Domestic innovation, targeted empowerment: Breakthrough progress in rare lung cancer targets brings new opportunities for lung cancer patients

On November 16, 2023, the National Medical Products Administration (NMPA) released information approving the Class I innovative drug Berrettib Enteric-coated Capsules (trade name: Wanbirui®, Berrettib) independently developed by Beijing Anshi Biotechnology Co., Ltd. (Anshi Biotechnology), a wholly-owned subsidiary of Beijing Purunao Biotechnology Co., Ltd., for the treatment of patients with locally advanced or metastatic non-small cell lung cancer with mesenchymal-epithelial transition factor (MET) exon 14 mutations.

Previously, due to its excellent efficacy and safety, Berretinib was included in the breakthrough therapy drug category by NMPA in February 2021 and included in the priority review and approval process.

MET 14 exon skipping has a poor prognosis in non-small cell lung cancer (NSCLC), which seriously threatens the health of patients and urgently needs better treatment options

Lung cancer is the most common cancer in China, with the highest incidence and mortality rates among all malignant tumors. Non-small cell lung cancer is the main type of lung cancer, among which the proportion of patients with MET 14 exon skipping mutations accounts for 0.9% to 2.0% of all non-small cell lung cancers. The incidence rate is even higher in patients with pulmonary sarcomatoid carcinoma, reaching 13% to 22%. In previous studies, patients with MET 14 exon skipping mutations were older (median age 72.5 years) and prone to brain metastasis (20% to 40%). MET 14 exon skipping mutations are usually associated with high invasiveness, resistance to anti-tumor therapy, and poor prognosis, and chemotherapy and immunotherapy have a poor prognosis.

Several clinical studies have shown that MET inhibitors demonstrate good anti-tumor activity and safety in patients with advanced NSCLC with MET exon 14 skipping. Currently, the efficacy and safety of such drugs are still somewhat different from clinical needs; more effective and safer MET inhibitors remain to be developed.

Barretinib is a highly selective c-MET inhibitor independently developed in my country with excellent activity. Previously, based on the results of a Phase I clinical study announced at the 2020 American Association for Cancer Research (AACR) conference, Barretinib was included in the breakthrough therapy category; this formal approval brings new hope to patients with advanced NSCLC with MET exon 14 mutations.

KUNPENG research lays the foundation for the first-line treatment of NSCLC with MET exon 14 skipping by berretinib

The approval of Berrettinib for the first-line treatment of NSCLC with MET exon 14 skipping is based on the positive results of the KUNPENG study (NCT04258033).

The KUNPENG study is an open, multicenter, single-arm clinical registration phase II study led by Professor Wu Yilong of Guangdong Provincial People's Hospital. As of August 2022, a total of 113 patients were included in the study, of which 52 patients had MET exon 14 mutations. 32.7% (17/52) of the patients had previously received systemic treatment for advanced or metastatic NSCLC; patients received bevacizumab (200 mg, BID) for 28 days per cycle.

The overall objective response rate (ORR) assessed by the blinded independent imaging review committee (BIRC) was 75.0%, the median duration of response (mDoR) was 15.9 months, the median progression-free survival (mPFS) was 14.1 months, and the median overall survival (mOS) was 20.7 months. The ORR for first-time patients was 77.1%, and the ORR for previously treated patients was 70.6%. Patients with brain metastases, liver metastases, and elderly patients (aged ≥ 75 years) of lung cancer can benefit from treatment with bereftib, with ORRs of 100.0%, 66.7%, and 85.7%, respectively. In terms of safety, the overall safety and tolerance are edema, with no potential phototoxicity, hypersensitivity, headache, etc., and the safety risk of combined medication is low.

Professor Yilong Wu, Leading PI of KUNPENG study at Guangdong Provincial People's Hospital, said: "The key registration clinical study of Berretinib showed that ORR reached 75%, mDOR reached 15.9 months, and mOS reached 20.7 months, with clear efficacy and good tolerability. The approval of Berretinib provides a new high-quality treatment option for NSCLC patients with MET exon 14 skipping mutations. In the future, we hope that Berretinib will focus on MET gene abnormalities, target unmet clinical needs, carry out more explorations, and benefit more patients with MET gene abnormalities."

Mr. Hepeng Shi, founder, chairman and CEO of Anshi Biotech, said: "Drug development for MET target-related indications has always been a thorny road. It has been so in the past, is so now, and will probably be so in the future. The approval of Wanbirui® for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping is our first pioneering step in the field of MET target. I believe that the world-class Anshi team will uphold the "tenacity and perseverance" of daring to break through, make full use of the characteristics of Berretinib's strong efficacy, high safety and blood-brain barrier penetration, continue to promote the development of First in Class indications such as glioma, and write a new chapter in the "pan-tumor" treatment of c-MET, benefiting more patients."

As a MET inhibitor independently developed in my country, Berretinib has shown excellent anti-tumor activity in the treatment of NSCLC patients with MET exon 14 mutations, and has good tolerability. The approval of Berretinib will enable more NSCLC patients with MET exon 14 mutations to benefit from precision targeted therapy, bringing new hope of survival to patients. In the future, Berretinib will continue to explore MET gene abnormalities, hoping to bring more breakthroughs to tumor patients with MET mutations in the future.

Note: The content of this article is only for the display of drug marketing information and does not constitute a disease diagnosis or prescription drug recommendation. Anshi Biotechnology does not recommend the use of any unapproved drugs/indications.