2022年 · 第102卷第13期

Amivantamab (JNJ-61186372) is a fully human EGFR-MET bispecific antibody with immune cell-directing activity designed to provide treatment for patients with non-small cell lung cancer (NSCLC) who have progressed after platinum-containing chemotherapy with insertion mutations in exon 20 of epidermal growth factor receptor (EGFR). A recent phase I, open-label, dose-escalating and dose-expanded "CHRYSALIS" study evaluated the efficacy, safety, and pharmacokinetics of Amivantamab in patients with advanced NSCLC. A total of 362 patients were enrolled in the CHRYSALIS study between May 2016 and June 2020. The recommended dose of 1 050 mg (1 400 mg for patients ≥80 kg) in the Phase II clinical study was determined through the dose escalation phase trial and based on safety, pharmacokinetic and pharmacodynamic data, and 81 patients (effective population) after progression of platinum-containing chemotherapy in the recommended dose group were analyzed centrallyn=81) of the study endpoint assessment. The primary study endpoints were safety and objective response rate (ORR). In terms of safety, the most common adverse reactions were rash (86%), infusion-related reactions (66%), and paronychia (45%). The incidence of grade ≥3 adverse reactions was 35%. The most common grade 3 to 4 adverse reactions were hypokalemia (5%), severe rash (4%), pulmonary embolism, diarrhea, and neutropenia. Of these, 13% of patients underwent treatment-related drug reduction, and 4% discontinued due to adverse reactions. In terms of efficacy, at the time of publication, the median follow-up time of the trial was 9.7 months, and the ORR of the effective population was 40% (32/81). Among the secondary study endpoints, median duration of response (DOR) was 11.1 months, median progression-free survival (PFS) was 8.3 months, and median overall survival (OS) was 22.8 months.

Epidermal growth factor receptor (EGFR) mutation is the most common type of driver gene mutation in non-small cell lung cancer (NSCLC), but current targeted therapy is often more targeted at the classical mutation of EGFR, namely exon 19 deletion and exon 21 L858R mutation. In addition, the third-generation EGFR targeted therapy has a targeted therapeutic effect on patients with T790M mutation. For people with non-classical/uncommon EGFR mutations, such as S768I, L861Q, G719X, etc., there are currently no standard targeted EGFR-tyrosine kinase inhibitor (TKI) treatments by authoritative institutions such as the FDA.