 mg Q3W; patients also received EP (cisplatin or carboplatin) for the first 4 cycles. Stratification factors were ECOG PS (0 vs 1), lactate dehydrogenase concentration (≤ULN vs &gt;ULN), liver metastases (yes vs no), and brain metastases (yes vs no). The primary endpoint was OS. Secondary endpoints included PFS, ORR, and duration of response (DOR) per RECIST v1.1 by BICR, and safety. The prespecified interim analysis (data cutoff, June 4, 2024) included a nonbinding futility analysis of OS (futility threshold, P=0.5391). <h3>Results</h3> 460 patients were randomized, with 230 randomized to vibostolimab/pembrolizumab plus EP (vibostolimab/pembrolizumab arm) and 230 to atezolizumab plus EP (atezolizumab arm). Median time from randomization to data cutoff was 16.6 (range, 11.3–26.1) months. Median treatment exposure (range) was 4.9 (0.1–24.2) months for the vibostolimab/pembrolizumab arm and 4.9 (0.1–22.8) for the atezolizumab arm. The study met the prespecified futility criterion for OS (HR, 1.26; 95% CI, 1.00–1.59; P=0.9762; table 1). PFS HR for the vibostolimab/pembrolizumab vs atezolizumab arms was 1.01 (95% CI, 0.82–1.23 ). Confirmed ORR (95% CI) was 71.7% (65.4%–77.5%) and 74.8% (68.7%–80.3%), respectively. Grade ≥3 treatment-related AEs occurred in 153/229 patients (66.8%) in the vibostolimab/pembrolizumab arm and 131/229 patients (57.2%) in the atezolizumab arm; 4 (1.7%) and 2 (0.9%) treatment-related deaths occurred, respectively. Immune-mediated AE s and infusion reactions occurred in 90/229 patients (39.3%) in the vibostolimab/pembrolizumab arm and 68/229 patients (29.7%) in the atezolizumab arm, with 34 (14.8%) and 8 (3.5%), respectively, reported as grade ≥3. <h3>Conclusions</h3> In this interim analysis of vibostolimab/pembrolizumab plus EP vs atezolizumab plus EP as first-line therapy for ES-SCLC, the prespecified futility criterion for the primary endpoint (OS) was met. Grade ≥3 treatment-related AEs and immune-mediated AEs were more frequent with vibostolimab/pembrolizumab vs atezolizumab, consistent with dual immune checkpoint inhibitor therapy. Given the overall benefit/risk profile, treatment with vibostolimab/pembrolizumab was discontinued, and patients were offered atezolizumab. <h3>Acknowledgements</h3> Medical writing assistance was provided by Aisling Towell, of ICON plc (Dublin, Ireland). This assistance was funded by Merck Sharp &amp; Dohme LLC, a subsidiary of Merck &amp; Co., Inc., Rahway, NJ, USA. <h3>Trial Registration</h3> ClinicalTrials.gov, NCT05224141; EudraCT 2021-005034-42. <h3>References</h3> National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). Small Cell Lung Cancer. Version 1.2024. https://www.nccn.org. Accessed September 1 2024. Rudin CM, Awad MM, Navarro A, <i>et al.</i> Pembrolizumab or placebo plus etoposide and platinum as first-line therapy for extensive-stage small-cell lung cancer: randomized, double-blind, phase III KEYNOTE-604 study. <i>J Clin Oncol</i> 2020;<b>38</b>:2369–79. Niu J, Maurice-Dror C, Lee DH, <i>et al.</i> First-in-human phase 1 study of the anti-TIGIT antibody vibostolimab as monotherapy or with pembrolizumab for advanced solid tumors, including non-small-cell lung cancer. <i>Ann Oncol</i> 2022;<b>33</b>:169–80. <h3>Ethics Approval</h3> The study was conducted using Good Clinical Practice guidelines. The study protocol and amendments were approved by the appropriate ethics body at each site. All patients provided written informed consent before enrollment. An external independent data and safety monitoring committee reviewed safety and efficacy data.