In a phase II trial (WU-KONG1B) reported in the Journal of Clinical Oncology, Yang et al found that the EGFR tyrosine kinase inhibitor sunvozertinib was active at both dose levels tested in patients with platinum-pretreated non–small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations. As stated by the investigators, sunvozertinib is designed to target various EGFR mutations.
Study Details
In the international trial, patients were enrolled between November 2021 and November 2023 and randomly assigned to receive sunvozertinib at 200 mg (n = 91) or 300 mg (n = 93) once daily; after interim analysis, an additional 18 patients were enrolled in the 300-mg group (total = 111 at 300 mg). Overall, 65%, 66%, and 58% of patients in the three groups were Asian. The primary endpoint was confirmed objective response rate on blinded independent review committee assessment, with a null hypothesis of ≤ 17%.
Key Findings
For patients who were evaluable for efficacy, objective response rates were 45.9% (97.5% confidence interval [CI] = 33.6%–58.5%) among 85 in the 200-mg randomized group, 47.2% (97.5% CI = 35.1%–59.5%) among 89 in the 300-mg randomized group, and 45.8% (97.5% CI = 34.8%–57.0%) among 107 in the total 300-mg group. The predefined null hypothesis was rejected with statistical significance (P < .0001).
Compared with the 200-mg randomized group, the 300-mg randomized group had better median duration of response (13.8 months, 95% CI = 8.3 months to not evaluable vs 11.1 months, 95% CI = 8.2 months to not evaluable) and higher objective response rates among patients with baseline brain metastases (21 in each group; 52.4% vs 28.6%) and those with previous amivantamab-vmjw treatment (12 in each group; 41.7% vs 25%).
Grade ≥ 3 treatment-related adverse events occurred in 40.7% of patients in the 200-mg randomized group vs 58.6% of the total 300-mg group; the most common included diarrhea (2.2% vs 18.0%), increased creatine phosphokinase (6.6% vs 12.6%), and anemia (4.4% vs 6.3%).
The investigators concluded: “Sunvozertinib is efficacious at both 200 and 300 mg once daily in treating platinum-pretreated patients with advanced EGFR [exon 20 insertion mutated] NSCLC. The treatment-related adverse events of sunvozertinib were consistent with an EGFR tyrosine kinase inhibitor, with a more favorable safety profile at 200 mg than 300 mg once daily.”
Pasi A. Jänne, MD, PhD, of Dana-Farber Cancer Institute, Boston, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Dizal Pharmaceuticals. For full disclosures of all study authors, visit ascopubs.org.
