Non–small-cell lung cancer (NSCLC) with EGFR exon 20 insertion (EGFR exon20ins) mutation is generally refractory to EGFR tyrosine kinase inhibitors and is associated with poor prognosis. Amivantamab (JNJ-61186372) is a novel, fully human anti–EGFR-MET bispecific antibody. Its mechanism of action can target both EGFR- and MET-driven disease. Amivantamab has shown monotherapy activity in patients with EGFR mutant disease characterized by EGFR C797S, T790M, exon20ins, and MET amplification. Preliminary results of an ongoing phase 1 study evaluating amivantamab in patients with advanced NSCLC harboring EGFR exon20ins mutations was presented at the 2020 ASCO Annual Meeting.
The CHRYSALIS study involves a dose-escalation phase in patients with advanced NSCLC and a dose-expansion phase in patients with EGFR- and MET-mutated disease. This analysis of preliminary results includes all patients enrolled with EGFR exon20ins–mutated NSCLC who received the recommended phase 2 dose of 1050 mg (or 1400 mg in patients weighing ≥80 kg). Response was assessed by investigator per Response Evaluation Criteria in Solid Tumors, version 1.1.
As of October 30, 2019, 50 patients with EGFR exon20ins mutations had received amivantamab at the recommended phase 2 dose. Of those, 39 patients were response-evaluable and had 2 or more disease assessments or had discontinued therapy prior to the assessment period. Of the 39 response-evaluable patients, 29 had prior platinum-based chemotherapy. The median age was 61 years (range, 40-78 years), 51% were female, and median prior lines of treatment was 1 (range, 0-7 lines).
Among the 50 patients with EGFR exon20ins mutations who were treated with the recommended phase 2 dose, the most common adverse events reported were rash (72%), infusion-related reaction (60%), and paronychia (34%). Other EGFR-related adverse events included stomatitis (16%), pruritus (14%), and diarrhea (6%). Adverse events of grade ≥3 were reported in 36% of patients. Of these, 6% were treatment-related. One grade 3 incidence of diarrhea was reported, and no rashes of grade ≥3 were reported.
The 39 response-evaluable patients had a median follow-up of 4 months (range, 1-26 months). The overall response rate was 36% (95% confidence interval [CI], 21%-53%). For the 29 patients who had prior platinum-based chemotherapy, the overall response rate was 41% (95% CI, 24%-61%). The clinical benefit rate, as defined by at least partial response or stable disease at ≥11 weeks, was 67% for response-evaluable patients and 72% for patients who had previously received platinum-based chemotherapy.
Among the 14 patients who responded to treatment, the median duration of response was 10 months (range, 1-16 months), with ongoing responses in 9 patients at the time of data cutoff. The median progression-free survival was 8.3 months (95% CI, 3.0-14.8) for response-evaluable patients and 8.6 months (95% CI, 3.7-14.8) for patients who had prior platinum-based chemotherapy.
Based on these preliminary results from the CHRYSALIS study, the investigators conclude that amivantamab demonstrates robust and durable antitumor activity with manageable toxicities in patients with EGFR exon20ins disease.
Source: 2020 ASCO Annual Meeting. Abstract 9512.