Exploratory biomarker analysis of ociperlimab (OCI) plus tislelizumab (TIS) in patients (pts) with PD-L1–positive non–small cell lung cancer (NSCLC) in AdvanTIG-105.

Abstract

2571 Background: OCI (anti-TIGIT) plus TIS (anti-PD-1) may enhance antitumor immune responses in advanced solid tumors. We present a retrospective biomarker analysis of pts in AdvanTIG-105 (NCT04047862), a phase 1/1b open-label study of OCI plus TIS for treatment-naïve metastatic non-squamous (NSQ) and squamous (SQ) PD-L1-positive (TC ≥1%) NSCLC. Methods: Pts in cohort 3 (n=46) were treated with 900 mg OCI plus 200 mg TIS. Pts in cohort 10 (n=68) were treated with 450 mg (Arm A), 900 mg (Arm B), or 1800 mg (Arm C) OCI plus 200 mg TIS. Baseline tumor tissue was used to measure PD-L1 and TIGIT expression (SP263 and SP410 IHC assays). Gene expression profiling (GEP) was performed using TrueSeq RNA Access (Illumina); gene signature scores were evaluated with ssGSEA. Progression-free survival (PFS) hazard ratio (HR) was calculated by Cox proportional hazards regression. Results: At Aug 2024 data cutoff, median follow-up was 19.7 months (range: 0.7-41.6 mo) for cohort 3 and 9.8 mo (range: 0.3-21.4 mo) for cohort 10. Baseline characteristics, overall response rate (ORR), and PFS were comparable across cohorts and between biomarker-evaluable and intent-to-treat (ITT) pts. PD-L1 ≥25% vs <25% and TIGIT ≥5% vs <5% subgroups were associated with a trend toward higher ORR and longer PFS, with greater increment in pts with NSQ- vs SQ-NSCLC (Table). PD-L1/TIGIT double high subgroup showed further enriched clinical efficacy in NSCLC (Table). Anti-TIGIT mechanism of action-related GEP signatures (NK cells, Treg, macrophages) were associated with a trend toward longer PFS primarily in pts with NSQ-NSCLC. Conclusions: Pts with NSCLC with PD-L1 ≥25%, TIGIT ≥5%, or PD-L1/TIGIT double high can achieve a trend toward longer PFS and higher ORR than PD-L1 low or TIGIT low subgroups when treated with OCI plus TIS. Longer PFS in PD-L1 ≥25% or TIGIT ≥5% subgroups in NSQ- vs SQ-NSCLC may be associated with biological differences in histology. Confirmation of these results will require prospective evaluation of OCI plus TIS in randomized studies. Clinical trial information: NCT04047862 . Subgroup mPFS (mo) ORR (%) NSCLC Evaluable pts (n=113) 5.5 34.5 PD-L1 ≥25% vs <25%(n=57 vs 56) 6.9 vs 4.2HR 0.58 (95% CI: 0.37-0.9) 47 vs 22 TIGIT ≥5% vs <5%(n=62 vs 48) 6.8 vs 4.1HR 0.64 (95% CI: 0.41-1) 45 vs 19 PD-L1/TIGIT double positive vs other(n=38 vs 72) 8.3 vs 4.2HR 0.53 (95% CI: 0.33-0.86) 55 vs 22 NSQ-NSCLC PD-L1 ≥25% vs <25%(n=35 vs 32) 8.3 vs 4.2HR 0.55 (95% CI: 0.32-0.98) 49 vs 19 TIGIT ≥5% vs <5%(n=36 vs 29) 6.5 vs 4.1HR 0.53 (95% CI: 0.3-0.94) 50 vs 14 SQ-NSCLC PD-L1 ≥25% vs <25%(n=22 vs 24) 5.5 vs 5.3HR 0.63 (95% CI: 0.35-1.29) 45 vs 25 TIGIT ≥5% vs <5%(n=26 vs 19) 5.5 vs 5.5HR 0.93 (95% CI: 0.46-1.87) 38 vs 26