94TiP Neoadjuvant tislelizumab or placebo + platinum-based chemotherapy followed by adjuvant tislelizumab or placebo in patients with resectable non-small cell lung cancer (NSCLC): A phase III trial in progress

Background: Adjuvant and neoadjuvant therapies have been proposed to improve the prognosis of patients (pts) with stage II/IIIA lung cancer but have provided only modest survival benefits. When added to chemotherapy, PD-(L)1 inhibitors have resulted in enhanced antitumor activity versus chemotherapy alone, but their ability to limit relapse in pts who have undergone surgical resection has not yet been fully elucidated. Tislelizumab, a monoclonal antibody with high affinity and specificity for PD-1, was engineered to minimize binding to FcyR on macrophages to abrogate antibody-dependent phagocytosis. Tislelizumab, as a single agent and in combination with chemotherapy, has demonstrated a manageable tolerability profile and efficacy in pts with advanced NSCLC. Trial design: This phase III, randomized, double-blind study (NCT04379635) compares the efficacy of neoadjuvant tislelizumab or placebo + platinum-based doublet chemotherapy followed by adjuvant tislelizumab or placebo. Adult pts (n≈380) with histologically confirmed, squamous (sq) or nonsquamous (nsq) stage II/IIIA resectable NSCLC are eligible; key exclusion criteria include prior systemic anticancer treatment for lung cancer or known EGFR mutations or ALK rearrangements. In the neoadjuvant phase, pts will be randomized 1:1 to receive tislelizumab (Arm A) or placebo (Arm B) plus cisplatin/carboplatin + paclitaxel or pemetrexed on Day 1 of each 3-wk cycle for 3–4 cycles. Patients will be stratified by histology (sq vs nsq), disease stage (II vs IIIA), and PD-L1 expression (≥1% vs <1%). After surgery, adjuvant therapy (tislelizumab [A]; placebo [B]) will be administered on Day 1 of each 6-wk cycle for up to eight cycles. Major pathological response rate (proportion of pts with ≤10% residual viable tumors) and event-free survival per RECIST v1.1 are dual primary endpoints. Secondary endpoints include overall survival, objective response rate, disease-free survival, pathological complete response rate, safety/tolerability (assessed by monitoring incidence and severity of adverse events), and health-related quality-of-life measures. Clinical trial identification: NCT04379635. Editorial acknowledgement: Writing and editorial assistance was provided by Stephan Lindsey, PhD, and Elizabeth Hermans, PhD (OPEN Health Medical Communications, Chicago, IL), and funded by the study sponsor. Legal entity responsible for the study: BeiGene, Ltd. Funding: BeiGene, Ltd. Disclosure: R. Wang: Full/Part-time employment: BeiGene, Ltd. Y. Ma: Full/Part-time employment: BeiGene, Ltd. X. Liang: Full/Part-time employment: BeiGene, Ltd. All other authors have declared no conflicts of interest.