The Rybrevant-Leclaza combination therapy, which has emerged as the standard of care in the field of lung cancer, is set to enter the market in earnest, backed by clinical data.

With three additional indications for EGFR-mutated non-small cell lung cancer added this year, the company plans to leverage its leadership in the field of lung cancer.

On the 22nd, Janssen Korea held a press conference to highlight the indication expansion of Rybrevant (amivantamab) and the clinical value of its combined use with Leclaza (lazertinib).

Results of 3 major Phase III clinical studies of Rybrevant in the treatment of EGFR-mutated non-small cell lung cancer were shared at the conference.

Kihyung Lee, Professor of Hemato-oncology at Chungbuk National University Hospital, who presented at the event, said, “A significant number of patients with EGFR exon 19 deletion and exon 21 (L858R) substitution mutations experience resistance during treatment with existing EGFR-TKIs, with limitations in selecting subsequent treatment options.” He added, “Rybrevant has presented a new treatment method for EGFR-mutated non-small cell lung cancer through the use of combination therapy.”

Rybrevant is the first targeted therapy for EGFR exon 20 insertion mutation non-small cell lung cancer, and it not only targets EGFR exon 20 insertion mutations but also simultaneously targets MET mutations.

Professor Lee said, “Rybrevant inhibits tumor growth and progression by suppressing tumor cells that show not only EGFR mutations but also MET mutations and amplification. It also has a differentiated mechanism of action that induces cancer cell death through immune mechanisms such as natural killer cells and macrophages.”

Rybrevant + Leclaza shows improvement in OS following PFS

The basis for adding the new indication for Rybrevant in EGFR-mutated non-small cell lung cancer was 3 Phase III clinical studies: MARIPOSA-1, MARIPOSA-2, and PAPILLON.

According to the final results of the MARIPOSA Phase III clinical study presented at the European Lung Cancer Congress (ELCC 2025) held in March, showed that the combination therapy of Rybrevant and Leclaza was superior to Tagrisso monotherapy.

The MARIPOSA study is a clinical trial comparing the efficacy and safety of Leclaza + Rybrevant combination therapy with Tagrisso monotherapy, which is currently used as a first-line treatment for EGFR-positive non-small cell lung cancer.

The clinical results showed that the median progression-free survival (PFS) in the Leclaza+Rybrevant group was 23.7 months, which was longer than the 16.6 months recorded in the monotherapy group. In the analysis of overall survival (OS), the secondary endpoint, the Leclaza+Rybrevant group showed a favorable trend compared to the Tagrisso monotherapy group.

Se-Hoon Lee, Professor of Hemato-oncology at Samsung Medical Center, said, “At a median follow-up of 37.8 months, the Rybrevant combination showed a significant improvement in OS compared with osimertinib monotherapy.” He added, “The objective response rate of Rybrevant was 86% in patients with EGFR exon 19 deletion and exon 21 substitution mutations, and the median duration of response was 25.8 months, which means that combination therapy with Rybrevant can be considered a major treatment strategy.”

With Leclaza + Rybrevant confirming its superiority in OS, the EGFR-positive non-small cell lung cancer treatment market is now likely to see combination therapy become the standard treatment.

Currently, this combination therapy has been approved as a first-line treatment in South Korea, the United States, Europe, Japan, the United Kingdom, and Canada.

Particularly, while combination therapy that combines platinum-based chemotherapy with targeted therapy has been approved for EGFR-positive NSCLC in the past, this is the first time a targeted therapy+targeted therapy option has been approved, signifying its significant development.

More options available for EGFR-positive NSCLC, but tailored selection remains a challenge

However, despite the combination rising as a possible standard treatment, there are cost barriers to its immediate use in clinical practice.

With four options now available, including monotherapy and combination therapy, determining the optimal sequence of treatment is also a key consideration.

Professor Lee said, “It is a difficult issue, but with 100 patients that all have different characteristics, I think their conditions must be taken into consideration. Rather than categorizing specific groups, I expect that the most beneficial treatment for each will be selected according to each patient's condition.”

In addition, Janssen Korea expressed its commitment to improving access to combination therapy with Rybrevant.

Yeon-hee Kim, Oncology Business Unit Director at Janssen Korea, added, “We are making various efforts to expand access to Rybrevant combination therapy. We will do our best to ensure that health insurance reimbursement coverage is provided through flexible and active cooperation during the reimbursement review process.”