Anfangning (garsorasib)

This pooled analysis confirmed the robust efficacy and manageable safety of garsorasib in KRAS G12C-mutated NSCLC.

In this report, we present two patients with advanced PDAC with KRAS G12C mutations who achieved remarkable disease control and prolonged survival following treatment with the KRAS G12C inhibitor D1553 (garsorasib)...Case 2, a 75-year-old woman initially treated with Folinic acid, fluorouracil, irinotecan and oxaliplatin (FOLFIRINOX) and stereotactic body radiotherapy (SBRT), demonstrated sustained disease stability for over three years on KRAS G12C inhibitor therapy...These cases underscore the potential of KRAS-directed therapies in PDAC and illustrate the importance of molecular profiling in identifying eligible patients. The findings support further investigation into the durability of KRAS G12C inhibition, resistance mechanisms, and combination treatment strategies to optimize patient outcomes.

P4, N=104, Not yet recruiting, Shanghai Chest Hospital; Shanghai Chest Hospital

P2, N=30, Not yet recruiting, Shanghai Pulmonary Hospital; Shanghai Pulmonary Hospital

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..

P3, N=400, Not yet recruiting, InxMed (Shanghai) Co., Ltd.

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.

Grade ≥3 treatment-related adverse events occurred in 5 (19.2%) and 6 (14.3%) patients in monotherapy and combination cohort, respectively. Garsorasib with or without cetuximab showed a promising efficacy and manageable safety profiles in heavily pretreated patients with KRAS G12C-mutated CRC, providing a potential new treatment approach for such population.

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.

In this study, we comprehensively evaluate the effectiveness and toxicity of relevant KRAS G12C inhibitors (Sotorasib, Adagrasib, Garsorasib, and Divarasib) in patients with colorectal cancer (CRC), non-small-cell lung cancer (NSCLC), and pancreatic ductal adenocarcinomas (PDAC). However, Adagrasib and Sotorasib are moderately efficient in CRC clinical trials. This study confirms that patients treated with these KRAS G12C inhibitors, exclusively or combined with conventional therapies, achieve better treatment responses and modulate the progressions of these solid tumors.

P1/2, N=92, Active, not recruiting, InventisBio Co., Ltd | Recruiting --> Active, not recruiting

P1/2, N=180, Active, not recruiting, InventisBio Co., Ltd | Trial completion date: Feb 2025 --> Dec 2025