A single-arm phase II trial testing a chemotherapy-free combination of the bispecific antibody amivantamab, the third-generation EGFR TKI lazertinib, and the anti-angiogenic agent bevacizumab met its primary endpoint in patients with EGFR-mutant advanced non-small cell lung cancer who had progressed on a third-generation EGFR TKI. The 12-week objective response rate was 33%, with a best overall response of 39%, according to results published in Lancet Respiratory Medicine.
Median duration of response was 13.9 months, progression-free survival was 10.9 months, and updated overall survival was 19.9 months. The investigators say these are among the longest reported in this resistance setting. However, grade 3-4 treatment-related adverse events occurred in 43% of patients, and 20% discontinued treatment due to side effects; infusion-related reactions and acneiform rash were the most common toxicities.
In an accompanying comment, Yun Fan of Zhejiang Cancer Hospital called the efficacy encouraging but pointed to a discordance between the modest objective response rate and the prolonged progression-free survival. She suggested the favorable PFS could reflect enrollment of a lower-risk population, and that the historical benchmark used to power the trial may be outdated. The trial authors themselves note that randomized studies are needed to confirm the findings.