"Leclaza, the best first-line option…expanded reimb will increase accessibility"

PALOMA-2 recorded an objective response rate (ORR) of 90 and the 3-year overall survival (OS) rate of 70%…mOS has not yet been reached

Preemptive side effect management strategy added when switching to SC…reducing the burden of administration and management simultaneously

Professor Sun Min Lim, “How long effective treatment can be sustained is important”

Professor Sun Min Lim of the Department of Medical Oncology at Yonsei Cancer Center

What if lung cancer can be managed like a chronic disease? 'Leclaza', a Korea-made new drug for lung cancer, is opening the next chapter of lung cancer treatment. This is because it lowers the treatment burden by switching to subcutaneous (SC) injection, while increasing the likelihood of long-term survival through combination therapy with a bispecific antibody.

Notably, at this year's World Conference on Lung Cancer (WCLC 2026), follow-up studies of the 'Leclaza'-based combination therapy were released, drawing attention to the administration and management strategies that will support long-term treatment. Daily Pharm met with Professor Sun Min Lim of the Department of Medical Oncology at Yonsei Cancer Center at the conference site to hear about the clinical significance of the latest research results and the future direction of treatment.

High efficacy continues even after switching to SC… 'Long-term survival of over 5 years is expected'

At WCLC 2026, held in Seoul from the 12th to the 15th, new research results for the epidermal growth factor receptor (EGFR)-targeted anticancer drug 'Leclaza' (active ingredient: lazertinib) and the bispecific antibody treatment 'Rybrevant' (active ingredient: amivantamab) were disclosed. Receiving the most attention was the phase 2 'PALOMA-2', a study evaluating the combination therapy of 'Leclaza' and 'Rybrevant' SC formulation as a first-line treatment. Results from the phase 2b 'COPERNICUS' study, which added an adverse event prevention strategy to the SC combination therapy, were also presented.

Product photos of Leclaza and Rybrevant

The 31st Korea-made new drug, 'Leclaza', is a third-generation non-small cell lung cancer (NSCLC) treatment targeting EGFR mutations. After Yuhan Corp introduced the candidate substance from Oscotec's subsidiary Genosco in 2015 and developed it, the company out-licensed the global development and commercialization rights to Janssen Biotech, an affiliate of Johnson & Johnson (J&J), in 2018. Since then, Janssen has expanded its global development with combination therapy using its 'Rybrevant', and the 'Leclaza' + 'Rybrevant' combination therapy received approval from the US Food and Drug Administration (FDA) as a first-line treatment for EGFR-mutated NSCLC in August 2024.

Long-term follow-up results from the 'PALOMA-2' study were disclosed this time, and the significance is that this study confirmed long-term treatment effects even with the 'Rybrevant' SC formulation. The 'Leclaza' and 'Rybrevant' SC formulation combination therapy recorded an objective response rate (ORR) of 90% at a median follow-up of 33.1 months, and the median progression-free survival (mPFS) reached 26.1 months. The 3-year progression-free survival (PFS) rate was 37%, and the 3-year overall survival (OS) rate was 70%. The median overall survival (mOS) has not yet been reached.

The existing 'Leclaza' and 'Rybrevant' combination therapy showed a survival benefit in the global phase 3 'MARIPOSA' study, reducing the risk of death by 25% compared with the standard treatment 'Tagrisso' (active ingredient: osimertinib). However, 'Rybrevant' was administered as an IV formulation, and infusion-related reactions (IRR) and long administration times were cited as treatment burdens. The 'PALOMA-2' study broadened the competitiveness of the combination therapy beyond efficacy to administration convenience and sustainability, confirming that high response rates and survival indicators persist even after switching 'Rybrevant' to an SC formulation.

Professor Lim said, "The fact that mOS has not yet been reached means that the patients' survival is continuing for that long," and added, "We are also looking forward to the possibility that it will lead to long-term survival of over 60 months (5 years) in the future."

Professor Lim also added, "Researchers wanted to investigate how much the side effects would decrease by switching to SC,' and, 'As various side effects such as skin rash, as well as infusion-related reactions, showed a numerical decrease compared to the existing MARIPOSA study, it is a combination therapy that can be actively considered in first-line treatment."

Preemptive side effect management, securing treatment adherence… 'patient barriers must be lowered through expanded reimbursement'

The 'COPERNICUS' study, also presented at this conference, showed that the drug increases treatment adherence by adding a preemptive side-effect management strategy when switching to the SC formulation. In 214 patients with advanced NSCLCEGFR-mutant disease and no prior treatment experience, prophylactic anticoagulants and skin adverse-event prevention strategies were used alongside SC 'Rybrevant' + 'Leclaza' combination therapy. At a median follow-up of 8.3 months, skin rash occurred in 25%, and venous thromboembolism (VTE) and administration-related reactions (ARR) occurred in 3% each. Patients who discontinued treatment because of adverse events accounted for 8%, and no patients discontinued treatment because of ARR.

The 'COPERNICUS' study draws attention because it focused on reducing the burden of long-term treatment by combining the SC formulation with a prophylactic management strategy, rather than simply reducing side effects. Professor Lim emphasized, "With the IV formulation, several prophylactic therapies must be added to reduce infusion-related reactions or skin adverse events, but the SC formulation can lower this burden by changing the administration method itself," and added, "Rather than continuously adding prophylactic drugs, treating with SC from the beginning is a more effective approach to reducing the burden on both patients and health professionals."

The switch to SC also offers significant advantages in administration convenience. If 'Rybrevant' is switched to SC, it can be administered in about 5 minutes, without the need to stay in the hospital as long as with the current IV formulation. By shortening administration time, the hospital stay and the medical staff's burden of preparing and administering injections can be reduced. Professor Lim said that in the future treatment of EGFR-mutated lung cancer, competitiveness will depend not only on efficacy but also on how comfortably patients can continue treatment.

Professor Lim considered the 'Leclaza' + 'Rybrevant' combination therapy the most powerful among existing first-line treatment strategies for EGFR-mutated non-small cell lung cancer. Professor Lim said, "If only the treatment effect is considered, the combination therapy would be chosen first as a first-line treatment," and added, "If preemptive and active adverse event management is carried out in the early stages of treatment, patients can stably continue treatment for a long time."

However, accessibility remains a challenge in South Korea. Domestically, 'Leclaza' is reimbursed as a first-line treatment and receives national health insurance coverage, but reimbursement has not yet been applied to the 'Leclaza' + 'Rybrevant' combination therapy. This means that if a patient chooses the combination therapy, they must bear the full cost.

Professor Lim said, "Recently, 'Rybrevant' is expected to receive reimbursement as a treatment for EGFR exon 20 insertion mutations, and the drug price was also adjusted during the reimbursement negotiation process," and added, "If the adjusted drug price is also applied to the first-line combination therapy, it will help lower the financial burden on patients and increase treatment accessibility." Professor Lim continued, "It is necessary to offer reimbursement to pharmaceuticals with clear effects that can extend the survival period, allowing patients to continue effective treatment for a long time."

In the long term, Professor Lim predicted that managing EGFR-mutated lung cancer will also evolve beyond the results of a single treatment into a disease managed through long-term effective treatment. Professor Lim said, "As treatment outcomes continue to improve, EGFR-mutated NSCLC could also come closer to becoming a chronic disease where people live with cancer while managing it long-term, like hypertension or diabetes," and concluded, "In the future, how long effective treatment can be sustained will become even more important."