Zaiping Pharmaceutical's partner Deciphera Pharmaceuticals recently announced that the Food and Drug Administration (FDA) has approved its broad-spectrum KIT and PDGFRα kinase inhibitor Qinlock (ripretinib) for fourth-line treatment of advanced gastrointestinal stromal tumors (GIST ). Qinlock is suitable for adult patients who have previously been treated with 3 or more kinase inhibitors, including: imatinib, sunitinib, regorafenib. In June 2019, Zaiding Pharmaceutical signed an agreement with Deciphera to obtain an exclusive license for the development and promotion of Qinlock in Greater China (Mainland China, Hong Kong, Macau and Taiwan).
It is worth mentioning that Qinlock is the first new drug approved for fourth-line treatment of GIST, which marks an exciting milestone. GIST is a tumor that originates in the gastrointestinal tract, and most patients who initially respond to traditional tyrosine kinase inhibitors will eventually develop tumors due to secondary mutations. In the phase III INVICTUS study, Qinlock showed convincing clinical treatment benefits in terms of progression-free survival (PFS) and overall survival (OS), and had good safety and tolerability. The drug will be four GIST provides a key new therapy.
The approval was three months ahead of the target action date. Qinlock targets a wide range of KIT and PDGFRα mutations, which are known to drive GIST. Previously, the FDA granted Qinlock Breakthrough Drug Qualification (BTD), Fast Track Qualification (FTD), Priority Review Qualification (PRD), and reviewed new drug applications (NDA) under the real-time oncology review (RTOR) pilot program. Qinlock NDA is also part of the Orbis project, an initiative of the Center for Excellence in Oncology (OCE) of the US FDA, which provides a framework for participating international regulatory agencies to simultaneously submit and review oncology drugs.
Richard Pazdur, M.D., director of the FDA Center for Excellence in Oncology and acting director of the Office of Oncology and Diseases at the FDA Center for Drug Evaluation and Research, said: “Despite the progress made in the development of GIST treatments over the past 20 years, including four FDA-approved targeted therapies Methods-Imatinib , Sunitinib , Rigofenib , Avapriny [avapritinib, 2020]-but some patients did not respond to treatment The tumor continues to progress. Today ’s approval provides a new treatment option for patients who have exhausted the FDA approved GIST treatment. "
Qinlock's active pharmaceutical ingredient is ripretinib, which is a KIT / PDGFRα kinase switch regulating inhibitor, used to treat KIT / PDGFRα-driven gastrointestinal stromal tumors (GIST), systemic mastocytosis (SM), and others cancer. Ripretinib is specifically designed to improve the treatment of patients with gastrointestinal stromal tumors by inhibiting the broad-spectrum mutations of KIT and PDGFRα. ripretinib blocks the initial and secondary KIT mutations in exons 9, 11, 13, 14, 17, 18 involved in gastrointestinal stromal tumors and the primary KIT exon 17 found in SM Son D816V mutation. Ripretinib also inhibits primary PDGFRα mutations in exons 12, 14 and 18, including gastrointestinal stromal tumors involving mutations in exon 18 D842V.
In June 2019, Zaiding Pharmaceutical obtained an exclusive license from Deciphera to develop and promote ripretinib in Greater China (Mainland China, Hong Kong, Macau and Taiwan). Under the terms of the agreement, Deciphera will receive a cash advance of US $ 20 million and is eligible to receive up to US $ 185 million in potential development and commercial milestone payments. In addition, Zai Ding Pharmaceuticals will pay Deciphera royalties based on ripretinib's annual net sales in Greater China.
This approval is based on the evaluation of the efficacy data of the key phase III INVICTUS (NCT03353753) study of Qinlock fourth-line treatment of GIST, and the safety data of the INVICTUS and phase I studies. INVICTUS is a randomized (2: 1), double-blind, placebo-controlled study that enrolled 129 patients who had previously received multiple therapies (including at least imatinib, sunitinib, and regofenib) Patients with advanced GIST evaluated the efficacy and safety of Qinlock relative to placebo.
The results published in August 2019 showed that the study reached the primary endpoint: compared with placebo, the progression-free survival was significantly prolonged in the Qinlock treatment group (median PFS: 6.3 months vs 1.0 months), the risk of disease progression or death Significantly reduced by 85% (HR = 0.15, p <0.0001). In terms of secondary endpoint overall survival (OS), the Qinlock treatment group was significantly longer than the placebo group (median OS: 15.1 months vs 6.6 months), and the risk of death was reduced by 64% (HR = 0.36, nominal p = 0.0004 ); It is worth noting that the OS data of the placebo group includes data of patients who turned to Qinlock after the placebo treatment progressed. In terms of the overall secondary response rate (ORR), the Qinlock treatment group significantly increased compared with the placebo group (ORR: 9.4% vs 0%, p = 0.0504).
In terms of safety, the most common adverse reactions (> 20%) are hair loss, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, anorexia, palmoplantar erythrocyte paresthesia syndrome (PPES), and vomiting. Among patients receiving Qinlock, adverse reactions leading to permanent drug withdrawal occurred in 8% of patients, dose interruptions due to adverse reactions occurred in 24% of patients, and dose reductions due to adverse reactions occurred in 7%. Qin Locke treated patients.