GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, announced the updated results from a registrational phase II trial of Dupert@（fulzerasib）were released in an oral presentation at 2024 World Conference on Lung Cancer (WCLC).
Fulzerasib (GFH925/IBI351) received approval in China on Aug. 21 for the treatment of adult patients with advanced NSCLC harboring KRAS G12C mutation who have received at least one systemic therapy. The first hospital prescription was issued on Aug. 31 and the medications were already shipped to chain pharmacies across the country.
This oral presentation was based on the results from a single-arm phase II clinical study (NCT05005234). The study was led by Professor Yilong Wu and the latest results were presented by Professor Qing Zhou at WCLC. As of the data cutoff date (Dec 13, 2023), a total of 116 NSCLC subjects were enrolled and evaluable. Fulzerasib demonstrated encouraging antitumor activity and was generally well-tolerated with no additional safety signal observed.
The confirmed objective response rate (ORR) assessed by the Independent Radiology Review Committee (IRRC) was 49.1% (95% CI: 39.7-58.6). Disease control rate (DCR) was 90.5% (95%CI: 83.7, 95.2). The median duration of response (DoR) was not reached. Median progression-free survival (PFS) was 9.7 months (95%CI: 5.6-11.0), and median overall survival (OS) was not yet reached.
Treatment-related adverse events (TRAEs) occurred in 107 patients (92.2%) and most were Grade 1-2. The most common TRAEs were anemia, alanine aminotransferase increased, aspartate aminotransferase increased, etc.
Professor Yilong Wu
Guangdong Provincial Hospital
“As a potent KRAS G12C inhibitor, Dupert@ monotherapy has demonstrated encouraging efficacy in advanced lung cancer with KRAS G12C mutations, with the pivotal registry study meeting the prespecified primary endpoints and overall favorable safety profile. As the first KRAS G12C inhibitor approved in China, Dupert@ provides a new treatment option for cancer patients harboring this gene mutation in China. We look forward to seeing more KRAS G12C-mutated patients with advanced lung cancer benefit from this drug soon.”
Yu Wang, M.D.,Ph.D.
Chief Medical Officer of GenFleet
“We are delighted to see the updated results of fulzerasib’s registrational study in the oral presentation at WCLC. We eagerly anticipate a broader patient population benefiting from fulzerasib and look forward to further progress in both monotherapies and combination studies in the future. Currently, GenFleet’s first-line KROCUS study (fulzerasib with cetuximab) is advancing smoothly in a multi-center trial in Europe; in addition to the ongoing G12C inhibitor development, GenFleet’s G12D inhibitor (GFH375) has entered into a phase I/II trial in China. We will be committed to exploring more novel modalities of selective KRAS inhibitors and pan-RAS therapies for patients harboring RAS mutations.”
About Dupert@
（fulzerasib, KRAS G12C Inhibitor)
RAS protein family can be divided into KRAS, HRAS and NRAS categories. KRAS mutation are detected in nearly 90% of pancreatic cancer, 30-40% of colon cancer, and 15-20% lung cancer patients. The occurrence of KRAS G12C mutation subset is more frequently observed than those with ALK, ROS1, RET and NTRK 1/2/3 mutations combined.
Discovered by GenFleet Therapeutics, fulzerasib is a novel, orally active, potent KRAS G12C inhibitor designed to effectively target the GTP/GDP exchange, an essential step in pathway activation, by modifying the cysteine residue of KRAS G12C protein covalently and irreversibly. Preclinical cysteine selectivity studies demonstrated high selectivity of fulzerasib towards G12C. Subsequently, fulzerasib effectively inhibits the downstream signal pathway to induce tumor cells’ apoptosis and cell cycle arrest.
In September 2021, Innovent and GenFleet Therapeutics entered into an exclusive license agreement for the development and commercialization of fulzerasib in China (including the Chinese mainland, Hong Kong, Macau and Taiwan) with additional option-in rights for global development and commercialization.
In January 2023, the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has granted Breakthrough Therapy Designation (BTD) for fulzerasib for the treatment of patients with advanced NSCLC harboring KRAS G12C mutation who have received at least one systemic therapy. In May 2023, the CDE of China’s NMPA granted another BTD for fulzerasib for the treatment of advanced CRC patients with KRAS G12C mutation who have received at least two systemic therapies.
In August 2024, the CDE of NMPA has approved fulzerasib for the treatment of advanced NSCLC patients harboring KRAS G12C mutation who have received at least one systemic therapy.
About GenFleet Therapeutics
GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies, is dedicated to serving significant global unmet medical needs in oncology and immunology. Based on the deep understanding of disease biology and translational medicine, GenFleet’s proprietary and fully integrated R&D platform highlights multiple cutting-edge products with novel mechanisms and global IP.
Since its inception in 2017, GenFleet has built up industry-leading capabilities and expertise in developing novel drug candidates - both small molecules and biologics. Its pipeline includes over 10 programs, many of which have entered later-stage or pivotal clinical trials across China (including Taiwan), the United States, Europe and Australia. Dupert@ (fulzerasib) is the first approved KRAS G12C inhibitor in China and the third globally; it also received NDA priority review designation and two breakthrough therapy designations. Additionally, the first-line combination therapy of fulzerasib and cetuximab has progressed into phase II study in Europe, marking the world's first treatment integrating KRAS and EGFR inhibitors for first-line non-small cell lung cancer.
With accomplished capabilities in developing RAS-pathway targeted therapies, GenFleet's also vigorously pursuing the development of other innovative therapies and novel modalities. Furthermore, it's expanding commercial collaborative network through strategic out-licensing agreements or clinical cooperations with prestigious listed companies including Innovent, Verastem, SELLAS and Merck, BeiGene. GenFleet is expected to progress additional programs into the clinic, as well as transition from a clinical stage biotech company into a commercial stage biopharmaceutical company in the next 3-5 years.
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