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Background The phase 2 KEYVIBE-002 study ( NCT04725188) investigated the coformulation of the TIGIT antibody vibostolimab with the anti-PD-1 antibody pembrolizumab (vibo/pembro) with or without docetaxel in mNSCLC previously treated with anti-PD-(L)1 therapy and platinum chemotherapy. No significant difference in PFS was observed between vibo/pembro with or without docetaxel versus docetaxel alone. We present an exploratory biomarker analysis examining PD-L1 tumor proportion score (TPS; as a continuous score and ≥1% vs <1%) and TIGIT immunohistochemical (IHC) level (≥median vs <median) as correlates of clinical outcomes in KEYVIBE-002.Methods Adults with pathologically confirmed mNSCLC without EGFR/ALK/ROS1 alterations, PD after 1 prior anti-PD-(L)1 therapy (PD ≤12 weeks from last dose) and platinum-doublet chemotherapy (received concurrently or sequentially), and measurable disease per RECIST v1.1 were enrolled. Participants were randomized 1:1:1 to vibostolimab 200 mg/pembrolizumab 200 mg plus docetaxel Q3W (arm 1; blinded), vibo/pembro alone (arm 2; open label), or placebo plus docetaxel (arm 3; blinded). PD-L1 expression was assessed using PD-L1 IHC 22C3 pharmDx (Agilent, Carpinteria, CA) and reported as TPS. TIGIT protein expression was assessed by IHC (clone SP410, formulation locked assay) and reported as the percentage of immune cells presenting TIGIT (TIGIT-positive) over tumor area. Associations of PD-L1 TPS and TIGIT IHC with PFS and OS for arms 1 and 2 versus 3 were assessed using an adjusted Cox proportional hazards model; statistical significance was determined at one-sided α=0.05 without multiplicity adjustment.Results Of 255 participants, 87 were randomized to arm 1, 83 to arm 2, and 85 to arm 3. Median time from randomization to data cutoff (January 26, 2023) was 12.3 (range, 6.2–19.8) months. PFS and OS results by biomarker subgroups are presented in table 1. There was no evidence of an association between PD-L1 TPS and PFS (arm 1, P=0.664; arm 2, P=0.756; arm 3, P=0.520) or OS (arm 1, P=0.327; arm 2, P=0.163; arm 3, P=0.661). Higher TIGIT IHC was associated with improved PFS (nominal one-sided P=0.009) and OS (P=0.009) in arm 1 but not in arm 2 (PFS, P=0.224; OS, P=0.679) or arm 3 (PFS, P=0.214; OS, P=0.056). Additional biomarker data will be presented.Conclusions These biomarker analyses showed that higher TIGIT IHC was associated with numerically longer PFS and OS in participants with mNSCLC previously treated with an anti-PD-(L)1 and platinum-based chemotherapy receiving vibo/pembro with docetaxel; this benefit was not observed with vibo/pembro alone.Trial Registration ClinicalTrials.gov identifier, NCT04725188Ethics Approval The study was conducted in accordance with principles of Good Clinical Practice and approved by the appropriate institutional review boards and regulatory agencies. All participants provided written informed consent before enrolling.Abstract 508 Table 1PFS and OS HRa estimates for biomarker subgroupsNE, indicates a bound of the CI does not exist; NR, not reached. aHRs were estimated using Cox proportional hazards models with extra covariate(s) of ECOG 0 or >0. bThe default method to calculate the Cl of time-to-event data is log-log.