One year has passed since Leclaza (lazertinib) received FDA approval in combination with Johnson & Johnson’s Rybrevant (amivantamab).

Expanding its influence beyond the United States to Europe and Asia, it has emerged as a global treatment option both in Korea and abroad. In the first half of this year, it recorded an overall survival rate (OS) exceeding 50 months, emerging as a global standard of care for non-small cell lung cancer and contributing to a major shift in the treatment paradigm.

# With the FDA’s decision on whether to approve Rybrevant SC set to be determined in the second half of this year, another 'step-up' is also anticipated for Leclaza, depending on the result.

According to industry sources on the 18th, the FDA approved the use of Rybrevant in combination with Leclaza (US brand name: Lazcluze) as a first-line treatment for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 19 deletion or exon 21 L858R substitution mutation, or adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC).

The combination was also approved in Europe in December of the same year, followed by the UK (March), Japan (March), and Canada (March) in the first quarter of this year, and China (July) in the second quarter.

In May, prescriptions began in Japan, indicating the combination is gaining momentum in its expansion into the global market.

Among the countries that have approved the combination, the combination’s performance in China is particularly noteworthy. With approximately 1 million new lung cancer diagnoses each year, lung cancer is the No.1 cancer in terms of incidence and mortality in China.

This accounts for more than one-third of the 2.5 million new lung cancer cases worldwide. In addition, approximately 85% of lung cancer patients in China have non-small cell lung cancer (EGFR accounts for 40% of non-small cell lung cancer).

Furthermore, the OS results of the Phase III (MARIPOSA) study presented at the European Lung Cancer Congress (ELCC 2025) held in Paris, France, in March this year have further accelerated the growth momentum.

According to the Phase III MARIPOSA study, the combination therapy arm that received Rybrevant and Leclaza saw a 25% reduction in risk of death compared to the Tagrisso (osimertinib, AstraZeneca) arm (HR=0.75, 95% CI: 0.61–0.92, P<0.005). The median overall survival (mOS) in the combination therapy arm has not been reached and was analyzed as NE (95% CI: 42.9–NE), while the Tagrisso arm’s mOS was 36.7 months (95% CI: 33.4–41.0).

This suggests that the use of the combination therapy can add a survival period of over one year when compared to Tagrisso monotherapy.

Based on these results, Yuhan Corp, which successfully licensed out Leclaza, is also achieving financial results in line with the global expansion of Leclaza. The total scale of the licensing out contract for Leclaza that Yuhan Corp signed with Johnson & Johnson in 2018 (including an upfront payment of USD 50 million) was USD 1.255 billion, and following a partial revision of the contract in September last year, the total scale was revised to USD 950 million. The milestone payment alone amounts to USD 900 million.

Yuhan Corp has already received USD 175 million from the amount. Specifically, it received payments for: ▲Combination therapy development (April 2020, USD 35 million) , ▲Initiation of Phase III clinical trials as combination therapy (November 2020, USD 65 million), ▲Initiation of its commercialization in the U.S. (September 2024, USD 60 million), ▲Japan commercialization (May 2025, USD 15 million). The remaining milestone payments total at USD 725 million.

Additionally, the company will receive “royalties on net sales” from global sales of Leclaza separately from the milestone payments. The amount is reported to be over 10% of net sales.J&J currently discloses combined sales of Rybrevant and Leclaza in its quarterly earnings reports. Global sales for the second quarter of this year were USD 179 million, representing a 159% increase from the same period last year and a 27% increase from the previous quarter. Combined sales for the first half of the year, including the first quarter, amounted to USD 320 million.

The pharmaceutical industry believes that the successful expansion of Lecclaza's position in the global market will depend on whether Rybrevant SC, which is currently under review, will be approved by the FDA.

Although inclusion in the NCCN guidelines as the first-line treatment is important, the approval of Rybrevant SC is the biggest variable for the combination’s rapid adoption in clinical practice.

J&J is confident that it will receive FDA approval for Rybrevant SC in the second half of this year based on the PALOMA-3 study, which served as the basis for the application. For reference, the FDA sent a complete response letter (CRL) to J&J regarding Rybrevant SC in December last year.

Jennifer Taubert, Executive Vice President and Worldwide Chairman of Innovative Medicine at Johnson & Johnson, stated, “We have already responded to the FDA's CRL. There were no requests for additional clinical trials or clinical data submissions -- only one or two manufacturing-related questions. We have completed our responses and are hoping to receive approval in the second half of the year.”

Another variable is the OS results of the FLAURA2 Phase III trial on the two-drug regimen of Tagrisso and chemotherapy, which AstraZeneca plans to present at the World Conference on Lung Cancer (WCLC 2025) in September.

The FLAURA2 study enrolled 557 adult patients with EGFR-mutated locally advanced (stage 2B–3C) or metastatic (stage 4) non-small cell lung cancer, and randomized them to receive either Tagrisso 80 mg alone (278 patients) or Tagrisso 80 mg plus Alimta (pemetrexed) plus cisplatin/carboplatin (279 patients).

According to results published in 2023, the primary endpoint, investigator-assessed progression-free survival (PFS), was 25.5 months in the Tagrisso+chemotherapy combination group, extending the median PFS by 8.8 months compared to Tagrisso alone (16.7 months).

An industry insider commented, “When reviewing the FLAURA2 study presented at ESMO Asia last year, of which 60% were Asian patients, the median overall survival (OS) was 40.5 months and 38.3 months, respectively, showing a 2-month improvement as a two-drug regimen. This suggests that a relatively larger OS difference may be observed in non-Asian patients.”

With AstraZeneca announcing statistically significant improvements in OS, a secondary endpoint, attention is now focused on the full OS data from the FLAURA2 study that will be presented at WCLC 2025.

The combination therapy of Rybrevant and Lecclaza, which is indicated as the same line of treatment, has yielded OS data of over 50 months, allowing a direct comparison. The focus is on how much greater OS benefit the Tagrisso-chemotherapy combination therapy can provide relative to the Rybrevant-chemotherapy combination therapy, especially when chemotherapy is administered earlier in the treatment regimen.

This can be a bothersome development for the Rybrevant-Leclaza combination therapy, which is competing for the global preferred regimen position.

The global expansion and scale of achievements for Leclaza could vary significantly depending on the outcome of the Tagrisso-chemotherapy combination therapy OS results and the Rybrevant SC approval.

A representative from Yuhan Corp explained, “Currently, Rybrevant SC has been approved for prescription in Europe, and we are awaiting additional global approvals, including in the United States. The SC formulation reduces the administration time from approximately 6 hours with the existing intravenous (IV) formulation to about 5 minutes, offering various benefits such as improved convenience in administration.”

The representative further noted, “We are also accelerating clinical trials for adverse effect management. J&J presented interim results from a study on reducing the adverse effects of the combination therapy at ASCO 2025. Through preventive skin management, we have reduced adverse events by approximately one-third, and clinical trials are ongoing to further verify its safety in addition to its effect.”