Kelun-Biotech's Lunbotinib Fumarate Shows Promising Phase II Results in RET Fusion-Positive NSCLC
核心洞察
Lunbotinib fumarate (搜索) demonstrated high objective response rates of 81.3% in treatment-naïve patients and 87.1% in pre-treated patients with RET (搜索) fusion-positive NSCLC.
The next-generation selective RET (搜索) inhibitor showed remarkable intracranial efficacy with a 30% complete response rate in patients with CNS metastases.
The drug exhibited a manageable safety profile with predominantly Grade 1-2 adverse events and only 1.2% permanent discontinuation rate.
Sichuan Kelun-Biotech (搜索) Biopharmaceutical Co., Ltd. presented compelling Phase II data for its next-generation selective RET (搜索) inhibitor, lunbotinib fumarate (搜索) (A400/EP0031), at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting. The pivotal study results in advanced RET fusion-positive non-small cell lung cancer (NSCLC) have led to regulatory acceptance of a New Drug Application (NDA) by China's National Medical Products Administration (NMPA).
Study Design and Patient Population
The Phase II study enrolled 163 patients with RET (搜索) fusion-positive NSCLC, including 71 patients who had previously received platinum-based chemotherapy and immunotherapy (pre-treated patients) and 92 patients who had not received prior systemic therapy (treatment-naïve patients). The median follow-up was 22.6 months for treatment-naïve patients and 20.7 months for pre-treated patients as of the data cutoff date of October 29, 2025.
Efficacy Results
The confirmed objective response rate (ORR) assessed by Independent Review Committee (IRC) reached 81.3% (95% CI: 71.8–88.7) in treatment-naïve patients and 87.1% (95% CI: 77.0–93.9) in pre-treated patients. These response rates demonstrate the drug's efficacy across different treatment lines.
In treatment-naïve patients, both median duration of response (mDOR) and median progression-free survival (mPFS) were not reached, indicating sustained therapeutic benefit. For pre-treated patients, the mDOR was 25.7 months, and mPFS was 27.5 months, showing durable responses even in previously treated populations.
Central Nervous System Efficacy
Among 40 patients with central nervous system (CNS) metastases at baseline, lunbotinib fumarate (搜索) demonstrated notable intracranial activity. The intracranial complete response (CR) rate was 30%, and the disease control rate (DCR) reached 92.5% (95% CI: 79.6–98.4), assessed by IRC per response assessment in neuro-oncology brain metastases (RANO-BM) criteria.
Safety Profile
Lunbotinib fumarate (搜索) was well tolerated across the study population. Treatment-related adverse events (TRAEs) were predominantly Grade 1–2, with a permanent discontinuation rate due to TRAEs of only 1.2%. No treatment-related deaths were reported during the study period.
Clinical Significance
Professor Qing Zhou, principal investigator from Guangdong Provincial People's Hospital, commented on the progression from early-phase studies: "From the first presentation of Phase I data at ASCO 2023 to today's pivotal Phase II results, we have witnessed the progression of lunbotinib fumarate (搜索) from early exploration to a confirmatory study. These data show that lunbotinib fumarate delivers robust and durable responses in both treatment-naïve and pre-treated patients with RET (搜索) fusion-positive NSCLC, with particularly remarkable intracranial efficacy in patients with CNS metastases at baseline."
Regulatory and Development Status
Based on these Phase II results, the NMPA of China has accepted the NDA for lunbotinib fumarate (搜索) for the treatment of adult patients with locally advanced or metastatic RET (搜索) fusion-positive NSCLC. The company is also conducting a Phase Ib/II clinical study in China for RET-positive solid tumors.
Global Development Strategy
Kelun-Biotech (搜索) has established international partnerships for global development. In March 2021, the company granted Ellipses Pharma Limited (搜索) exclusive licensing rights to develop, manufacture and commercialize lunbotinib fumarate (搜索) outside Greater China and certain Asian countries. The FDA cleared the drug for a Phase II clinical trial (NCT05443126) in April 2024, which is currently recruiting patients in the United States, United Kingdom, Europe and United Arab Emirates, evaluating the drug as monotherapy and in combination with chemotherapy.
Lunbotinib fumarate (搜索) represents a novel therapeutic approach for NSCLC, medullary thyroid cancer (MTC) and other solid tumors with RET (搜索) alterations, addressing significant unmet medical needs in oncology treatment.