Originally published by our sister publication Specialty Pharmacy Continuum

By Gina Shaw
The bispecific antibody amivantamab-vmjw (Rybrevant, Janssen/Johnson & Johnson) plus lazertinib (Lazcluze, Janssen/J&J) significantly extended overall survival (OS) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with certain epidermal growth factor receptor (EGFR) mutations, according to new top-line results from the phase 3 MARIPOSA study.

Improvement in median survival is expected to exceed one year compared with standard-of-care osimertinib (Tagrisso, AstraZeneca), according to the investigators, who added that the study is the first to document OS benefit in EGFR-positive NSCLC over the current standard of care.

Results from the final OS analysis build on previously reported data from the interim analysis and positive results from an analysis of progression-free survival, the primary end point of the randomized phase 3 trial, which enrolled 1,074 patients. That data led to the combination’s approval in August 2024 as a first-line chemotherapy-free treatment for patients with EGFR-mutated advanced lung cancer.

“The combination of these two agents previously demonstrated an improvement in progression-free survival, but this does not always capture the impact on the entire treatment course,” said Stephen Liu, MD, an associate professor of medicine at Georgetown University School of Medicine and the director of thoracic oncology and head of developmental therapeutics at Georgetown Lombardi Comprehensive Cancer Center, in Washington, D.C., in a statement. “Evaluation of overall survival can better demonstrate the benefit of a first-line treatment regimen. Seeing this increase in overall survival in a trial with mature data is powerful.”

Asked to comment on the study, Amanda Cass, PharmD, BCOP, BCPS, a clinical pharmacist specialist of thoracic oncology at Vanderbilt University Medical Center, in Nashville, Tenn., said “it’s always great to see an overall survival benefit. We now have three main options for first-line treatment in this patient population: osimertinib alone, osimertinib plus chemotherapy and amivantamab plus lazertinib. These results mean that this combination will definitely be considered more seriously for first-line treatment.”

Patient preference will play an important role. Osimertinib is a once-daily oral therapy, while the amivantamab- lazertinib combination requires an infusion every two weeks. “Infusion reactions are reported in more than 60% of patients, and in those cases we have to stop the infusion, let the symptoms resolve and then restart the infusion at a half-dose rate,” Dr. Cass said. “This is manageable and we can get patients through it, but it definitely slows down the infusion day. I’ve had most patients take seven to eight hours, if not longer.”

Dr. Cass added that there are strategies for preventing infusion reactions, such as steroids, “but until we have a subcutaneous formulation, this is something we will continue to deal with.” In one recent study comparing IV and subcutaneous amivantamab, fewer patients in the subcutaneous group experienced infusion-related reactions (13% vs. 66%) and venous thromboembolism (9% vs. 14%) versus the IV group (J Clin Oncol 2024;42[30]:3593-3605).

Safety Data

The safety profile of the drug combination was generally consistent with the profiles of the individual treatments, and included venous thromboembolic events. Prophylactic oral anticoagulant therapy has been shown in other studies to significantly reduce the risk for thrombosis (Thromb Res 2014;133[suppl 2]:S122-S127).


An important next step, Dr. Cass said, will be digging further into the clinical trial data to identify subgroups that may benefit from one option versus another. “Does the type of EGFR mutation matter? Is a particular regimen better for patients with a history of brain metastases? There are a lot of things to take into consideration,” she said. “The most important thing is that having that joint discussion so patients can be involved with decision-making about their care.”

J&J has announced that these results will be presented at an upcoming major medical meeting, and will be shared with global health authorities. Amivantamab combined with lazertinib is approved in the United States and Europe for the first-line treatment of patients with EGFR-mutated NSCLC based on the MARIPOSA phase 3 study.