Ayvakit (avapritinib) / CStone Pharma, Sanofi - LARVOL DELTA

Anaphylaxis events in the PIONEER study of avapritinib in indolent systemic mastocytosis. (PubMed, World Allergy Organ J) - P2 | "During the randomized, placebo-controlled treatment period, 4/141 (2.8%) avapritinib-treated patients and 3/71 (4.2%) placebo-treated patients experienced anaphylaxis. Larger studies with longer-term follow-up are required to further confirm the effects of avapritinib on anaphylaxis in patients with SM."

Journal

Efficacy and safety of avapritinib in advanced systemic mastocytosis: 4-year follow-up of the PATHFINDER study. (PubMed, Blood Adv) - P2 | "Eleven (10%) patients experienced TEAEs leading to death, of which 1 was deemed related to avapritinib by the principal investigator. With 4-year follow-up, avapritinib-treated patients with AdvSM experienced deep and durable responses and a favorable benefit-risk profile."

Journal • Hematological Disorders • Hematological Malignancies • Oncology • Thrombocytopenia • KIT

Efficacy of Avapritinib on Cutaneous Manifestations in Systemic Mastocytosis: A Systematic Review and Meta-analysis (AAD 2026) - "In conclusion, avapritinib demonstrated consistent efficacy with improvement in skin manifestations across both ISM and AdvSM."

Retrospective data • Review • Hematological Malignancies • TNFRSF8

Avapritinib Achieves Durable Improvement in Skin Findings With a Well-Tolerated Safety Profile in Patients With Indolent Systemic Mastocytosis (ISM): Long-term Analyses From the PIONEER Study (AAD 2026) - P2 | "Avapritinib elicited long-term disease modification seen as durable improvements in ISM-related skin lesions (area and color) and symptoms. Avapritinib was well tolerated long term."

Clinical • Pruritus • KIT

Using in vitro models to predict imatinib responses in PDGFRA-mutant gastrointestinal stromal tumor (AACR 2026) - "Avapritinib (AVA), a type I TKI, was developed and is FDA-approved for all PDGFRA exon 18 mutant GIST but is costly and has severe cognitive side effects in some patients. Lastly, we determined that our results are concordant with first-line IM response data, as patients with predicted IM-sensitive mutations experienced a longer median progression-free survival than those with predicted or known IM-resistant mutations (30 vs 4 months, p <0.0001). Our work highlights an approach to optimize clinical guidelines for the TKI treatment for PDGFRA-mutant GIST based on specific patient mutations."

Preclinical • Stroma • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Solid Tumor • KIT • PDGFRA

BRUGADA PATTERN UNMASKED BY TYROSINE KINASE INHIBITOR THERAPY IN A PATIENT WITH A JPH2 MUTATION (ACC 2026) - "Decision-Making: The patient had failed two prior TKIs - imatinib for a treatment-limiting skin rash, and nilotinib for refractory pain, leaving limited oncologic options. FDA review indicates that avapritinib can inhibit cardiac sodium-channel activity (reported IC₅₀ ≈ 0.3 µM), providing a biologically plausible mechanism by which the drug, particularly when combined with high-grade fever, could transiently reduce INa and unmask a Type I Brugada EKG pattern. In our patient the Brugada pattern normalized with defervescence and brief interruption of avapritinib, and continuous monitoring revealed no ventricular arrhythmias. This case highlights TKI-related sodium-channel effect warranting vigilance."

Clinical • Cardiovascular • Genetic Disorders • Sarcoma • Solid Tumor

Development of an Optimized superRCA KIT D816V Test for Mast Cell–Driven Diseases (USCAP 2026) - P1/2, P2 | "Clinical validity of the optimized superRCA assay was assessed in PB from healthy donors and patients with ISM previously tested for KIT D816V by ddPCR in PIONEER (NCT03731260; limit of detection [LOD]: 0.022%) and HARBOR (NCT04773782; LOD: 0.03%) studies of avapritinib and elenestinib. The optimized superRCA assay improved KIT D816V detection, with ≥30-fold higher sensitivity than ddPCR without loss of specificity, expanding the diagnostic toolkit for clonal mast cell disease, including ISM."

Tumor mutational burden • TMB

Severe cognitive effects of avapritinib: Towards a mechanistic understanding (Sarcoma-RC 2026) - "Legal entity responsible for the study Neeltje Steeghs. Funding Has not received any funding."

CNS Disorders • Sarcoma • Vascular Neurology • PDGFRA • PDGFRB

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

Mice Expressing KITD814V In The Mast Cell Lineage Show a Systemic Mastocytosis Phenotype with Skin Lesions That Can Be Reversed By Treatment With Specific Tyrosine Kinase Inhibitors (AAAAI 2026) - "Moreover, avapritinib-treated mice showed no scratching bouts, indicating resolution of chronic itch. Conclusions Mctp5-Cre KITD814V mice present an indolent systemic mastocytosis phenotype, which is corrected by treatment with the tyrosine kinase inhibitor avapritinib, suggesting its relevance as a preclinical model."

Preclinical • CCL2 • IL16 • IL6 • TNFA

Initiation of Treatment with FDA-Approved Avapritinib in a Cohort of Patients with Indolent Systemic Mastocytosis: Practical Experience and One Year Follow-up (AAAAI 2026) - "Conclusions Avapritinib was well tolerated and led to significant reductions in symptoms and mast cell burden in patients with ISM. These findings support its use as a first-line therapy in KIT D816V-positive ISM with high mast cell burden and mediator-driven symptoms."

Clinical

Real-World Experience of Patients with Indolent Systemic Mastocytosis Treated with Avapritinib in a Community Oncology Setting (AAAAI 2026) - "At end of follow-up (median 14.2 months) 15/18 patients remained on therapy. Conclusions Avapritinib was well-tolerated and led to rapid symptom improvement in patients with ISM in community practice, supporting its real-world clinical utility."

Clinical • Real-world • Real-world evidence

Long-Term Bone Health Outcomes in Patients Treated with Avapritinib for Indolent Systemic Mastocytosis: Findings from the PIONEER study (AAAAI 2026) - P2 | "Mean (SD) percent increase in lumbar spine BMD were: Year 1, 1.66% (5.57%), n=59; Year 3, 4.05% (5.78%), n=26. Conclusions Long-term avapritinib was associated with improvements in lumbar spine BMD and PINP, supporting further research with disease-modifying therapy on bone health in ISM."

Clinical • HEOR • Musculoskeletal Diseases • Orthopedics • Osteoporosis • TRAP

Ultra-Sensitive SuperRCA Assay Enhances the Ability to Detect KIT D816V Mutations in Peripheral Blood With a Sensitivity Comparable to That of Bone Marrow Testing (AAAAI 2026) - P1/2, P2 | "We compared KIT D816V detection with each method and baseline characteristics for ddPCR detectable (ddPCR+) versus ddPCR undetectable (ddPCR–)/superRCA detectable (superRCA+) patients from PIONEER (NCT03731260) and HARBOR (NCT04773782) studies of KIT inhibitors avapritinib (approved for ISM) and investigational elenestinib. Baseline median serum tryptase and BM mast cells were significantly higher in ddPCR+ versus ddPCR–/superRCA+ patients (P<0.0001). Conclusions The superRCA assay increased PB KIT D816V detection comparable with local BM testing, highlighting the potential for ultra-sensitive testing to improve ISM diagnosis, especially with low baseline serum tryptase."

Tumor mutational burden • TMB

A Systematic Literature Review of Avapritinib Outcomes in Patients with Indolent Systemic Mastocytosis (AAAAI 2026) - P2 | "These findings are supported by results from the real-world study. Conclusions This SLR provides the most current and comprehensive compilation of outcomes data for patients with ISM treated with avapritinib which can inform evidence-based clinical decision-making for this population."

Clinical • Review

Avapritinib Durably Improves Gastrointestinal Symptoms of Indolent Systemic Mastocytosis: Long-Term Outcomes From the PIONEER Study (AAAAI 2026) - P2 | "Cromolyn sodium and antihistamine use was also reduced. These clinically meaningful findings, and consistently well-tolerated safety profile, support long-term avapritinib use for ISM-related symptom reduction."

KIT

PIONEER: Long-Term Data Reinforce AYVAKIT as Durable Standard of Care in ISM (PRNewswire) - "In patients with frequent episodes of diarrhea at baseline and at least four years of AYVAKIT (n=44), the median reduction in diarrhea frequency was 65.6 percent. In the overall clinical study population, individual GI symptoms meaningfully improved, allowing for decreased use of cromolyn sodium and other supportive care medicines. Patients had increased bone mineral density – a clinical measure of disease-modifying effects – in the lumbar spine, left total hip and left femoral neck after three years of AYVAKIT. In PIONEER, the change in bone mineral density was assessed in patients who received dual-energy X-ray absorptiometry (DXA) scans (n=79)."

P2 data • Hematological Malignancies

Avapritinib continues to demonstrate durable symptom control with a well-tolerated safety profile: Long-term outcomes from PIONEER (AAAAI 2026) - P2 | "Conclusions At ∼3.5 years, avapritinib continues to demonstrate durable, clinically meaningful improvements in symptoms and QoL with a well-tolerated safety profile at 25 mg and 50 mg QD. Avapritinib shows a favorable benefit-risk profile for chronic use in adult patients with ISM."

Clinical

Real-World Evidence Further Validates Clinical Benefit of AYVAKIT in ISM (PRNewswire) - "A retrospective review of electronic medical records was conducted at ONCare Alliance, a network of community oncology practices, to assess the impact of AYVAKIT in the real-world setting. Median follow-up was 14.2 months. In AYVAKIT-treated patients (N=18), the median time to symptom improvement was rapid (36.5 days). Benefits were frequently reported across a range of symptoms, including GI, skin, abdominal pain and headache symptoms. Among patients who initiated the 25 mg daily dose of AYVAKIT (n=16), 87.5 percent have remained on therapy, reflecting a well-tolerated safety profile."

Real-world evidence • Hematological Malignancies

Lack of Disease Control and Substantial Burden in Patients with ISM (PRNewswire) - "In collaboration with APSHO and TMS, a survey was developed to identify factors affecting perceptions of disease control in patients with ISM (N=53). Three-quarters of patients (75 percent; n=40) reported that their disease was not optimally controlled. Patients reported severe symptoms regardless of their perceived disease control, underscoring the significant burden across the spectrum of ISM."

Clinical data • Hematological Malignancies

AVAPRITINIB DURABLY IMPROVES GASTROINTESTINAL SYMPTOMS OF INDOLENT SYSTEMIC MASTOCYTOSIS: LONG-TERM OUTCOMES FROM THE PIONEER STUDY (DDW 2026) - No abstract available

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

Cytoreduction is a Valid Option for Treatment and Prevention of Anaphylaxis in Systemic Mastocytosis: Case Report and Literature Review. (PubMed, Clin Rev Allergy Immunol) - No abstract available

Journal • Review

Metadynamics reveals luteolin-mediated conformational stabilization against avapritinib-resistant PDGFRα D842V/G680R GIST. (PubMed, Sci Rep) - No abstract available

Journal • Oncology • PDGFRA

Avapritinib improves cutaneous involvement in patients with indolent systemic mastocytosis: Results from the randomized, phase 2, interventional PIONEER study. (PubMed, J Am Acad Dermatol) - P2 | "Avapritinib treatment improved dermatologic symptoms, decreased skin lesion size, normalized skin lesion color, and reduced skin mast cell burden in patients with ISM."

Journal • P2 data • Rare Diseases