Innovent Biologics presented updated results from a pivotal Phase 2 clinical trial of fulzerasib (Dupert®) at the 2024 World Conference on Lung Cancer (WCLC), showcasing encouraging antitumor activity and a favorable safety profile in patients with advanced non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation.
Efficacy and Safety Data
The single-arm registrational Phase 2 study (NCT05005234) enrolled 116 NSCLC subjects. As of the data cutoff date (Dec 13, 2023), the confirmed objective response rate (ORR) assessed by the Independent Radiology Review Committee (IRRC) was 49.1% (95% CI: 39.7-58.6). The disease control rate (DCR) reached 90.5% (95%CI: 83.7, 95.2). The median duration of response (DoR) was not yet reached, while the median progression-free survival (PFS) was 9.7 months (95%CI: 5.6-11.0). Median overall survival (OS) has not been reached.
Treatment-related adverse events (TRAEs) occurred in 92.2% of patients (107 individuals), with most events being Grade 1-2. Common TRAEs included anemia, increased alanine aminotransferase, increased aspartate aminotransferase, asthenia, and proteinuria. No new safety signals were observed.
Clinical Significance
Professor Yi-Long Wu from Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, commented, "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."
About Fulzerasib
Fulzerasib is a novel, orally active, and potent KRAS G12C inhibitor designed to target the GTP/GDP exchange by covalently and irreversibly modifying the cysteine residue of the KRAS G12C protein. Preclinical studies have demonstrated high selectivity of fulzerasib towards G12C, leading to inhibition of downstream signaling, resulting in tumor cell apoptosis and cell cycle arrest.
Regulatory Status
In August 2024, fulzerasib received approval from the NMPA in China for the treatment of adult patients with advanced NSCLC harboring the KRAS G12C mutation who have received at least one systemic therapy. The Center for Drug Evaluation (CDE) of China's National Medical Products Administration (NMPA) previously granted Breakthrough Therapy Designation (BTD) to fulzerasib for NSCLC and CRC patients with KRAS G12C mutation.
