New drug for targeted treatment of gastrointestinal stromal tumors: Ripotinib

Introduction: The American biopharmaceutical company Deciphera reported oral brings hope and improvement to patients with severe gastrointestinal stromal tumor (GIST) who have previously received ≥3 TKIs. It can benefit the progression-free survival and overall survival rate of GIST patients. The patient's risk of disease progression-free or death is reduced by 85%, and the disease-free progression survival is 6.3 months, which is higher than the placebo group (1.0 months).

Pharmacological effects

Reputinib is a TKIs that can inhibit KIT proto-oncogene receptor KIT and platelet-derived PDGFRA kinase, including wild-type, primary and secondary mutations. Ripotinib can inhibit other kinases in vitro, such as PDGFRB, TIE2, VEGFR2 and BRAF genes. Ripotinib binds to the KIT and PDGFRA receptors and to exons 9, 11, 13, 14, 17, and 18 for KIT mutations and exons 12, 14, and 18 for PDGFRA mutations. The "switch pocket" of protein kinases is usually connected to the activation loop and serves as the "switch" of the kinase. Ripotinib has a unique dual mechanism of action that combines the kinase switch pocket and activation loop to shut down the kinase and cause it to cause unregulated tumor cell growth.

Therapeutic Effect

A multi-center, single-arm, open-label phase 2 study designed to evaluate the efficacy, safety and pharmacokinetics (PK) of repotinib as fourth-line or later-line treatment in Chinese patients with advanced GIST. From April 2020 to August 2020, a total of 39 patients were recruited, all of whom were included in the safety analysis, and 38 of them were included in the efficacy analysis. As of February 26, 2021, the median progression-free survival was 7.2 months. The objective response rate was 18.4%. Thirty-seven (94.9%) patients experienced treatment-related adverse reactions. Most adverse reactions are grade 1-2. A total of 6 patients experienced grade 3-4 treatment-related adverse reactions.

Research results

The results of this study show that as a fourth-line or later-line treatment drug, repotinib brings new hope to Chinese patients with advanced gastrointestinal stromal tumors. It has significant curative effect and can effectively improve the prognosis of patients and improve their quality of life. This important discovery provides a new strategy for the treatment of advanced gastrointestinal stromal tumors and is expected to bring good news to more patients.