Dupert (fulzerasib)

P1/2, N=334, Completed, Innovent Biologics (Suzhou) Co. Ltd. | Recruiting --> Completed | Trial completion date: Apr 2024 --> Dec 2024

P=N/A, N=200, Not yet recruiting, Cancer Hospital Chinese Academy of Medical Sciences; Cancer Hospital Chinese Academy of Medical Sciences

In targeted therapies, KRASG12C targeted drugs, including Sotorasib, Adagrasib, Fulzerasib, Garsorasib, and Glecirasib, have demonstrated certain therapeutic efficacies in clinical trials and have obtained marketing approval. To tackle drug resistance and enhance patient's prognoses, combination therapeutic strategies that integrate targeted agents with chemotherapy, immune checkpoint inhibitors, Src homology region 2 domain-containing phosphatase 2 (SHP2) inhibitors, and epidermal growth factor receptor (EGFR) monoclonal antibodies have emerged. This paper systematically reviews the advancements in the diagnosis and targeted therapy of NSCLC with KRASG12C mutation, aiming to offer a reference for the selection of clinical treatment regimens and subsequent research..

P=N/A, N=600, Not yet recruiting, Guangdong Association of Clinical Trials

P2, N=48, Not yet recruiting, Guangdong Association of Clinical Trials

The KRAS G12C mutation was once considered "undruggable" until the breakthrough approval of two targeted inhibitors: AMG510 (sotorasib) and MRTX849 (adagrasib). In China, IBI351 and D-1553 have also been approved for the treatment of adult patients with advanced NSCLC harboring the KRAS G12C mutation...Notably, recent findings indicate that combining dual immune checkpoint inhibitors (ICIs; durvalumab and tremelimumab) with chemotherapy (CT) in patients with advanced NSCLC, including those with KRAS mutations, can result in durable survival benefits...Moreover, the POSEIDON trial has highlighted the potential of dual ICI therapy combined with CT to achieve sustained clinical benefits. Despite these advances, the heterogeneity of tumor responses underscores the need for further investigation into intrinsic resistance mechanisms and the strategic optimization of combination therapies to enhance treatment outcomes.

P1/2, N=47, Completed, Genfleet Therapeutics (Shanghai) Inc. | Recruiting --> Completed

P4, N=486, Not yet recruiting, Shanghai Chest Hospital; Shanghai Chest Hospital

No TRAEs resulted in treatment discontinuation. IBI351 demonstrated encouraging clinical efficacy and a manageable safety profile in KRASG12C inhibitor-naïve Chinese patients with KRASG12C-mutated metastatic CRC.

This molecule demonstrates high in vitro potency and selectivity, favorable pharmacokinetic profiles across species, and significant in vivo antitumor efficacy in various cancer-related xenograft models, including intracranial tumors. Fulzerasib has recently received accelerated approval in China for adult NSCLC patients with the KRAS G12C mutation after prior systemic therapy.

Currently, four KRASG12C-specific inhibitors, namely sotorasib, adagrasib, fulzerasib and garsorasib, have garnered regulatory approval. PROTAC-mediated KRAS and SOS1 degradation has been emerged as a promising strategy to overcome these issues, and achieved rapid progress in the recent years. This article provides an overview of the chemical structures, design strategies, structure-activity relationship (SAR) studies as well as in vitro and in vivo activities of the PROTACs degrading KRAS and SOS1, and sheds light on future challenges and opportunities to accelerate the development of new chemotherapies for KRAS-driven cancers.

P2, N=50, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University