Multinational phase 3 trial of first-line sunvozertinib in NSCLC with EGFR exon 20 insertion mutations

Sunvozertinib is an oral EGFR TKI, approved for use in later lines of therapy for patients with advanced non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations. The multinational phase 3 WU-KONG28 trial evaluated sunvozertinib as first-line treatment. A total of 324 patients with advanced nonsquamous NSCLC with exon 20 insertion mutations were randomized to sunvozertinib (n=163) or carboplatin-pemetrexed chemotherapy (n=161). The primary endpoint was progression-free survival as assessed by blinded independent central review. Crossover from chemotherapy to sunvozertinib was allowed after disease progression. Treatment with sunvozertinib led to significantly longer median progression-free survival than chemotherapy (10.3 versus 7.5 months; HR 0.65; p<0.001). The data for overall survival were immature (38.9% maturity). The percentage of patients with an objective response was 58.9% in the sunvozertinib group and 31.1% in the chemotherapy group with median duration of response 11.2 and 7.1 months, respectively. Grade 3 or higher adverse events were reported in 75.5% of patients in the sunvozertinib group and 56.7% of those in the chemotherapy group. No deaths were attributed to adverse events considered to be related to sunvozertinib. The authors conclude that the efficacy of sunvozertinib was superior to that of chemotherapy as first-line treatment for advanced NSCLC with EGFR exon 20 insertion mutations.