1194TiP AdvanTIG-205: Phase II trial of ociperlimab (OCI) + tislelizumab (TIS) + chemotherapy (chemo) in first line (1L) treatment of patients (pts) with locally advanced (LA), unresectable, or metastatic non-small cell lung cancer (mNSCLC)

T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is a co-inhibitory immune checkpoint receptor upregulated on T cells and natural killer cells in multiple solid tumors. Early phase clinical trials have shown antitumor activity of anti-TIGIT monoclonal antibodies (mAbs) + anti-programmed cell death protein 1 (PD-1) mAbs in pts with mNSCLC. OCI is a humanized mAb designed to bind to Fc-intact TIGIT with high affinity and specificity. In China, TIS, an anti-PD-1 mAb, is approved for 2/3L treatment of LA/mNSCLC, and 1L treatment of NSCLC with chemo. AdvanTIG-205 is a Phase 2 study (NCT05014815) designed to assess the efficacy and safety of OCI + TIS + chemo in 1L treatment of pts with LA, unresectable or mNSCLC. Approximately 270 pts with histologically/cytologically confirmed squamous (sq) or non-squamous (non-sq) NSCLC, with no prior systemic therapy for advanced disease, and in whom driver mutation-directed therapy is not indicated, will be enrolled. Eligible pts will be randomized 1:1 to receive intravenous (IV) OCI 900 mg or placebo, with TIS 200 mg IV + chemo every 3 weeks (Q3W) for 4–6 cycles during the induction phase. For pts with sq NSCLC, chemo includes carboplatin (area under the concentration-time curve [AUC] 5 or 6, day [D] 1) + paclitaxel (P; 175 mg/m2 or 200 mg/m2, D1) or nab-P (100 mg/m2, D1, D8 and D15) Q3W. For pts with non-sq NSCLC, chemo includes cisplatin (75 mg/m2, D1) or carboplatin (AUC 5, D1) + pemetrexed (500 mg/m2, D1) Q3W. For maintenance, pts will receive OCI or placebo, with TIS (+ pemetrexed for pts with non-sq NSCLC). Treatment will continue until intolerable toxicity, withdrawal of informed consent, or absence of benefit. Primary endpoint is progression-free survival in the intent-to-treat analysis set (per investigator [INV]; RECIST v1.1). Secondary endpoints include overall response rate, duration of response (both per INV; RECIST v1.1), overall survival, and safety. Exploratory endpoints include disease control rate, biomarker status and health related quality of life. This study is recruiting. Prof. B. Zhu and Prof. T. M. Kim have contributed equally to the study. NCT05014815. This study was sponsored by BeiGene, Ltd. Medical writing support, under the direction of the authors, was provided by Victoria Dagwell, MSc, and Helena Crisford, MSc, of Ashfield MedComms, an Ashfield Health company, and was funded by BeiGene, Ltd. BeiGene, Ltd. BeiGene, Ltd.