Ono Pharma Files for Approval of Ripretinib (DCC-2618) to Treat Advanced Gastrointestinal Stromal Tumors in Japan
Ono Pharmaceutical Co., Ltd. has announced the submission of a regulatory application in Japan seeking manufacturing and marketing approval for ripretinib (DCC-2618), an investigational therapy developed by Deciphera Ono Pharmaceuticals, Inc.. The application is intended for the treatment of patients with advanced gastrointestinal stromal tumor (GIST) whose disease has progressed following prior cancer therapies, including multiple kinase inhibitors.
This regulatory submission marks a significant milestone in expanding treatment options for patients with advanced GIST in Japan, particularly those who have exhausted currently available therapies. GIST is a rare form of cancer that originates in the connective tissues of the gastrointestinal tract, most commonly in the stomach or small intestine. Although targeted therapies have improved outcomes over the past two decades, many patients eventually develop resistance to treatment, highlighting the need for new therapeutic approaches.
Ripretinib is a switch-control tyrosine kinase inhibitor specifically designed to broadly inhibit KIT and PDGFRA mutations, which are key drivers of GIST. Unlike earlier therapies that target a limited subset of mutations, ripretinib is engineered to provide more comprehensive inhibition across a range of mutation types, including those associated with resistance to prior lines of therapy. This mechanism of action positions ripretinib as a potential option for patients with advanced disease who have limited remaining treatment choices.
The application submitted by Ono is supported by data from the INVICTUS study, a global Phase 3 clinical trial evaluating the efficacy and safety of ripretinib in patients with advanced GIST who had previously been treated with at least three kinase inhibitors, including imatinib. This patient population represents a particularly challenging group, as disease progression following multiple lines of therapy is common and treatment options are limited.
The INVICTUS trial demonstrated that ripretinib significantly improved progression-free survival (PFS), the primary endpoint of the study, compared to placebo. Progression-free survival is a critical measure in oncology trials, reflecting the length of time during which a patient’s disease does not worsen. The Ono Pharma observed benefit in PFS indicates that ripretinib can effectively delay disease progression in heavily pretreated patients, offering a meaningful clinical advantage in this setting.
Beyond its primary endpoint, the study also provided supportive evidence of the drug’s overall clinical benefit, reinforcing its potential role as a later-line therapy for advanced GIST. These findings have already led to regulatory approvals in multiple regions, including the United States and Europe, where ripretinib has been incorporated into treatment guidelines for patients who have progressed on prior therapies.
Despite these global approvals, access to new therapies can sometimes be delayed in certain regions, including Japan, due to differences in regulatory processes and timelines. The submission of this application by Ono represents an important step toward addressing this gap and making ripretinib available to Japanese patients who could benefit from it.
Tatsuya Okamoto, Corporate Officer and Executive Director of Clinical Development at Ono Pharmaceutical, emphasized the importance of this development, noting that GIST is recognized as a rare disease worldwide and that ripretinib has already demonstrated its value in international markets. He highlighted that the application for approval in Japan represents a meaningful advancement for patients and reflects Ono’s ongoing commitment to delivering innovative treatments that address unmet medical needs.
Similarly, Ryota Udagawa, President and Chief Executive Officer of Deciphera, underscored the significance of the submission as a step toward improving patient access. He noted that delays in the availability of new medicines remain a challenge in Japan and expressed optimism that the application could help bring ripretinib to patients more quickly. Udagawa also acknowledged the emotional burden faced by patients with rare cancers such as GIST, where limited information and treatment options can contribute to uncertainty and anxiety.
The collaboration between Ono and Deciphera reflects a strategic partnership aimed at leveraging each company’s strengths to advance the development and commercialization of innovative oncology therapies. While Deciphera has led the global development of ripretinib, Ono is responsible for regulatory submission and commercialization efforts in Japan, ensuring that the therapy is tailored to meet the needs of the local healthcare system.
From a clinical perspective, the introduction of ripretinib into the Japanese market could significantly enhance the treatment landscape for advanced GIST. Current standard therapies, including imatinib, sunitinib, and regorafenib, have improved survival outcomes but are often associated with eventual resistance. As patients progress through these lines of therapy, the availability of additional options becomes increasingly important for maintaining disease control and quality of life.
Ripretinib’s ability to target a broad spectrum of mutations offers a distinct advantage in this context. By addressing both primary and secondary resistance mechanisms, the drug has the potential to extend the duration of disease control in patients who have limited alternatives. Ono Pharma This is particularly relevant for individuals who have already undergone multiple lines of therapy and may have few remaining options.
The submission also highlights the importance of global clinical trials in advancing cancer treatment. The INVICTUS study, conducted across multiple countries, provided robust evidence of ripretinib’s efficacy and safety in a diverse patient population. Such trials are essential for generating the data needed to support regulatory approvals and ensure that new therapies can be made available to patients worldwide.
In addition to its clinical benefits, ripretinib represents a broader trend toward precision medicine in oncology. Ono Pharma By targeting specific molecular drivers of disease, therapies like ripretinib are helping to shift the focus from generalized treatment approaches to more personalized strategies that consider the unique characteristics of each patient’s tumor.
Looking ahead, the review of Ono’s application by Japanese regulatory authorities will be a critical step in determining the timeline for potential approval and commercialization. If approved, ripretinib could become an important addition to the treatment arsenal for advanced GIST in Japan, providing new hope for patients who have exhausted existing options.
The companies involved have expressed a strong commitment to ensuring that patients gain timely access to this therapy. Through continued collaboration and engagement with regulatory authorities, Ono and Deciphera aim to expedite the approval process and bring ripretinib to the Japanese market as quickly as possible.
In conclusion, the submission of the manufacturing and marketing approval application for ripretinib in Japan represents a significant advancement in the treatment of advanced gastrointestinal stromal tumor. Supported by robust clinical data from the INVICTUS trial, the therapy has already demonstrated its potential to improve outcomes for patients with limited treatment options. As the regulatory review process moves forward, the possibility of making this innovative therapy available in Japan offers renewed optimism for patients, clinicians, and the broader oncology community.
About the INVICTUS Study
The INVICTUS Phase 3 clinical study is a randomized, double-blind, placebo-controlled, international, multicenter study conducted in 12 overseas countries including US and EU to evaluate the safety, tolerability, and efficacy of ripretinib compared to placebo in 129 patients with advanced GIST who have received prior treatment with 3 or more kinase inhibitors, including imatinib. Ono Pharma Patients were randomized 2:1 to either 150 mg of ripretinib or placebo once daily.
In the INVICTUS study, ripretinib significantly prolonged the primary endpoint of PFS determined by independent central radiologic review (a median PFS of 6.3 months in ripretinib arm compared to 1.0 month in the placebo arm, HR of 0.15, p<0.0001).1）
About GIST
GIST is a mesenchymal tumor that arises from the muscular layer of the gastrointestinal tract and forms a mass that pushes up the mucosa from below. GIST is a rare disease, with an incidence of approximately 1 to 2 cases per 100,000 population per year. In Japan, the number of patients diagnosed with GIST between 2016 and 2018 was 4,475 over three years (approximately 1,492 cases per year; crude incidence rate: 1.18 cases per 100,000 population).2)
It is known that mutations in KIT (KIT proto-oncogene receptor tyrosine kinase) and PDGFRα (platelet-derived growth factor receptor α) are involved in the development of the majority of patients with GIST. For unresectable, metastatic, or recurrent GIST, four agents—imatinib, sunitinib, regorafenib, and pimitespib—are currently approved in Japan. According to the Japanese clinical practice guidelines for GIST, these agents are recommended as first-line, second-line, third-line, and fourth-line treatments, respectively.3)
About ripretinib
Ripretinib is an orally administered, tyrosine kinase inhibitor developed by Deciphera. Ripretinib inhibits primary and secondary KIT mutations in exons 9, 11, 13, 14, 17, and 18, which are involved in GIST. In addition, ripretinib inhibits primary PDGFRα mutations in exons 12, 14, and 18, including the exon 18 D842V mutation, which is present in a subset of GIST. The INVICTUS study has demonstrated the significant efficacy of ripretinib in patients with advanced GIST who have received prior treatment with 3 or more kinase inhibitors, including imatinib.
Ripretinib was launched in the U.S. in 2020 under the brand name QINLOCK®. As of March 2026, it is approved for the treatment of advanced GIST in more than 40 countries or regions, including the U.S. and European countries. In Japan, ripretinib was designated as an orphan drug by the Ministry of Health, Labour and Welfare on March 19, 2026, for the treatment of GIST that have progressed following cancer chemotherapy. In addition, ripretinib was determined as a drug with high medical needs at the “67th Evaluation Committee on Unapproved or Off-label Drugs with High Medical Needs” held by Ministry of Health, Labour and Welfare, aiming to eliminate drug losses in Japan.
About Deciphera Pharmaceuticals Inc.
Deciphera, a member of Ono Pharmaceutical Co., Ltd., is a biopharmaceutical company focused on discovering, developing, and commercializing important new medicines and providing hope to people living with cancer, neurologic and autoimmune disease. Deciphera is leveraging its proprietary switch-control kinase inhibitor platform and deep expertise in kinase biology to develop a broad portfolio of innovative medicines.
In addition to advancing multiple product candidates from Deciphera’s platform in clinical studies, QINLOCK® (ripretinib) is Deciphera’s switch-control kinase inhibitor approved in many countries including the European Union and the United States for the treatment of adult patients with advanced GIST who have received prior treatment with 3 or more kinase inhibitors, including imatinib.
ROMVIMZA® is a kinase inhibitor approved in the United States for adult patients with symptomatic tenosynovial giant cell tumor (TGCT) for which surgical resection will potentially cause worsening functional limitation or severe morbidity, and in the Ono Pharma European Union for adult patients with TGCT associated with clinically relevant physical function deterioration and in whom surgical options have been exhausted or would induce unacceptable morbidity or disability.
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