The FDA has approved amivantamab-vmjw (Rybrevant®, Janssen) for patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations.
"Despite sharing similar tumor biology to other EGFR-mutant NSCLC tumors, no targeted therapies have been approved for NSCLC harboring EGFR exon 20 insertion mutations," wrote Joshua K. Sabari, MD, medical oncologist at NYU Medical Oncology Associates and colleagues, in the abstract presented in January at the World Conference on Lung Cancer (WCLC). "Amivantamab is a novel, fully human EGFR-MET bispecific antibody with immune cell–directing activity that targets activating and resistance EGFR mutations, as well as MET mutations and amplifications."
Efficacy was evaluated based on data from the phase 1 CHRYSALIS study (NCT02609776), which included 81 patients with NSCLC and EGFR exon 20 insertion mutations whose disease had progressed on or after platinum-based chemotherapy. In this non-randomized, open-label study, patients were treated with amivantamab monotherapy and combination dose escalations in part one, and amivantamab monotherapy and combination dose expansions in part 2. The primary end point was overall response rate, and other end points were duration of response, clinical benefit rate, median progression-free survival, and median overall survival.
At a median follow-up of 6.5 months, the investigator-assessed overall response rate among the 81-patient cohort was 36%, with all patients achieving partial response. The median duration of response was 11.1 months, and 63% of patients had a duration of response of at least 6 months. The clinical benefit rate (at least a partial response or stable disease ≥11 weeks) was 73%, median progression-free survival was 8.3 months, and median overall survival was 22.8 months.
The most common adverse events associated with amivantamab included rash, infusion-related reactions, skin infections around the fingernails or toenails, muscle and joint pain, shortness of breath, nausea, fatigue, swelling in the lower legs or hands or face, sores in the mouth, cough, constipation, vomiting, and changes in certain blood tests.
"Amivantamab treatment led to promising efficacy with durable responses in patients with EGFR exon 20 insertion NSCLC post-platinum doublet and continues to demonstrate a manageable safety profile in over 250 patients treated at the recommended phase 2 dose," concluded Dr. Sabari and colleagues in the WCLC abstract, which was published in the Journal of Thoracic Oncology in March. "A phase 3 study, PAPILLON (NCT04538664), evaluating amivantamab in combination with chemotherapy in the front-line setting is in planning stages."
The recommended dose for amivantamab is 1,050 mg for body weight less than 80 kg, and 1,400 mg for body weight of 80 kg or more, weekly for four weeks, then every 2 weeks thereafter.
For More Information
Sabari JK, Shu CA, Park K, et al (2021). Amivantamab in post-platinum EGFR exon 20 insertion mutant non-small cell lung cancer. J Thorac Oncol (World Conference on Lung Cancer Abstracts), 16(suppl_3):S108-S109. Abstract OA04.04. DOI:10.1016/j.jtho.2021.01.284
Clinicaltrials.gov (2021). A study of combination amivantamab and carboplatin-pemetrexed therapy, compared with carboplatin-pemetrexed, in participants with advanced or metastatic non-small cell lung cancer characterized by epidermal growth factor receptor (EGFR) exon 20 insertions (PAPILLON). NLM identifier: NCT04538664.
US Food & Drug Administration (2021). FDA approves first targeted therapy of subset of non-small cell lung cancer. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-targeted-therapy-subset-non-small-cell-lung-cancer
Image credit: Ventana Medical Systems, Inc. Licensed under CC BY-SA 4.0