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

Treatment research after failure of fourth-line standard therapy for advanced gastrointestinal stromal tumors: A review. (PubMed, Cancer) - "However, some patients develop resistance to imatinib, which leads to accelerated progression, complex genetic mutations, and high spatiotemporal heterogeneity...This article reviews recent research on treatment strategies after the failure of standard treatments for progressive GISTs, including the alternating or combined use of different TKIs, radiotherapy, and immunotherapy. It also discusses relevant advances presented at international conferences, which provide new evidence-based support for clinical decision-making."

IO biomarker • Journal • Review • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

Monitoring the plasma concentration of ripretinib and its metabolites in Chinese patients with gastrointestinal stromal tumors in a real-life setting. (PubMed, Cancer) - "Ripretinib and its metabolites maintained consistent plasma concentrations in Chinese patients with advanced GIST. Furthermore, a trough ripretinib concentration >475 ng/mL was associated with extended survival."

Journal • Alopecia • Dermatology • Fatigue • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Immunology • Oncology • Sarcoma

Long-term outcomes of ripretinib versus sunitinib in Chinese patients with advanced gastrointestinal stromal tumor: An updated analysis of a phase 2 randomized clinical trial. (PubMed, Cancer) - "After two additional years of follow-up, ripretinib showed a trend toward clinically meaningful OS benefit versus sunitinib in the Ex11 ITT population. Second-line ripretinib does not appear to affect third-line treatment efficacy."

Clinical • Journal • P2 data • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

INTEREST: Ripretinib (QINLOCK®) According to Current SmPC (clinicaltrials.gov) - P=N/A | N=10 | Completed | Sponsor: iOMEDICO AG | Recruiting ➔ Completed | N=100 ➔ 10 | Trial completion date: Nov 2027 ➔ Sep 2025 | Trial primary completion date: Sep 2027 ➔ Aug 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

CLINICAL ANALYSIS OF RIPRETINIB DOSE ESCALATION IN ADVANCED GISTS AFTER STANDARD DOSE PROGRESSION (CTOS 2025) - "The other two patient early switched to sunitinib due to lack of response (dose-escalation <=2 months) . Ripretinib dose escalation may offer additional survival benefits with highly individual diversity. The adverse reactions were tolerable, though patient characteristics predicting benefit require further investigation."

Clinical • Metastases • Oncology

INSIGHT: a phase 3, randomized, open-label study of ripretinib vs sunitinib in patients with advanced gastrointestinal stromal tumor with KIT exon 11 + 17/18 mutations who were previously treated with imatinib (DGHO 2025) - P3 | "Pts randomized to the sunitinib arm may cross over to the ripretinib arm upon disease progression. This abstract was originally presented at ASCO 2023."

Clinical • Metastases • P3 data • Stroma • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Solid Tumor

Avapritinib, imatinib and pioglitazone for the treatment of metastatic gastrointestinal stromal tumors (GIST) harboring dual mutations in KIT exons 9/17: a case report (DGHO 2025) - "A relapse occurred in 2018, leading to guideline-based treatment with sunitinib, regorafenib and ripretinib administered intermittently...However, this combination caused angiodysplastic bleeding as a side effect, which was managed through off-label treatment with bevacizumab... In personalized oncology, traditional trials face challenges with small participant numbers and delayed results, highlighting the importance of publishing off-label therapy outcomes as case reports. However, the vast majority of treatments remain unpublished, necessitating the development of new digital AI-supported platforms for collecting real-world data of innovative off-label treatments, thus enabling the development of decision support in personalized oncology for multidisciplinary teams."

Case report • Clinical • Metastases • Stroma • Chronic Myeloid Leukemia • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Hematological Malignancies • Leukemia • Oncology • Sarcoma • HIF1A • KIT

Is there alignment between ESMO-MCBS scores and HTA outcomes for orphan oncology drugs? (ESMO 2025) - "Tebentafusp, with the highest MCBS (score 4), achieved positive HTA outcomes across all markets, whereas ripretinib (score 3), was rejected in the UK due to cost-effectiveness concerns. Lower-scoring drugs (zolbetuximab, pemigatinib, ivosidenib, cabozantinib: score 2) had unfavourable outcomes, including non-quantifiable benefit ratings in Germany, low ASMR ratings in France, and variable outcomes in Spain and the UK. High-scoring drugs avapritinib and irinotecan (score 3), were not consistently reimbursed despite their high scores, while niraparib which achieved a high MCBS (score 3) for both its indications, had consistently unfavourable HTA outcomes across markets...Variability in national HTA methodologies may limit patient access to highly effective therapies, underscoring the need for greater harmonisation to ensure equitable access to orphan oncology drugs across Europe. Legal entity responsible for the study Lane Clark & Peacock LLP."

Oncology • Solid Tumor

Ultra-Fast UPLC-MS/MS Method for the Ripretinib Quantification in the HLMs Matrix With Metabolic Stability Assessment: In-Silico Study for Toxic Alerts and the Metabolic Lability. (PubMed, Arch Pharm (Weinheim)) - "Ripretinib (QINLOCK) is a broad-spectrum, orally-administered, switch-controlled kinase inhibitor that got FDA approval in May 2020 for the treatment of advanced gastrointestinal stromal tumors (GIST) in adult patients who have formerly had treatment with three or more kinase inhibitors, comprising imatinib. In-silico assessments indicate that slight structural changes to the methyl amino group (97%) and the phenylurea moiety (3%) in drug design could increase the metabolic stability of RPB. The evaluation of in-silico RPB ADME characteristics and metabolic stability is fundamental for progressing innovative drug research focused on augmenting metabolic stability."

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

Recent update of treatment using targeted agents in GIST (KINGCA Week 2025) - "Even in the second-line, activities of sunitinib and ripretinib appear to be dependent on secondary mutations, either in ATP-binding or activation loop domain. PDGFRA exon 18 D842V-mutated GIST is highly resistant to imatinib, however, avapritinib demonstrated an excellent ORR (91%) with median PFS of 34.0 months...Dabrafenib plus trametinib is recommended for GIST with BRAF mutations (V600E), and entrectinib and larotrectinib are recommended for GIST with NTRK-fusions. For SDH-GIST, several investigational drugs, including temozolomide, are being evaluated. Among them, rogaratinib, a pan-FGFR inhibitor, appears to be most promising with ORR of 42% and median PFS of 31 months. Right now, there is no recommendation for NF1-associated GIST, but case report and clinical trials for NF1- plexiform neurofibromas may indicate potential activities of selective MEK1/MEK2 inhibitors, such as trametinib and selumetinib, which require future clinical trials. In summary, activities..."

Neurofibromatosis • BRAF • MAP2K2 • NF1 • NTRK • PDGFRA

Cabozantinib Sensitizes NSCLC Cells to Radiation by Inducing Ferroptosis via STAT3/MCL1/BECN1/SLC7A11 Axis Suppression. (PubMed, Cancers (Basel)) - "Cabozantinib enhances the radiosensitization of NSCLC cells through ferroptosis induction mediated by the suppression of the STAT3/MCL1/BECN1/SLC7A11 axis. These findings uncover a novel mechanism linking kinase inhibition to redox imbalance and suggest that the pharmacologic modulation of ferroptosis using multi-target TKIs may represent a rational approach to overcome radioresistance in NSCLC."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AXL • BECN1 • MCL1 • SLC7A11 • STAT3

Metabolite identification of ripretinib by UPLC-ESI-MS/MS: in silico prediction, in vitro metabolism, and stability assessment. (PubMed, Food Chem Toxicol) - "Results highlighted neurotoxicity as a significant concern for RTB and its metabolites, while metabolite 1 exhibited hepatotoxicity and nephrotoxicity. The current study unveils metabolic profiles of RTB and helps to understand the biotransformation products-related toxicity."

Journal • Preclinical • Gastrointestinal Cancer • Oncology • Sarcoma • PDGFRA

Negative outcomes associated with tyrosine kinase inhibitors during management of gastrointestinal stromal tumors: examination of data from the FDA adverse event reporting system. (PubMed, Front Oncol) - "Additionally, several significant signals were found on the preferred term (PT) level, including brain fog with avapritinib (ROR = 27.72), pemphigus (ROR = 30.90) with imatinib, nerve injury (ROR = 25.02) with ripretinib, tough blistering (ROR = 54.96) with sunitinib. These findings enhance the characterization of TKI safety, revealing previously unreported or strongly associated signals and highlighting differences between agents. This evidence contributes to a better understanding of TKI-associated risks in clinical practice."

Adverse events • Journal • Endocrine Disorders • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma

New cancer drugs approved for use for NHS Scotland…zanubrutinib, also known as Brukinsa, was accepted to treat adults with mantle cell lymphoma (Ireland Live) - "The SMC has also approved the drug ripretinib – also known as Qinlock – to treat adults with advanced gastrointestinal stromal tumours, which are a rare type of cancer of the digestive system."

Reimbursement • Gastrointestinal Stromal Tumor • Mantle Cell Lymphoma

A case report of advanced small intestinal stromal tumor with KIT gene mutation and BRCA2 deletion after multi-line treatments. (PubMed, Front Oncol) - "After initial surgery and adjuvant imatinib, the tumor recurred. Through comprehensive analysis of gene mutation profiles (KIT and HRR gene mutations, including BRCA2), a combination therapy of fluzoparib, pamiparib, and ripretinib was administered, stabilizing the patient's condition with significant efficacy. This case highlights the importance of genetic testing and personalized targeted treatment strategies for gastrointestinal stromal tumor (GIST) patients."

Journal • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • BRCA2 • HRD • KIT

Tyrosine Kinase Inhibitors for Gastrointestinal Stromal Tumor After Imatinib Resistance. (PubMed, Pharmaceutics) - "Sunitinib, regorafenib, and ripretinib are currently approved as standard second-, third-, and fourth-line therapies, each demonstrating efficacy against distinct mutational profiles. Avapritinib, notably effective against PDGFRA D842V mutations, represents a milestone for previously untreatable subgroups. Several alternative agents-such as nilotinib, masitinib, sorafenib, dovitinib, pazopanib, and ponatinib-have shown varying degrees of success in refractory cases or specific genotypes. Investigational compounds, including crenolanib, bezuclastinib, famitinib, motesanib, midostaurin, IDRX-42, and olverembatinib, are under development to address resistant or wild-type GISTs...Future strategies include precision medicine approaches such as ctDNA-guided therapy, rational drug combinations, and novel drug delivery systems to optimize bioavailability and reduce toxicity. Ongoing research will be crucial for refining treatment sequencing and expanding therapeutic options,..."

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

Present management of gastrointestinal stromal tumors. (PubMed, Klin Onkol) - "In advanced or metastatic disease, standard care involves sequential treatment with tyrosine kinase inhibitors, including imatinib, sunitinib, and regorafenib. The expanding range of targeted therapies, such as avapritinib for the PDGFRA D842V mutation, underscores the importance of molecular profiling in guiding optimal treatment strategies. This review aims to summarize current knowledge on the diagnosis and treatment of GIST, with a focus on the role of molecular-genetic profiling, the therapeutic value of individual tyrosine kinase inhibitors, and emerging options for advanced disease, with particular emphasis on ripretinib."

Journal • Review • Chronic Myeloid Leukemia • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Hematological Malignancies • Leukemia • Oncology • Sarcoma • PDGFRA

Ripretinib-related pyoderma gangrenosum: first description and pathophysiological clues. (PubMed, Ann Dermatol Venereol) - No abstract available

Journal • Pyoderma Gangrenosum

Development and Validation of a LC-MS/MS Method for Ripretinib and Its Metabolite: Example of a Journey From Laboratory Bench to Routine Application With a Greenness Assessment. (PubMed, Biomed Chromatogr) - "The greenness assessment score of this procedure was better than previously published approaches using the AGREE metric. The validated UPLC-MS/MS method successfully monitored ripretinib and its metabolite concentrations in clinical and preclinical models."

Journal

Design, synthesis and biological evaluation of novel platelet-derived growth factor receptor-α (PDGFR-α) inhibitors based on 4-anilinoquinoline and 4-anilinoquinazoline scaffolds. (PubMed, Eur J Med Chem) - "Novel 4-anilinoquinoline and 4-anilinoquinazoline hybrids were designed and synthesized as PDGFR-α inhibitors based on lenvatinib, ripretinib and sorafenib. Furthermore, molecular docking results showed that 6o could stably bind to the ATP site of PDGFR-α rationalizing their potent anti-PDGFR-α activity. Based on the above findings, compound 6o could be considered an effective anti-angiogenesis candidate."

Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • PDGFRA

Pharmacokinetics and Safety of Ripretinib in Participants with Hepatic Impairment: A Phase 1 Study. (PubMed, Adv Ther) - "On the basis of the known safety profile of ripretinib, these increased ripretinib and combined ripretinib + DP-5439 exposures in participants with hepatic impairment are unlikely to be clinically relevant. Therefore, no dose adjustments are recommended for patients with gastrointestinal stromal tumor and hepatic impairment."

Journal • P1 data • PK/PD data • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Hepatocellular Cancer • Hepatology • Oncology • Sarcoma • PDGFRA

Cerebral Metastasis of a Gastrointestinal Stromal Tumor: A Case Report and Literature Review. (PubMed, Cureus) - "We report a case of a 58-year-old male with metastatic gastric GIST, treated with imatinib, followed by sunitinib and regorafenib, between October 2021 and December 2023, when he presented with sudden visual disturbances and a transient loss of consciousness...This case underscores the absence of effective systemic treatments for CNS disease, as most TKIs, including imatinib and ripretinib, have poor CNS penetration...This case highlights the need for novel therapeutic approaches targeting CNS metastases and further exploration of molecular mechanisms that enable atypical metastatic spread. This report contributes to the sparse literature on CNS involvement in GIST, emphasizing the need for a multidisciplinary approach and the development of therapies that can penetrate the blood-brain barrier (BBB) to improve outcomes in patients with advanced GIST."

Journal • CNS Disorders • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • PDGFRA

Gastrointestinal stromal tumors with the use of ripretinib and sunitinib: real-world adverse event analysis based on the FDA adverse event reporting system (FAERS). (PubMed, Front Pharmacol) - "This study validated known AEs and identified new potential safety signals associated with ripretinib and sunitinib in GIST treatment. These findings contribute to the understanding of ripretinib and sunitinib, providing valuable evidence for improving its clinical use."

Adverse events • Journal • Real-world evidence • Review • Dermatology • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Genito-urinary Cancer • Kidney Cancer • Oncology • Pain • Renal Cell Carcinoma • Salivary Gland Cancer • Sarcoma • Solid Tumor

Prognostic factors for metastatic gastrointestinal stromal tumors treated with cytoreductive surgery: A retrospective cohort study (ESMO-GI 2025) - "The TKIs used at time of surgery were imatinib (n=53, 72.6%) and subsequent-line TKIs [sunitinib (n=16, 22%), regorafenib (n=2, 2.7%) and ripretinib (n=2, 2.7%)]. Overall, non-MP, R0/1 resection and mitotic index<5/50 HPFs may predict better outcomes for metastatic GISTs undergoing CRS on imatinib and the CRS is feasible and safe."

Biomarker • Metastases • Retrospective data • Stroma • Surgery • Gastrointestinal Cancer • Oncology

Gastrointestinal stromal tumors with the use of ripretinib and sunitinib: real-world adverse event analysis based on the FDA adverse event reporting system (FAERS) (Front Pharmacol) - "A total of 3,636 and 34,768 ADE reports related to ripretinib and sunitinib were identified using four disproportionality analysis methods. The top five ADR signals for ripretinib include hepatic embolization, tumor compression, hyperkeratosis, tumor excision and tumor pain. For sunitinib, the five strongest ADR signals are metastatic renal cell carcinoma, diffuse uveal melanocytic proliferation, renal cancer metastasis, connective tissue neoplasm and salivary gland fistula. Both drugs share significant ADRs including palmar-plantar erythrodysesthesia syndrome, disease progression and hyperkeratosis."

Adverse events • Review • Gastrointestinal Stromal Tumor