Anti-tumor activity of sunvozertinib in NSCLC with EGFR sensitizing mutations after failure of EGFR TKI treatment

Abstract

BACKGROUND: Sunvozertinib is a rationally designed, irreversible EGFR inhibitor targeting various EGFR mutations with wild-type EGFR selectivity. Clinical studies have showed its superior efficacy than current available therapies and favorable safety profile for treating NSCLC patients with EGFR exon20 mutations. Here we reported its anti-tumor activity in patients with EGFR sensitizing mutations (EGFRm) who failed from standard EGFR TKI treatment. METHODS: This is a pooled analysis of three clinical studies in patients with EGFRm or HER2m NSCLC:WU-KONG1 (multinational phase I/II study, NCT03974022), WU-KONG2 (phase I study in China, CTR20192097), and WU-KONG15 (phase II study in China, NCT05559645). Patients were enrolled to receive sunvozertinib once daily at defined doses until discontinuation criteria were met. Patients who had EGFRm NSCLC, at least one measurable lesion at baseline, received at least one dose of sunvozertinib, and underwent at least one posttreatment RECIST assessment were evaluable for efficacy analysis. Patients with EGFRm or HER2m NSCLC who failed from standard systemic therapies and received at least one dose of sunvoertinib were included in the safety analysis. RESULTS: As of October 17, 2022, a total of 32 patients who met efficacy evaluable criteria were included in the analysis. The doses of sunvozertinib ranged from 50 mg - 400 mg. Baseline characteristics: median age was 64.5 years old; 68.8% (22/32) were female; 75.0% (24/32) ECOG PS was 1; 34.4% (11/32) had more than three metastatic sites; 43.8% (14/32) had baseline brain metastases. Patients were heavily pretreated, with a median of 5 lines (range 1 - 16) of prior therapies. All patients had been treated with at least one type of EGFR TKI, including 68.8% (22/ 32) had been treated with a 3rd generation EGFR TKI. The majority of patients (29/32, 90.6%) had also been treated with chemotherapy. Anti-tumor activity was observed starting from 50 mg. Per investigators' assessment, the best objective response rate (BoR) was 21.9% (7/32). Anti-tumor activity was observed regardless of T790M mutation status. At the data cutoff date, the median duration of response and progression-free survival were 4.0 months and 5.9 months, respectively. Sunvozertinib was well-tolerated across all dose levels. The safety profile was similar to what has been previously reported. The longest treatment duration was more than 35 months (still ongoing). CONCLUSIONS: Sunvozertinib monotherapy demonstrated promising anti-tumor activity in heavily pretreated EGFRm NSCLC patients. Further clinical evaluation of sunvozertinib in this patient population is warranted. The updated data will be presented at the conference.