1263P Tislelizumab + chemotherapy vs chemotherapy alone as first-line treatment for locally advanced/metastatic nonsquamous NSCLC

Tislelizumab + chemotherapy has shown antitumor activity with a favorable tolerability profile in patients (pts) with histologically confirmed nsq-NSCLC. In this open-label phase 3 study (NCT03663205), Chinese pts were randomized 2:1 to receive tislelizumab 200 mg + platinum (carboplatin AUC 5 or cisplatin 75 mg/m2) + pemetrexed 500 mg/m2, followed by maintenance tislelizumab + pemetrexed (Arm A); pts in Arm B received platinum + pemetrexed and maintenance pemetrexed. Patients with known EGFR mutations or ALK rearrangement were ineligible. Patients were stratified by disease stage (IIIB vs IV) and tumor cell PD-L1 expression (<1% vs 1-49% vs ≥50%) assessed using the Ventana PD-L1 (SP263) Assay. Platinum was administered for 4-6 cycles at investigator's discretion; crossover to tislelizumab was allowed. Treatment beyond progression was allowed for tislelizumab. The primary endpoint, progression-free survival per RECIST v1.1, was assessed by Independent Review Committee (PFSIRC); key secondary endpoints included overall survival (OS), objective response rate (ORRIRC), duration of response (DoRIRC), and safety/tolerability. As of 23 Jan 2020, 334 pts with nsq-NSCLC (A, n=223; B, n=111) were randomized; median study follow-up was 9.8 mo (95% CI: 9.23,10.38). PFSIRC was significantly longer with tislelizumab combination therapy than chemotherapy alone (P=0.0044; HR=0.645 [95% CI: 0.462, 0.902]; median PFSIRC, 9.7 mo vs 7.6 mo). ORRIRC was 57% (95% CI: 50.6, 64.0) and 37% (95% CI: 28.0, 46.6) in Arms A and B, respectively. Median DoR in Arm A was 8.5 mo (95% CI: 6.80, 10.58) and 6.0 mo (95% CI: 4.99, NE) in Arm B. A total of 221 pts (99.5%) had a treatment-related AE (TRAE) in Arm A; 185 pts (83%) had AEs related to tislelizumab. Of 140 pts (63%) with grade ≥3 TRAEs, 69 (31%) were considered related to tislelizumab by the investigator. In Arm B, 107 pts (97%) experienced ≥1 TRAE, of which 50 (46%) were grade ≥3. Across the entire study, four pts (1%) had fatal pneumonitis; 3 of which were considered possibly related to tislelizumab. Tislelizumab plus chemotherapy was generally well tolerated and demonstrated antitumor activity in pts with nsq-NSCLC.