Amivantamab Accolades Add Up for NSCLC

The accolades for amivantamab (Rybrevant; Johnson & Johnson) use against EGFR-mutated non–small cell lung cancer (NSCLC) have been many as of late, with 3 approvals from the FDA this year alone. In March, it was approved for first-line use in patients with EGFR exon 20 insertion mutations based on data from the phase 3 PAPILLON study; in August, as part of a chemotherapy-free first-line regimen with lazertinib (Lazcluze, Janssen Biotech) in patients with exon 19 deletions or exon 21 L858R substitution mutations based on data from the phase MARIPOSA trial; and on September 19, with standard chemotherapy in patients with exon 19 deletions or exon 21 L858R substitution mutations whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) treatment based on data from the phase 3 MARIPOSA-2 trial

Martin Dietrich, MD, PhD, thoracic oncologist with The US Oncology Network and Cancer Care Centers of Brevard in Orlando, Florida, has spoken extensively on amivantamab. Here he discusses the role of EGFR in NSCLC and provides background on the MARIPOSA trial.

This transcript has been lightly edited.

Transcript

Can you provide some background on the role of EGFR within lung cancer?

Well, we know that EGFR played a significant role in non–small cell lung cancer, but it was through the analysis of exceptional responders to the first targeted therapies that we really understood that the EGFR mutations, and not just the presence of the receptor, was critical in obtaining these excellent results. And we've come many generations of drugs in the EGFR-targeting space, with the FLAURA trial with osimertinib in the first-line setting as monotherapy being our standard of care for the last 7 years.

In the last year, we've had the approval of 2 combination therapies, with the most recent approval in MARIPOSA-2, which is a combination therapy of using a third-generation EGFR TKI similar to osimertinib called lazertinib plus a bispecific antibody called amivantamab that targets EGFR and the CMET protein on the extracellular domain at the same time. We've seen some superior progression-free survival in this subset, and this led to the approval of the drug as an additional option in the first-line setting for eligible patients.

What is the current standard of care for patients who have the EGFR mutation?

Up until a year ago, the patients carrying an EGFR exon 19 and exon 21 alteration—at least, the classical alterations—received, almost unanimously, first-line treatment with single-agent osimertinib. This has been augmented. It's still osimertinib—or in this case of discussion of the MARIPOSA trial, lazertinib—have remained the backbone of treatment. It's very good coverage, very high response rate, and also very good coverage of the brain. But the differentiation in the combinations is to flank the efforts of the underlying tyrosine kinase inhibitor with an additional agent that is able to extend the durability, probably by eliminating resistant clones that are the cause of early progression for EGFR targeting with TKIs alone. And they have been proven valuable, especially in high-risk subgroups of brain metastatic disease—for example, visceral disease involvement—and certain genetic coalterations that may be conferring a high-risk phenotype as well.

Can you explain the principal findings of the MARIPOSA trial?

The MARIPOSA trial was a phase 3 prospective randomized study with 3 arms. We had the standard-of-care osimertinib arm, we had a contribution-of-components arm with lazertinib, and the intervention arm that was really used for direct comparison to osimertinib was amivantamab plus lazertinib—so the bispecific antibody that we already had approved in other EGFR indications plus lazertinib here as the comparison. Patients were randomized 2:2:1 between these arms, so lazertinib getting less patients—obviously just to confirm that this is an intrinsic standard that is acceptable—and patients were broadly enrolled with untreated brain metastases carrying EGFR 19 or exon 21 alterations for treatment in the setting, with a primary end point of progression-free survival comparing amivantamab plus lazertinib against standard of care with osimertinib. It was a very large international study that looked at a disease space that has been steady for the last 7 years.