‘We Have Changed the Practice’: Dr. Yang Presents Final Overall Survival Results From MARIPOSA at ELCC 2025

Amivantamab plus lazertinib is the “first and only treatment to significantly reduce the risk of death” compared with osimertinib in patients receiving first-line treatment for EGFR-mutated advanced non–small cell lung cancer (NSCLC), according to final overall survival (OS) results from the phase 3 MARIPOSA study.

Dr. James Chih-Hsin Yang of the National Taiwan University presented the data at the European Lung Cancer Congress 2025 in Paris, France, during the first proffered paper session of the congress.

“Based on an exponential distribution assumption of overall survival in both arms, the improvement in median overall survival time is projected to exceed 1 year,” Dr. Yang explained as he presented the data showing the OS benefit with amivantamab plus lazertinib versus osimertinib.

The study previously showed that first-line amivantamab plus lazertinib significantly improved progression-free survival (PFS) compared with osimertinib in patients with EGFR-mutated advanced NSCLC (hazard ratio [HR], 0.70; P<0.001), with “consistent benefit across risk groups,” according to the study investigators. In addition, “favorable OS trends were seen” for amivantamab plus lazertinib versus osimertinib at an interim OS analysis.

The study included patients with previously untreated advanced NSCLC with EGFR exon 19 deletions or L858R substitution mutations. Study investigators randomized patients 2:2:1 to receive amivantamab plus lazertinib (n=429), osimertinib (n=429), or lazertinib (n=216). Patients received oral osimertinib 80 mg daily or IV amivantamab 1050 mg (or 1400 mg weekly if they weighed 80 kg or less) weekly for 4 weeks and for every 2 weeks thereafter, plus oral lazertinib 240 mg daily. The OS was “a key secondary end point with type I error rate controlled at 2-sided 5% across interim and final analyses,” according to the study investigators. The protocol-prespecified final OS analysis was conducted when approximately 390 deaths occurred across both arms, he explained.

With a median follow-up of 37.8 months, amivantamab plus lazertinib “demonstrated a statistically significant and clinically meaningful improvement” in OS compared with osimertinib (HR for death, 0.75; 95% CI, 0.61-0.92; P<0.005). The median OS was not estimable in the patients receiving amivantamab plus lazertinib with a 95% CI of 42.9 months to not estimable, compared with a median OS of 36.7 months (95% CI, 33.4-41.0) in patients receiving osimertinib.

“The overall survival for amivantamab plus lazertinib has not reached the median; it was well above 50%. Osimertinib has a median overall survival time of 36.7 months,” Dr. Yang explained. “Over time, you can observe the separation of the Kaplan-Meier curve. It kept widening and widening, and that was manifested at a landmark analysis of 3 years… [showing] 60% of patients on amivantamab plus lazertinib were still alive compared to 51% in the osimertinib arm. And the curves continue to widen.”

Dr. Yang explained that at the 42-month time point, 56% of patients in the amivantamab plus lazertinib arm were still alive and receiving the combination therapy, compared with 44% in those receiving osimertinib.

In addition, the time to symptomatic progression was extended by more than 14 months in patients receiving amivantamab plus lazertinib compared with those receiving osimertinib (43.6 vs 29.3 months; HR, 0.69; 95% CI, 0.57-0.83; nominal P<0.001).

Dr. Yang also explained that data from the study on patients who received subsequent therapies has shown that “there is no prohibition for patients who had received amivantamab plus lazertinib to receive a subsequent treatment.”

In addition, Dr. Yang also highlighted data on central nervous system (CNS) progression and intracranial PFS.

“For these patients, CNS progression is always a concern, and that has contributed to shortened overall survival time and degree and prohibited them from good quality of life,” he explained. “MARIPOSA has a very special design—that patients are mandated to have a brain MRI every 8 weeks for the first 3 years, followed by every 12 weeks subsequently—therefore, we have robust data in the brain MRI to show the intracranial progression-free survival.”

Dr. Yang said that amivantamab plus lazertinib demonstrated a “clinically meaningful improvement in intracranial progression-free survival with a durable response,” with a 36% intracranial PFS rate in the amivantamab plus lazertinib arm, compared with 18% in the osimertinib arm.

He also described the safety results, which were updated and show that “no new signal was found,” and there was “no more than 5% increase in adverse events.” Dr. Yang explained that most adverse events were “related to EGFR and MET inhibition and mostly grade 1 or 2.”

“These are very consistent with what we have found in the primary analysis,” he said. “Of note is that only a minority of patients in this cohort in the MARIPOSA study had received prophylactic treatment, for example, antibody for skin rash or anticoagulation for VTEs [venous thromboembolisms], only 5%.”

Dr. Yang concluded by reflecting on the progress made over the years and how he has seen survival outcomes improve in this population of patients.

“Fifteen years ago, we presented the overall survival data with gefitinib; that was 20 months. And using third-generation osimertinib, we increased the overall survival time to more than 3 years, 38 months. Today, it is my pleasure, we are very delighted to present this data [showing] that by using amivantamab, which is a special bispecific antibody against EGFR and MET, we have changed the practice, [increasing overall survival] from 2 years to 3 years, to now probably more than 4 years,” he said. “With that, all of this could not be accomplished without all of the participants who enrolled in the study, and their family and caregivers. And, of course, all the physicians taking care of them and all the staff members who support this study.”

References

Yang JCH, Kim YJ, Lee SH, et al. Amivantamab plus lazertinib vs osimertinib in first-line (1L) EGFR-mutant (EGFRm) advanced NSCLC: final overall survival (OS) from the phase III MARIPOSA study. Abstract #4O presented at European Lung Cancer Congress 2025, March 26-29; 2025; Paris, France.

Rybrevant® (amivantamab-VMJW) plus Lazcluze^TM (lazertinib) outperforms osimertinib with a significant and unprecedented overall survival benefit in patients with EGFR-mutated non-small cell lung cancer. News release. PR Newswire. March 26, 2025. Accessed March 26, 2025.https://www.prnewswire.com/news-releases/rybrevant-amivantamab-vmjw-plus-lazcluze-lazertinib-outperforms-osimertinib-with-a-significant-and-unprecedented-overall-survival-benefit-in-patients-with-egfr-mutated-non-small-cell-lung-cancer-302412036.html?tc=eml_cleartime

In the photo at top, Dr. James Chih-Hsin Yang of the National Taiwan University presents the MARIPOSA data at the European Lung Cancer Congress 2025 in Paris, France, during the first proffered paper session of the congress. (Photo courtesy of the European Society for Medical Oncology)