Dr Hassan on the CHRYSALIS trial of Amivantamab in EGFR Exon 20–Mutated NSCLC

Khaled Hassan, MD, Khaled Hassan Laboratory, Cleveland Clinic Lerner Research Institute, discusses key results from the phase 1 CHRYSALIS trial (NCT02609776) of the bispecific antibody amivantamab-vmjw (Rybrevant) in non–small cell lung cancer (NSCLC) expressing EGFR exon 20 insertion mutations.

In May 2021, the FDA approved amivantamab for the treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations who had progressed on or following platinum-based chemotherapy. This approval was based on findings from the non-randomized, open-label, dose-escalation and dose-expansion CHRYSALIS trial. The trial’s primary end points for dose escalation and expansion were overall response rate (ORR) and dose-limiting toxicity, Hassan begins. Key secondary end points included duration of response (DOR), clinical benefit rate (CBR), progression-free survival (PFS) and overall survival (OS).

Of the 81 efficacy-evaluable patients, amivantamab elicited an ORR of 40%, Hassan states. This included a complete response rate of 4% and a partial response rate of 36%. The median DOR with amivantamab was 11.1 months. Moreover, around 48% of patients exhibited stable disease, Hassan adds. The PFS and OS with amivantamab were 8.3 months and 22.8 months, respectively. These outcomes were improved compared with other standard of care of agents. Similarly, the CBR was 74% in patients who received the treatment.

The most common adverse effects (AEs) observed with amivantamab were infusion-related reactions, Hassan continues. Accordingly, investigators are attempting to move away from intravenous delivery towards subcutaneous delivery to mitigate these toxicities, Hassan notes. Other AEs included rash, paronychia, musculoskeletal pain, dyspnea, nausea, fatigue, edema, stomatitis, cough, constipation, and vomiting. These are all expected according to known safety signals with other EGFR-targeted therapies, Hassan details. The drug-related discontinuation rate was 4%, although 10% of patients experienced an AE leading to treatment discontinuation, Hassan concludes.