Amivantamab Plus Chemotherapy Approved for Some EGFR-mutated Lung Cancers
Amivantamab with carboplatin and pemetrexed was approved for some advanced non-small cell lung cancers that progressed on or after EGFR inhibition.
The U.S. Food and Drug Administration (FDA) has approved amivantamab-vmjw (Rybrevant) plus the chemotherapeutics carboplatin and pemetrexed for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that harbors certain EGFR mutations (exon 19 deletion or exon 21 L858R substitution) and has progressed during or after treatment with an EGFR inhibitor.
Amivantamab-vmjw is a type of targeted therapy called a bispecific antibody that inhibits both the EGFR and MET proteins. EGFR mutations drive NSCLC by activating cell growth and proliferation, and MET can kickstart these same processes. MET mutations and/or overexpression are common ways tumors develop resistance to EGFR inhibitors, so blocking both proteins together may prevent or overcome treatment resistance.
Amivantamab-vmjw was previously approved for newly diagnosed, EGFR-mutated NSCLC (alone or in combination with either chemotherapy or the EGFR inhibitor lazertinib [Lazcluze]) and for EGFR-mutated NSCLC that progressed after chemotherapy. The latest approval makes it available to patients whose disease progressed after prior EGFR inhibition.
The approval was based on results from MARIPOSA-2, a randomized, open-label, multicenter, phase III clinical trial. The trial enrolled 657 patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations that had progressed on or after treatment with the EGFR inhibitor osimertinib (Tagrisso). Patients were randomly assigned (1:2:2) to receive amivantamab-vmwj with carboplatin and pemetrexed (amivantamab-vmwj + CP arm), carboplatin and pemetrexed (CP arm), or amivantamab-vmwj with other agents.
Treatment responses were observed in 53% and 29% of patients in the amivantamab-vmwj + CP arm and CP arm, respectively. Further, patients in the amivantamab-vmwj + CP arm were 52% less likely than those in the CP arm to experience disease progression or death, with median progression-free survival durations of 6.3 months and 4.2 months, respectively.
The recommended dose for amivantamab-vmwj is based on the patient’s body weight. For patients less than 80 kg, the recommended dose is 1,400 mg weekly for the first four weeks and 1,750 mg every three weeks thereafter. For patients 80 kg or greater, the recommended dose is 1,750 mg weekly for the first four weeks and 2,100 mg every three weeks thereafter.
NSCLC is the most common form of lung cancer, accounting for over 80% of lung cancer cases. Nearly half of EGFR mutations in NSCLC are exon 19 deletions and 35% are L858R mutations. According to federal statistics, it was estimated that 234,580 individuals would be diagnosed with lung cancer and 125,070 patients would die of the disease in the United States in 2024.
The FDA rendered its decision on September 19, 2024.
