Efficacy and safety of rezivertinib (BPI-7711) in patients with locally advanced or metastatic/recurrent EGFR T790M-mutated NSCLC: A phase IIb, multicenter, singlearm, open-label study.

9098 Background: Rezivertinib (BPI-7711) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) targeting both EGFR-sensitizing mutations and EGFR T790M mutation. This study aimed to evaluate the efficacy and safety of Rezivertinib in patients with locally advanced or metastatic/recurrent EGFR T790M mutated non-small cell lung cancer (NSCLC). Methods: Locally advanced or metastatic/recurrent NSCLC patients with histologic or cytologic or plasmatic confirmation of EGFR T790M mutations who progressed after first/second generation EGFR-TKIs therapy or primary EGFR T790M mutations were enrolled. Patients received Rezivertinib at 180mg orally once daily until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint was objective response rate (ORR) assessed by blinded independent central review (BICR) per RECIST1.1. The efficacy for patients with central nervous system (CNS) metastases was measured by BICR according to the Response Assessment in Neuro-Oncology Brain Metastases. Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. Safety was assessed as per CTCAE 4.03. Results: A total of 226 patients were enrolled from Jul 5, 2019, to Jan 22, 2020. 91 (40.3%) patients had brain metastases. The tissue sample and plasma sample were positive for EGFR T790M in 120 (53.1%) and 116 (51.3%) patients, respectively. By the data cutoff date on Dec 23, 2021, the ORR by BICR was 64.6% (95%CI:58.0-70.8) and DCR was 89.8% (95%CI:85.1-93.4). The median DoR was 12.5 (95%CI:10.0-13.9) months and median PFS was 12.2 (95%CI:9.6-13.9) months. The median OS was 23.9 (95%CI:20.0-NC) months. Subgroup ORR: exon 19 deletion 72.4% (95%CI:64.4-79.5), L858R 51.9% (95%CI:40.4-63.3), tissue T790M positive 70% (95%CI:61.0-78.0), plasma T790M positive 56.9% (95%CI:47.4-66.1). Subgroup PFS: exon 19 deletion 12.4 (95%CI:8.8-15.1) months, L858R 10.3 (95%CI:8.3-13.9) months, tissue T790M positive 13.9 (95%CI:11.3-17.9) months, plasma T790M positive 9.6 (95%CI:7.0-11.0) months. Among 91 patients with CNS metastases, 29 patients had at least one brain target lesion whose CNS-ORR and CNS-DCR were 69.0% (95%CI:49.2-84.7) and 100% (95%CI:88.1-100), respectively. Time to progression of CNS was 16.5 (95%CI:9.7-NC) months. 188 of 226 (83.2%) patients had at least one adverse drug reaction, with the most common being white blood cell count decreased (27.9%), platelet count decreased (23.0%), anemia (22.6%). No interstitial lung disease was reported. Conclusions: Rezivertinib demonstrated promising efficacy and favorable safety for locally advanced or metastatic/recurrent NSCLC patients with EGFR T790M mutation. Clinical trial information: NCT003812809.