With the European Lung Cancer Congress (ELCC 2025) just over a month away, industry attention is focused on how the final clinical data from the combination of Leclaza (lazertinib) and Rybrevant (amivantamab) will change the treatment paradigm for EGFR-mutant lung cancer.

According to the industry, final overall survival (OS) data from MARIPOSA, the global phase 3 trial of the Leclaza-Rybrevant combination in patients with EGFR mutation-positive locally advanced or metastatic non-small cell lung cancer (NSCLC), will be presented at the European Society for Lung Cancer Congress in Paris, France, from March 26 to 29.

In January, Johnson & Johnson announced top-line data from the final analysis of the MARIPOSA phase 3 trial, which showed that the Leclaza-Rybrevant combination, a first-line treatment for EGFR-mutant NSCLC, met its secondary endpoint of OS.

According to the announcement, the Leclaza-Rybrevant combination clinically and statistically significantly prolonged OS by more than one year compared to Tagrisso (osimertinib), the current standard of care for first-line treatment.

The median overall survival (mOS) of Tagrisso monotherapy in the FLAURA study, the licensing trial for Tagrisso, was 38.6 months, and the mOS of the Leclaza-Rybrevant combination is expected to extend by 12 months to more than 50 months. That makes the Leclaza-Rybrevant combination the first regimen to show a survival benefit over Tagrisso in first-line treatment.

“The emergence of a treatment option that demonstrates with 12 months longer OS than the standard of care is an important step forward for both physicians and patients,” said Professor Lee Se-hoon of the Department of Hematology-Oncology at Samsung Medical Center. “The Leclaza-Rybrevant combo has shown strong antitumor activity and a manageable and predictable safety profile by combining targeted therapies without toxic chemotherapy. Its use could be even greater if prescription access is secured.”

The Leclaza-Rybrevant combination has already won approval in Korea. On Jan. 13, the Ministry of Food and Drug Safety (MFDS) approved Rybrevant for “combination therapy with lazertinib as first-line treatment for adult patients with locally advanced or metastatic NSCLC harboring EGFR exon 19 deletion or exon 21 (L858R) substitution mutation. That allowed patients in Korea to benefit from this combination therapy.

Some observers believe the OS data for the Leclaza-Rybrevant combination was expected, as Leclaza has shown similar efficacy to Tagrisso as a first-line monotherapy. In the global phase 3 trial (LASER301), Leclaza achieved a median progression-free survival (mPFS) of 20.6 months, compared to 9.7 months for the comparator, first-generation EGFR TKI gefitinib. The results were consistent when analyzing the Korean population separately, with an mPFS of 20.8 months.

“Leclaza is already in the same class and generation as Tagrisso. In global clinical trials, antitumor activity is similar to the standard of care. We expected encouraging OS data because it is combined with the bispecific antibody Rybrevant, which together blocks EGFR and MET receptors and affects antitumor immune function,” said Professor Cho Byoung-chul of the Department of Medical Oncology at Yonsei Cancer Hospital. “The OS data from the MARIPOSA trial could serve as a significant milestone in changing treatment strategies and patterns in the clinic.”