969TiP Randomized, phase III study of MK-7684A plus concurrent chemoradiotherapy (cCRT) followed by MK-7684A vs cCRT followed by durvalumab for unresectable, locally advanced, stage III non-small cell lung cancer (NSCLC): KEYVIBE-006

Abstract

Pembrolizumab (pembro; anti‒PD-1) + cCRT demonstrated robust antitumor activity and manageable safety in the KEYNOTE-799 study in previously untreated, locally advanced, stage III NSCLC. The combination of vibostolimab (MK-7684; monoclonal antibody that inhibits T-cell immunoglobulin and ITIM domain [TIGIT] immunomodulatory receptor) + pembro with/without chemotherapy (chemo) has shown promising antitumor activity with manageable safety in patients (pts) with advanced NSCLC in the KEYVIBE-001 study. The KEYVIBE-006 study (NCT05298423) is evaluating MK-7684A (co-formulation of vibostolimab + pembro) + cCRT followed by MK-7684A vs cCRT followed by durvalumab (anti‒PD-L1) in unresectable, locally advanced, stage III NSCLC. In this phase 3, open-label, randomized study, ∼784 eligible adults with previously untreated, unresectable, pathologically confirmed stage IIIA‒C NSCLC; measurable disease by RECIST v1.1; and ECOG PS of 0/1 will be randomized 1:1. In arm A, pts receive intravenous (IV) MK-7684A (vibostolimab 200 mg + pembro 200 mg) Q3W + 3 cycles of chemo (one of: cisplatin 75 mg/m2 + pemetrexed 500 mg/m2 [nonsquamous only]; cisplatin 50 mg/m2 + etoposide 50 mg/m2; or carboplatin AUC 6 mg/mL/min [cycle 1] and AUC 2 mg/mL/min [cycles 2/3] + paclitaxel 200 mg/m2 [cycle 1] and 45 mg/m2 [cycles 2/3]) + standard thoracic radiotherapy (TRT; 60 Gy in 2-Gy fractions; cycles 2/3) followed by vibostolimab 200 mg + pembro 200 mg for up to 17 cycles. Pts in arm B receive 3 cycles of chemo + TRT (as above) followed by durvalumab 10 mg/kg IV Q2W for up to 26 cycles. Treatment continues until treatment completion, PD, unacceptable toxicity, or investigator decision. Randomization is stratified by histology (squamous vs nonsquamous), stage (IIIA vs IIIB/IIIC), PD-L1 TPS (<1% vs ≥1%), and region (East Asia vs North America/Western Europe/Australia vs rest of world). Dual primary endpoints are PFS per RECIST v1.1 by blinded independent central review (BICR) and OS. Secondary endpoints include ORR and DOR per RECIST v1.1 by BICR, safety, and patient-reported outcomes. Enrollment began in May 2022. NCT05298423 Medical writing support was provided by Christabel Wilson, MSc, of ICON plc (Blue Bell, PA, USA). Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.