Sunvozertinib monotherapy in EGFR tyrosine kinase inhibitor-resistant non-small cell lung cancer with EGFR mutations.

Abstract

Background: Multiple agents can be used to treat patients with EGFR mutated non-small cell lung cancer (NSCLC) who develop resistance to EGFR tyrosine kinase inhibitors (TKIs), but the clinical outcome was not satisfactory, especially in patients with multiple lines of prior therapies. Therefore, there is an unmet medical need for these patients. Sunvozertinib is an oral, potent, irreversible, and mutant-selective EGFR TKI targeting EGFR mutations with weak activity against wild-type EGFR. We investigated the efficacy and safety of sunvozertinib monotherapy in treating EGFR TKI-resistant patients with NSCLC harboring EGFR mutations.

Methods: This was a pooled analysis of phase 1 and 2 studies (WU-KONG1, WU-KONG2 and WU-KONG15). Eligible patients received sunvozertinib at doses ranging from 50 mg to 400 mg once daily. Efficacy endpoints included objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and progression free survival (PFS). Safety endpoints included adverse events and serious adverse events. In addition, plasma specimens were collected at baseline to assess EGFR mutation types and genetic alterations in EGFR downstream signaling pathway.

Results: Forty patients were enrolled. Ninety percent received ≥ 3 prior lines of therapies. The best ORR was 27.5 %, and DCR was 60 %. The median DoR and PFS were 6.5 months and 6 months, respectively. Higher ORR was seen in patients whose last line of treatment was chemotherapy rather than EGFR TKI (31.6 % vs. 14.3 %). Greater responses were seen in patients with EGFR sensitizing and T790M double mutations (ORR: 55.6 %). The safety profile of sunvozertinib was consistent with previous reports.

Conclusions: Sunvozertinib has promising activity implying future investigations in the patients with EGFR mutated NSCLC who developed resistance to prior EGFR TKI.