Targeted therapy has been around for more than a decade, and now it is becoming more and more popular, and in the field of non-small cell lung cancer treatment, targeted therapy and immunotherapy currently account for half of the country. In the past, targeted therapy was only used for patients with advanced lung cancer, but now targeted adjuvant therapy has entered the treatment guidelines, that is, as long as there is a sensitive gene mutation, intermediate and advanced stage IB lung cancer patients need to use targeted drugs. However, the problem of drug resistance in targeted drugs is also a problem that worries patients and causes headaches for doctors, so scientists continue to develop new drugs to fight drug resistance.
Different from the previous oral small molecule TKI targeted drugs, today's introduction is an antibody targeted drug.
Among the types of lung cancer EGFR mutations, the two classical mutations of exon 19 deletion and 21L858R mutation are the most common, accounting for 90% of lung cancer patients with EGFR mutations, and the rare EGFR exon 20 mutation is more difficult.
In May 2021, the first EGFR/c-Met dual antibody drug approved by the FDA, Rybrevant (amivantamab JNJ-6732), was launched. Evanturumab, a humanized bispecific antibody against EGFR and MET, has the potential to benefit patients with EGFR exon 20 mutation insertion who typically do not respond to currently available oral EGFR-targeted or immune checkpoint inhibitor therapies. At the 2021 ASCO meeting, the second-line treatment of evanturumab was 20ins, os for up to 22.8 months.
As a dual antibody, it is equally effective not only against the target EGFR 20 exon mutation, but also against another target, c-Met. MET mutations are one of the most common rare mutations in lung cancer patients. About 2%-3% of patients with non-small cell lung cancer have MET mutations in the clinic. MET mutations are also seen after EGFR targeted drug resistance, with MET mutations occurring in 5-10% of first- and second-generation EGFR-targeted drug resistance, and 15% of patients with first-line osimertinib resistance developing MET mutations.
At the 2021 Virtual International Association for the Study of Lung Cancer (IASLC) World Lung Cancer Congress (WCLC), data from the NSCLC trial of amivantamab for the treatment of MET exon 14-jump mutations were also updated.
Results showed that the duration of response (DoR) was up to 6.5 months, and in 14 assessable patients, partial response (PR) was observed in 64% and the median time to reach complete response (CR) for the first time was 4.1 months. In addition, antitumor activity was observed in both initial and previously treated patients.
Previous studies have shown that Amivantamab exhibits therapeutic activity for almost all types of EGFR mutations, including EGFR 19del, L858R, T790M, C797S, and 20ins. In addition to showing efficacy in the field of EGFR 20ins and osimertinib resistance, Amivantamab can also be used in the first line to treat EGFR classical mutations. Therefore, amivantamab is also known as a fourth-generation targeted drug. At present, this bispecific antibody has been included in the breakthrough treatment variety of China's State Food and Drug Administration (NMPA) and is carrying out a number of clinical trials in the mainland, including in combination with the third-generation EGFR tyrosine kinase inhibitor razetinib, for the first-line treatment of locally advanced or metastatic non-small cell lung cancer carrying EGFR mutations.
In terms of safety, amivantamab is well tolerated, with a 16% incidence of treatment-related adverse reactions ≥ 3, the most common adverse reactions: rash, infusion reaction (grade 1-2), skin infection around the nail or toenails.
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