Results from the CHOICE-01 phase 3 trial of toripalimab, a humanized monoclonal antibody against PD-1, in combination with first-line chemotherapy for advanced non-small cell lung cancer (NSCLC) were presented at the virtual 2021 World Conference on Lung Cancer.

Patients who were treatment-naïve with advanced NSCLC without EGFR/ALK driver mutations were randomized (2:1) to receive toripalimab 240 mg or placebo in combination with chemotherapy Q3W for 4-6 cycles. Chemotherapy was stratified to paclitaxel plus carboplatin for squamous and pemetrexed plus cisplatin/carboplatin for non-squamous NSCLC.

Following these induction cycles, squamous patients received toripalimab/placebo and non-squamous had toripalimab/placebo in combination with pemetrexed until disease progression, intolerable toxicity, or completion of 2 years of treatment.

“Stratification factors included PD-L1 tumor expression status, histopathology, and smoking status. Crossover to toripalimab was allowed for patients from the placebo arm until disease progression,” explained Jie Wang, MD, PhD, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China, alongside co-investigators.

The primary endpoint was progression-free survival (PFS) with secondary endpoints being overall survival (OS), objective response rate (ORR), and duration of response (DOR), which were reviewed by a blind independent review committee per RECIST v1.1 guidelines.

465 patients with NSCLC (220 squamous and 245 non-squamous) were randomized with 309 to the toripalimab arm and 156 to the placebo arm.

Median follow-up times in both arms were 7.1 and 7.0 months, respectively, with 218 PFS events observed. At the interim analysis, a significant improvement in PFS was shown for toripalimab over placebo (HR=0.58 [95% CI: 0.44-0.77], P=0.0001), with median PFS of 8.3 months versus 5.6 months.

“1-year PFS rates were 32.6% and 13.1%. A significant improvement in PFS was observed in both squamous and non-squamous NSCLC and in PD-L1 expression subgroups. The ORR was 68.7% vs 58.9% for squamous and 58.6% vs 26.5% for non-squamous NSCLC,” continued Dr Wang, et al.

Further, the median DOR was 6.9 vs 4.2 months for squamous and 8.6 vs 5.1 months for non-squamous NSCLC in the toripalimab and placebo arms. OS data was immature, yet a trend was present that favored toripalimab with a median OS rate of 21 vs 16 months (HR=0.81 [95% CI: 0.57-1.17]).

To conclude, these data confirm the addition of toripalimab to standard first-line chemotherapy display superior PFS and ORR with longer DOR than chemotherapy alone with a manageable safety profile in patients with advanced NSCLC.

“These results support the use of toripalimab with chemotherapy as 1^st line therapy for NSCLC patients without driver mutations regardless of histologic subtypes,” concluded Dr Wang, et al. - Alexa Stoia