Qinlock (ripretinib) / GENESIS Pharma, ZAI Lab, Ono Pharmaceutical, Specialised Therap, Deciphera Pharmaceuticals - LARVOL DELTA

Progression-Free Survival With Second, Third, and Fourth Line Tyrosine Kinase Inhibitors After Imatinib Failure in Gastrointestinal Stromal Tumors: A Genetic Mutation-Stratified Systematic Review and Meta-Analysis (ACG 2026) - "Masitinib did not improve PFS versus sunitinib. In the VOYAGER trial, avapritinib did not improve progression-free survival compared with regorafenib in the overall study population, but it showed activity in patients with PDGFRA D842V mutations... 11 randomized trials including 2,181 patients with advanced gastrointestinal stromal tumors after imatinib failure were included. Overall, active TKIs significantly improved progression-free survival (PFS) compared with placebo or best supportive care (HR 0.32, 95% CI 0.21â0.51) although heterogeneity was substantial. Sunitinib, regorafenib, ripretinib, pazopanib, and imatinib rechallenge showed benefit in delaying disease progression compared with placebo or best supportive care, whereas Nilotinib did not with best supportive care, with or without imatinib or sunitinib."

Retrospective data • Review • Stroma • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

LENVAGIST: A multicentre, comparative, placebo (P)-controlled, double-blinded, phase II study of the efficacy of Lenvatinib (L) in patients with advanced GIST after failure of imatinib and sunitinib (ESMO 2024) - P2 | "Background: In advanced GIST, imatinib, then sunitinib, regorafenib and ripretinib are the usual sequence in 1st, 2nd, 3rd and 4th line, respectively. The LENVAGIST study met its primary endpoint. Lenvatinib leads to clinical benefits in pts presenting advanced GIST after failure of available TKIs."

Clinical • Late-breaking abstract • Metastases • P2 data • Oncology • Solid Tumor • FGFR1 • FLT1 • PDGFRA

From Rapid Progression to Long-Lasting Complete Response: A Wide Range of Ripretinib Activity for Metastatic GIST-A Real-World Cohort. (PubMed, Med Sci (Basel)) - "Durable responses were observed in some patients with KIT exon 11 and secondary exon 17/18 mutations, but this exploratory observation does not establish a predictive molecular subgroup. Larger prospective studies with systematic molecular, radiological, and safety assessment are warranted."

Journal • Real-world evidence • Retrospective data • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • PDGFRA

Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial. (PubMed, J Clin Oncol) - P3 | "Ripretinib was not superior to sunitinib in terms of PFS. However, meaningful clinical activity, fewer grade 3/4 treatment-emergent adverse events, and improved tolerability were observed with ripretinib."

Journal • P3 data • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Solid Tumor

LC-HRMS/MS Characterization of Hydrolytic and Photolytic Degradation Pathways of Ripretinib Following Forced Stress Studies. (PubMed, Rapid Commun Mass Spectrom) - "This investigation elucidates the degradation pathways of ripretinib and highlights the utility of LC-HRMS/MS in the structural characterization of degradation products generated under stress conditions."

Journal • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

Ripretinib versus sunitinib in gastrointestinal stromal tumor: ctDNA biomarker analysis of the phase 3 INTRIGUE trial. (PubMed, Nat Med) - P3 | "INTRIGUE was an open-label, phase 3 study in adult patients with advanced gastrointestinal stromal tumor who had disease progression on or intolerance to imatinib and who were randomized to once-daily ripretinib 150 mg or sunitinib 50 mg. The results of this exploratory analysis suggest ctDNA sequencing may improve the prediction of the efficacy of single-drug therapies and support further evaluation of ripretinib in patients with KIT exon 11 + 17/18 mutations. ClinicalTrials.gov identifier: NCT03673501."

Biomarker • Circulating tumor DNA • Journal • P3 data • Stroma • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT

Efficacy of ripretinib in advanced gastrointestinal stromal tumor and treatment options after resistance: a retrospective real-world study​ (PubMed, Zhonghua Wei Chang Wai Ke Za Zhi) - "After disease progression (PD), the following treatment strategies could be selected after multi-disciplinary team (MDT) (1) the dose of ripretinib was increased from 150 mg once daily to 150 mg twice daily (ripretinib dose-escalation group); (2) The standard-dose ripretinib (150 mg, once daily) was combined with local treatment, including surgery, interventional therapy and radiotherapy (ripretinib combined with local treatment group); (3) standard-dose ripretinib combined with frontline TKI, including imatinib, sunitinib and regorafenib (ripretinib combined with frontline TKI group); (4) other TKI treatment, including imatinib, sunitinib, regorafenib and avapritinib (other TKI treatment group). Ripretinib can serve as an effective treatment option for Chinese patients with advanced GIST after failure of first-line or multiple prior TKI therapies, and it demonstrates a favorable safety profile. Although no standard treatment is currently available for patients with..."

Journal • Real-world evidence • Retrospective data • Cardiovascular • CNS Disorders • Gastrointestinal Stromal Tumor • Hepatology • Oncology • Renal Disease • Sarcoma • Vascular Neurology

Mutational heterogeneity of imatinib resistance and efficacy of ripretinib vs sunitinib in patients with gastrointestinal stromal tumor: ctDNA analysis from INTRIGUE (ASCO Plenary Jan 2023) - P3 | "NCT03673501"

Circulating tumor DNA • Clinical • Heterogeneity • Stroma • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

Updated Overall Survival and Long-Term Safety With Ripretinib Versus Sunitinib in Patients With GI Stromal Tumor: Final Overall Survival Analysis From INTRIGUE. (PubMed, J Clin Oncol) - P3 | "In the INTRIGUE phase III trial (ClinicalTrials.gov identifier: NCT03673501), adult patients with advanced gastrointestinal stromal tumor previously treated with imatinib were randomly assigned 1:1 to ripretinib 150 mg once daily or sunitinib 50 mg once daily (4 weeks on/2 weeks off). Safety was consistent with the primary analysis. OS from this analysis was similar between arms, and second PFS suggests that receiving ripretinib did not adversely affect the PFS of third-line therapy."

Journal • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

Efficacy and Safety of Ripretinib in Chinese Patients with Advanced Gastrointestinal Stromal Tumors as a fourth- or later-line therapy. (PubMed, Clin Cancer Res) - "The results demonstrated that ripretinib can clinically improve the outcomes of Chinese patients with advanced GIST as a fourth- or later-line therapy. The efficacy, safety and pharmacokinetics profiles of ripretinib are consistent with those in the global patient population."

Journal • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

Outcomes in patients with advanced gastrointestinal stromal tumor who did not have baseline ctDNA detected in the INTRIGUE study. (ASCO 2023) - P3 | "Background: Ripretinib is a switch-control tyrosine kinase inhibitor approved for patients (pts) with gastrointestinal stromal tumor (GIST) who received prior treatment with ≥3 kinase inhibitors, including imatinib. Pts with ctDNA-ND had better efficacy outcomes vs pts with ctDNA-D in both treatment arms; PFS was numerically higher with ripretinib vs sunitinib in pts with ctDNA-ND. Although little is known about the biology driving ctDNA in GIST, these data suggest pts may have improved outcomes and different treatment sensitivity based on ctDNA detectability. Clinical trial information: NCT03673501."

Circulating tumor DNA • Clinical • Metastases • Stroma • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

Patient-reported outcomes in individuals with advanced gastrointestinal stromal tumor treated with ripretinib in the fourth-line setting: analysis from the phase 3 INVICTUS trial. (PubMed, BMC Cancer) - P3 | "PRO assessments in the INVICTUS trial suggest that patients on ripretinib maintain their QoL out to C2D1, unlike patients receiving placebo. Longitudinal QoL was maintained for patients receiving ripretinib out to cycle 10, day 1 (approximately 8 months; past the point of median progression-free survival with ripretinib [6.3 months]), even if the patients developed alopecia."

Journal • P3 data • Patient reported outcomes • Alopecia • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • PDGFRA

Updates on Abstract 397784: Mutational Heterogeneity of Imatinib Resistance and Efficacy of Ripretinib Vs Sunitinib in Patients with Gastrointestinal Stromal Tumor: Ctdna Analysis from Intrigue (ASCO 2023) - No abstract available

Circulating tumor DNA • Clinical • Heterogeneity • Stroma • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

Precision therapeutic strategies for advanced gastrointestinal stromal tumors. (PubMed, Cancer Metastasis Rev) - "Imatinib, followed by later-line tyrosine kinase inhibitors, including sunitinib, regorafenib, ripretinib, and genotype-selected avapritinib, have substantially prolonged survival. In this review, we summarize the biological and molecular landscape of advanced GIST, as well as the current therapeutic strategies and major mechanisms of resistance. Finally, we highlight promising therapeutic strategies supported by preclinical and clinical evidence that may advance subtype-informed precision medicine."

Journal • Review • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

Moving beyond a tale of two genes: Strides in management of metastatic gastrointestinal stromal tumors and their supportive care. (PubMed, Am J Health Syst Pharm) - "Studies of the genomic and epigenetic landscape of GISTs have contributed to an understanding of their key molecular features and subsequent therapeutic advances. Supportive care is vital in optimizing treatment outcomes with these novel therapies."

Journal • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • KIT • PDGFRA

Disproportionality analysis of adverse events associated with tyrosine kinase inhibitors in gastrointestinal stromal tumors in the FDA adverse event reporting system. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Imatinib exhibited the most extensive signal spectrum, while Ripretinib has recently surpassed Imatinib in annual reporting volume...Subgroup analyses revealed that males and elderly patients were more prone to hospitalization in patients receiving Ripretinib, whereas younger patients receiving Sunitinib showed a higher likelihood of cardiopulmonary failure. This study delineates distinct safety profiles and temporal risk kinetics for GIST-targeted TKIs. The findings underscore the necessity of intensive early monitoring, particularly for Regorafenib, and suggest that clinical vigilance should be tailored to patient-specific factors to optimize treatment adherence and outcomes."

Adverse events • Journal • Cardiovascular • Dermatology • Endocrine Disorders • Gastrointestinal Stromal Tumor • Hypertension • Oncology • Respiratory Diseases • Sarcoma

Study of DCC-2618 in Patients With GIST After at Least 3 Prior Treatments (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: Ono Pharmaceutical Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

Why precision oncology works: lessons from gastrointestinal stromal tumours. (PubMed, Explor Target Antitumor Ther) - "PDGFRA D842V confers primary resistance to imatinib but sensitivity to avapritinib, illustrating the clinical value of mutation-specific therapy...In advanced disease, sequential use of imatinib, sunitinib, regorafenib, ripretinib, and selected mutation-specific agents reflects evolving resistance biology and the need for ongoing molecular interpretation. Emerging tools such as broader genomic profiling and liquid biopsy may further refine treatment selection. GIST therefore demonstrates that precision oncology is most effective when molecular diagnostics, surgery, systemic therapy, and multidisciplinary decision-making are integrated across the full disease course."

Journal • Review • Oncology • Sarcoma • Solid Tumor • BRAF • NF1 • NTRK • PDGFRA

Keratinocyte Carcinomas Associated with Tyrosine Kinase and Janus Kinase Inhibitors: A Systematic Review (CDA 2026) - "Janus kinase inhibitors accounted for most reported cases, particularly ruxolitinib, followed by tofacitinib and upadacitinib. Tyrosine kinase inhibitors most frequently implicated included sorafenib, imatinib, and ripretinib... Keratinocyte carcinomas have been reported across multiple tyrosine kinase and Janus kinase inhibitors, often occurring early and with significant lesion burden. Janus kinase inhibitors, particularly ruxolitinib, accounted for the largest number of cases and included aggressive outcomes. These findings support proactive dermatologic surveillance and risk counseling for patients initiating these therapies."

Review • Basal Cell Carcinoma • Bowens Disease • Genetic Disorders • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

A phase II study of cabozantinib in metastatic or unresectable refractory gastrointestinal stromal tumour(GIST): a single-centre study from India. (PubMed, BMC Cancer) - "Cabozantinib demonstrated clinically meaningful activity with manageable toxicity in refractory metastatic/advanced GIST after ≥ 3 TKIs, supporting its role as a potential option in LMIC contexts where ripretinib access is limited. Larger, comparative phase III trials are warranted to confirm efficacy and better define optimal patient selection and dosing strategies."

Journal • P2 data • Cardiovascular • Hypertension • Oncology • Sarcoma

Study of DCC-2618 in Patients With GIST After at Least 3 Prior Treatments (clinicaltrials.gov) - P1 | N=10 | Not yet recruiting | Sponsor: Ono Pharmaceutical Co., Ltd.

New P1 trial • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

Ripretinib as preoperative therapy in patients with potentially resectable advanced gastrointestinal stromal tumors after imatinib failure: Final analysis of a prospective, multicenter study. (ASCO 2026) - P=N/A | "After surgery, 6 patients continued ripretinib therapy, while 3 switched to imatinib therapy and 5 switched to sunitinib therapy. These findings demonstrate that preoperative ripretinib effectively reduced tumor burden in patients with imatinib-resistant, potentially resectable advanced GIST, and facilitated successful surgery intervention. Notably, the approach achieved a high NED rate and a low surgical complication rate, supporting ripretinib as a safe and effective preoperative treatment option."

Clinical • Metastases • Stroma • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

Effect of ripretinib on the pharmacokinetics (PK) of repaglinide, a sensitive CYP2C8 probe substrate, in adult patients (pts) with advanced gastrointestinal stromal tumor (GIST). (ASCO 2026) - P1 | "Funded by Deciphera Pharmaceuticals, LLC, a member of ONO Pharma Clinical Trial Registration Number: NCT04530981 Background: Ripretinib is a switch-control tyrosine kinase inhibitor (TKI) indicated for the treatment of adult pts with advanced GIST who have received prior treatment with 3 or more kinase inhibitors, including imatinib. Ripretinib is a weak inhibitor of CYP2C8, with no impact on absorption and a small, clinically insignificant increase in total repaglinide exposure. The safety profile of ripretinib was consistent with its established use in advanced GIST. This study provides the basis for approved concomitant use of ripretinib with CYP2C8 substrates."

Clinical • Metastases • PK/PD data • Stroma • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

Beyond KIT and PDGFRA: Molecular landscape and outcomes of wild-type GIST. (ASCO 2026) - "Imatinib was the most used systemic therapy (n = 14, 77.8%) and first-line in 13 cases; median imatinib duration was 415 days...Subsequent TKIs (sunitinib, regorafenib, ripretinib) and immune checkpoint inhibitors were used in a subset of later-line settings... KIT/PDGFRA WT GIST represents a rare but clinically important subset at our institution, with pronounced molecular heterogeneity driven predominantly by SDH-deficient and RAS pathway–altered tumors and a distinct minority of quadruple WT cases. In this series, long-term survival was unexpectedly favorable despite a high proportion of patients with advanced-stage disease, highlighting the critical role of comprehensive genomic profiling to correctly classify WT GIST. Robust, multi-institutional cohorts are urgently needed to refine prognostic estimates and to develop and test tailored treatment strategies for SDH-deficient and quadruple WT GIST."

IO biomarker • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Solid Tumor • KIT • PDGFRA

Standard-dose ripretinib plus sunitinib versus ripretinib dose escalation in advanced GIST after progression on four prior therapies: Preliminary results of a multicenter cohort study. (ASCO 2026) - "Background: Patients with advanced GIST who progress after four lines of therapy, including imatinib, sunitinib, regorafenib, and ripretinib, face limited treatment options. Preliminary results indicate that ripretinib dose escalation demonstrated superior efficacy and a more favorable safety profile compared with combination therapy involving sunitinib. These findings support ripretinib dose escalation as the preferred treatment option for patients with advanced GIST who have progressed after four lines of standard therapy. However, the sample size in this study is still small, and further research with a larger sample is needed to validate this conclusion."

Clinical • Metastases • Oncology • Sarcoma • Solid Tumor