320MO - Envonalkib vs crizotinib in treatment-naïve advanced ALK-positive NSCLC: A randomized, multicenter, phase III trial

Background

Envonalkib (TQ-B3139, Env) is a novel small molecule ALK/ROS1/c-Met inhibitor. Here, we presented the primary analysis results of a phase III trial, aiming to evaluate the efficacy and safety of Env versus crizotinib (Cri) in advanced ALK-positive NSCLC patients (pts) who had not received a prior ALK inhibitor.

Methods

Eligible pts with ALK-positive and inoperable stage IIIB-IV NSCLC who had not received a prior ALK inhibitor and had received <2 prior lines of chemotherapy were randomized 1:1 to receive Env (600mg, bid, d1-d28) or Cri (250mg, bid, d1-d28) until disease progression or intolerable toxicity. Pts were stratified by baseline brain metastases (present vs. absent) and number of prior chemotherapy lines (0 vs. 1). The primary endpoint was PFS assessed by IRC according to RECIST v1.1. Secondary endpoints included confirmed ORR, DCR, DoR, OS, CNS-ORR, CNS-DoR, CNS-TTP and safety.

Results

From Aug 21, 2019 to Jul 13, 2020, 131 pts were assigned to Env and 133 to Cri. At data cutoff (Oct 14, 2021), the median follow-up was 13.80 m in Env and 10.12 m in Cri. The mPFS by IRC was significantly longer with Env than with Cri (NE vs. 11.89 m; HR 0.46, p < 0.0001). Subgroup analyses of PFS by IRC showed that the efficacy of Env was better than Cri in each subgroup. Confirmed ORR was 81.68% in Env and 69.92% in Cri. Treatment with Env was associated with more durable response (mDoR: NE vs 12.68 m, p=0.0014) than Cri. For pts without BMs at baseline, the incidence of BMs during treatment period in Env significantly lower than that in Cri (1.10% vs 11.83%, p=0.0049). The CNS-ORR in pts with intracranial target lesions at baseline was 78.95% for Env vs. 23.81% for Cri. OS data are immature. Drug-related grade ≥3 TEAEs occurred in 51.91% (Env) vs. 40.60% (Cri). TEAEs led to treatment discontinuation of Env in 4.58% and Cri in 3.01%. Pts with TP53 mutation could also benefit from Env treatment (mPFS: 11.93 vs 7.85 m, HR 0.47). Pts with progressive disease in Env did not develop new insurmountable resistance mutations.

Conclusions

Compared with Cri, Env significantly prolonged PFS in advanced ALK-positive NSCLC pts who had not received a prior ALK inhibitor, and showed greater advantages in controlling BMs. The safety profiles following Env treatment were manageable.

Clinical trial identification

NCT04009317.

Editorial acknowledgement

Legal entity responsible for the study

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Funding

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.