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

In vitro profiling of IDRX-42 and NB003 against secondary and tertiary (AP/AL) mutations found in TKI-resistant GIST (AACR 2026) - "Approximately 70-75% of Gastrointestinal stromal tumor (GIST) harbor a KIT mutation and patients with KIT-mutant GIST have durable responses to front-line imatinib (IM)...For example, sunitinib (SU) is potent against AP mutations (V654A, T670I), but has minimal activity against AL mutations. Conversely, ripretinib (RIP) has minimal activity against AP mutations...Ideally, future development of these newer agents should focus on earlier lines of therapy, prior to the development of AP+ AL mutations. The pan-resistance of AP/AL mutations to existing TKIs indicates the need to develop new drugs to target these resistance mutations."

Preclinical • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT

Hair loss in cancer patients receiving small molecule inhibitors: Evidence from clinical trials (AACR 2026) - "Hedgehog pathway inhibitors induced the highest overall rates, ranging from 20-30% with saridegib and glasdegib, and up to 63% with vismodegib. FGFR inhibitors (pemigatinib, infigratinib) and other kinase inhibitors (ripretinib, vemurafenib, sorafenib, AZD0424) demonstrated moderate rates (22-48%). Lower alopecia incidence was reported with aromatase inhibitors (anastrozole, lenostrozole) and the aurora B kinase inhibitor BI 811283, ranging from 9 to 21%...The higher incidences seen with Hedgehog inhibitors, compared with aromatase inhibitors, highlight how pathway-specific disruption of follicular signaling contributes to hair loss. Further research into the molecular mechanisms of these agents may help clinicians better anticipate and manage this side effect."

Clinical • Oncology • BRAF

Ono Pharma Submits an Application for Approval of Ripretinib (DCC-2618) in Patients with Advanced Gastrointestinal Stromal Tumor in Japan (Businesswire) - "This application is based on the results of the INVICTUS study, a global Phase 3 clinical study, evaluating the efficacy of ripretinib compared to placebo in patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib."

Japan filing • Gastrointestinal Stromal Tumor

Benign Keratoses With Inverted Follicular Keratosis-Like Features in a Patient Receiving Ripretinib: A Case Report. (PubMed, J Cutan Pathol) - "Inverted follicular keratosis (IFK) is a rare benign neoplasm of the follicular infundibulum and typically presents as a solitary, nonpigmented verrucous papule on the head and neck of older males and can mimic viral warts, basal cell carcinoma (BCC), or squamous cell carcinoma (SCC). To the best of our knowledge, this represents the first reported association between repretinib treatment and benign keratoses with IFK-like features. Further studies are needed to clarify the clinical significance and biological implications of this observation."

Journal • Actinic Keratosis • Basal Cell Carcinoma • Dermatology • Gastrointestinal Stromal Tumor • Melanoma • Non-melanoma Skin Cancer • Oncology • Sarcoma • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • PDGFRA

A phase I/II study of inlexisertib (DCC-3116) in combination with ripretinib for patients (pts) with advanced gastrointestinal stromal tumor (GIST): Expansion cohort design (Sarcoma-RC 2026) - P1/2 | "In the INTRIGUE trial, the primary endpoint of superior progression-free survival with ripretinib vs sunitinib in second-line (2L) advanced GIST was not met; however, ripretinib showed comparable efficacy and more favorable safety...Trial Design Pts with KIT exon 11–mutant GIST and disease progression on or intolerance to first-line imatinib will be enrolled and treated with inlexisertib 400 mg and ripretinib 150 mg once daily...Legal entity responsible for the study Deciphera Pharmaceuticals, LLC. Funding Deciphera Pharmaceuticals, LLC, a member of ONO Pharma."

Clinical • Combination therapy • Metastases • P1/2 data • Stroma • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • PDGFRA

A phase II study of cabozantinib in metastatic/unresectable refractory GIST from a tertiary care centre in India (Sarcoma-RC 2026) - "Background Ripretinib, the current standard fourth-line therapy in advanced gastrointestinal stromal tumours (GIST), is largely unavailable in LMICs...Legal entity responsible for the study Institute Ethics Committee for Post Graduate Research, all Institute of Medical Sciences, New Delhi, India. Funding Sachin Sarcoma Society."

Metastases • P2 data • Cardiovascular • Hypertension • Sarcoma • Solid Tumor • KDR • KIT

Clinical insights and treatment outcomes of SDH deficient gastrointestinal stromal tumors (GIST): A retrospective analysis from a tertiary care center in India (Sarcoma-RC 2026) - "Response rates were: imatinib, 0% (n=8); sunitinib, 14.3% (2/14); regorafenib, 37.5% (3/8); and temozolomide, 20% (1/5). No responses were noted for cabozantinib (n=2), pemigatinib (n=1), pazopanib (n=1), or ripretinib (n=1); however, one patient had a partial response to doxorubicin...Legal entity responsible for the study The authors. Funding Has not received any funding."

Retrospective data • Stroma • Gastrointestinal Stromal Tumor • Hepatology • Oncology • Sarcoma • SDHB

Time until definitive deterioration (TUDD) in patient-reported outcomes (PROs) with ripretinib vs sunitinib in patients (pts) with advanced gastrointestinal stromal tumor (GIST) previously treated with imatinib who harbor KIT exon 11 + 17/18 mutations: Exploratory analysis from INTRIGUE (Sarcoma-RC 2026) - P3 | "Legal entity responsible for the study Deciphera Pharmaceuticals, LLC. Funding Deciphera Pharmaceuticals, LLC, a member of ONO Pharma."

Clinical • Metastases • Patient reported outcomes • Stroma • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT

External Beam Radiotherapy for Gastrointestinal Stromal Tumor Metastases: A Case Report Demonstrating Long-term Local Control (DKK 2026) - "Case description: A 71-year-old male with metastatic jejunal GIST, diagnosed in 2016, underwent multiple TKI lines (Imatinib 2017-2021, Sunitinib 2021-2023, Regorafenib 2023-2024, and Ripretinib 2024-2025) and radiotherapy for progressive metastases over 9 years. This case suggests that selected GIST metastases may respond favourably to radiotherapy, achieving prolonged local control in TKI resistant patients. These findings warrant further investigation of radiotherapy's role in oligoprogressive GIST and may support its consideration as a local treatment option in multidisciplinary treatment planning. Indication of source: 1."

Case report • Clinical • Stroma • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

Successful treatment of a patient with metastatic gastrointestinal stromal tumor harboring dual KIT exon 9 and 17 mutations with combination of avapritinib, imatinib, and pioglitazone (DKK 2026) - "A relapse occurred in 2018, leading to guideline-based treatment with intermittent administration of sunitinib, regorafenib, and ripretinib...However, this combination caused angiodysplastic bleeding as a side effect, which was managed through off-label bevacizumab treatment...In personalized oncology, traditional trials face challenges with a small number of participants. Moreover, the vast majority of treatments remain unpublished, necessitating the development of new digital AI-supported platforms for collecting real-world data on innovative off-label treatments, thus enabling the development of decision support in personalized oncology for multidisciplinary teams."

Clinical • Metastases • Stroma • Chronic Myeloid Leukemia • Gastrointestinal Stromal Tumor • Hematological Malignancies • Leukemia • Oncology • Sarcoma • HIF1A • KIT

Ripretinib-Induced Focal Segmental Glomerulosclerosis in a Patient With Gastrointestinal Stromal Tumor (GIST). (PubMed, Cureus) - "After four months of prednisone, improvement in proteinuria and serum creatinine was seen. The clinical course suggested that podocyte injuries were induced by ripretinib, the disease process was presumptively responded to steroids, and the podocytopathy lasted after discontinuation of the medication."

Journal • Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Diabetes • Focal Segmental Glomerulosclerosis • Gastrointestinal Stromal Tumor • Glomerulonephritis • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Sarcoma

EGFR/KIT-linked proliferative bias in normal breast lobules from matched non-Hispanic Black and White women is rapidly reversible by RTK inhibition. (PubMed, Am J Pathol) - "Functional plausibility was assessed in pre-stasis human mammary epithelial cells (HMECs) exposed for 24 h to clinically relevant EGFR (lapatinib) or KIT (ripretinib) inhibitors. Together, matched normal tissue and primary-cell data indicate a coordinated EGFR/KIT-linked proliferative bias in NHBW epithelium that is rapidly reversible in vitro. These findings motivate composition-aware validation in larger normal-tissue cohorts and pharmacodynamic window studies to test whether short-term RTK modulation can reset proliferation-biased states in at-risk breast epithelium."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CDK4 • EGFR

Gastrointestinal Stromal Tumors: Molecular Mechanisms of Drug Resistance and Advances in Therapeutic Strategies. (PubMed, J Gastroenterol Hepatol) - "The introduction of imatinib, a selective tyrosine kinase inhibitor (TKI), revolutionized the management of advanced GIST...Current approaches emphasize molecular subtype-guided first-line therapy, ctDNA-driven sequencing of subsequent lines, and the use of novel TKIs (e.g., avapritinib, ripretinib, bezuclastinib) tailored to specific resistance mutations. Furthermore, we explore emerging modalities such as boron neutron capture therapy (BNCT), which offers a kinase-independent mechanism to target resistant disease, and combination strategies that integrate immunotherapy, epigenetic modulators, and pathway-specific inhibitors. Advances in liquid biopsy and molecular profiling are enabling real-time adaptation of therapy, moving GIST management toward a dynamic, personalized paradigm aimed at overcoming resistance and improving patient outcomes."

IO biomarker • Journal • Review • Gastrointestinal Stromal Tumor • Gene Therapies • 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

Gastrointestinal Stromal Tumors: Histopathological Spectrum, Molecular Subtypes, and Implications for Targeted Therapy. (PubMed, Cureus) - "Targeted tyrosine kinase inhibitors (TKIs) have transformed GIST management, with imatinib as the foundational first-line therapy and subsequent agents, sunitinib, regorafenib, avapritinib, and ripretinib, addressing primary or secondary resistance driven by diverse mutational patterns. Emerging therapeutic directions include next-generation kinase inhibitors, heat shock protein inhibitors, immunotherapy, metabolic and epigenetic targeting, and biomarker-driven individualized treatment strategies. This review synthesizes contemporary advances in the histopathological, molecular, and therapeutic landscape of GISTs, emphasizing an integrated diagnostic approach and highlighting ongoing efforts to overcome therapeutic resistance and optimize personalized care."

IO biomarker • Journal • Review • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • ANO1 • BRAF • CD34 • KIT • KRAS • NF1 • NTRK • PDGFRA

INTRIGUE: A Study of Ripretinib vs Sunitinib in Advanced GIST Patients After Treatment With Imatinib (clinicaltrials.gov) - P3 | N=453 | Active, not recruiting | Sponsor: Deciphera Pharmaceuticals, LLC | Trial completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

Outcomes of novel tyrosine kinase inhibitors in rare GIST subtypes: A clinico-genomic analysis from the Flatiron Health–Foundation Medicine database. (ASCO-GI 2026) - "The efficacy of newer TKIs such as regorafenib, ripretinib, and avapritinib in these populations remains poorly described in real-world settings...Use of regorafenib and ripretinib improved outcomes compared with sunitinib alone in SDH-deficient cases (median OS 22.1 vs. 14.2 months, p = 0.03)... In this real-world, genomically annotated cohort, newer TKIs provided clinically meaningful benefit in rare GIST subtypes, particularly SDH-deficient and KIT/PDGFRA wild-type tumors, though outcomes remained inferior to classical KIT/PDGFRA-mutant GIST. These findings support the integration of comprehensive genomic profiling to optimize sequencing of TKIs beyond imatinib in rare GIST populations."

Genomic analysis • Omic analysis • Esophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • KIT • NF1 • PDGFRA

Quantification of buparlisib in human liver microsomes employing an ultra-fast, sensitive UPLC-MS/MS method: in vitro and in silico metabolic stability evaluation. (PubMed, Analyst) - "Ripretinib (RPB) was selected as an internal standard (IS) for BLB quantification in the HLMs matrix. In silico assessments (P450 and DEREK modules) indicate that minor structural changes in the 2-aminopyridine moiety (lability: 58%) and morpholine groups (lability: 42%) during drug design could increase the metabolic stability and safety profile of BLB. The integrated in vitro technique (metabolic incubation) and in silico tools (ADME, DEREK and WhichP450) provide a resource-effective strategy for preliminary metabolic screening and advancing new therapeutic development aimed at enhancing metabolic stability of new BLB derivatives."

Journal • Preclinical

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

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

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

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

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

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