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

PRAC adopted updates to the SmPC for avapritinib, adding drug–drug interaction data with CYP3A substrates from the phase 1 BLU-285-1107 study in unresectable or metastatic GIST and other solid tumors. Findings were supported by PBPK modelling to simulate effects at lower doses. (European Medicines Agency) - Pharmacovigilance Risk Assessment Committee (PRAC)-Draft agenda for the meeting on 1 - 4 Sep 2025: The Package Leaflet, RMP v5.0, and PI (aligned with QRD v10.4) were also updated. [AI-generated summary]

PRAC • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology

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

Long-term quality of life and safety in patients with indolent systemic mastocytosis treated with avapritinib in the PIONEER study (ADO 2025) - No abstract available

Clinical • HEOR • Oncology

Avapritinib and Bone Health in Indolent Systemic Mastocytosis: Learnings from the PIONEER Trial (ASBMR 2025) - P2 | No abstract available

Avapritinib Durably Improves Cutaneous Involvement of Indolent Systemic Mastocytosis in Patients Treated in the PIONEER Study (EADV 2025) - No abstract available

Clinical • Dermatology

Mast Cell Leukemia: Comprehensive Review of Literature With Current Insights and Updates on Management. (PubMed, J Hematol) - "The two targeted therapies approved for MCL are midostaurin, a multikinase inhibitor, and avapritinib, a selective KIT D816V mutation-targeted tyrosine kinase inhibitor. In this article, we conducted a comprehensive yet simplified review of MCL, focusing primarily on its clinical manifestations and recent updates on management. We also identified the areas that require further research and emphasized the aggressive nature and poor prognosis associated with this disease."

Journal • Review • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Oncology • Transplantation

Assessment of the metabolic stability of avapritinib in human liver microsomes using a fast and green UPLC-MS/MS method: screening for structural alarms associated with metabolic lability and in silico toxicity. (PubMed, Anal Methods) - "APB and encorafenib (ECB as the internal standard) were separated using an isocratic mobile phase approach on an Agilent SB-C18 (reversed-phase) column. The metabolic stability characteristics including the intrinsic clearance and the in vitro half-life of APB were determined to be 22.11 mL min-1 kg-1 and 36.67 min, respectively. In silico analysis suggests that minor structural changes to the methyl pyrazole moiety in drug design may improve the metabolic stability and safety relative to APB."

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

Avapritinib improves symptoms and quality of life in indolent systemic mastocytosis: 6-month real-world outcomes from the AVATAR study (EADV 2025) - No abstract available

Clinical • HEOR • Real-world • Real-world evidence • Cardiovascular • Dermatology • Dermatopathology • Immunology • Urticaria

Avapritinib Durably Improves Cutaneous Involvement of Indolent Systemic Mastocytosis in Patients Treated in the PIONEER Study (EADV 2025) - No abstract available

Clinical

A Rare Case of Acute Aleukemic Mast Cell Leukemia With Osteoblastic Lesions in the Appendicular Skeleton (SOHO 2025) - "We described here a very rare case of aleukemic MCL with diffuse osteoblastic metastatic bone lesions involving axial and appendicular skeleton. With this case, we would like to report that MCL is a malignancy that can present with both osteolytic and osteoblastic bone lesions and stress the importance of bone biopsy in suspected cases of MCL. The mainstay of management of MCL includes targeted chemotherapies, midostaurin or avapritinib, and supportive measures."

Clinical • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Oncology • ANPEP • CD33 • CD4 • KIT

Favorable Benefit-Risk Profile of Avapritinib in Indolent Systemic Mastocytosis Is Maintained After 3 Years of Therapy: Longer-Term Analysis of the PIONEER Study (SOHO 2025) - P2 | "Longer follow-up of patients with ISM in the PIONEER trial, including some on avapritinib for up to 5 years, demonstrates that prolonged avapritinib therapy continues to be effective and generally well tolerated. These data support a favorable benefit-risk profile of avapritinib as a chronic treatment for adult patients with ISM."

Oncology

More Than Just a Gut Feeling: Unmasking Systemic Mastocytosis Behind Chronic GI Symptoms (ACG 2025) - "These findings fulfilled both the major and minor diagnostic criteria for systemic mastocytosis, specifically the indolent variant.After trials with multiple medications, the patient's symptoms have been controlled with fexofenadine, montelukast, and famotidine. Other medications included Cromolyn, which was discontinued due to poor adherence, and a trial drug, Avapritinib, which was stopped due to lower extremity edema and weight gain. This case illustrates the diagnostic and therapeutic challenges of GI involvement in systemic mastocytosis...A low-histamine diet, escalated antihistamine therapy, and consideration of advanced therapies may also provide symptomatic relief and improve quality of life.Figure: Esophagogastroduodenoscopy (EGD) revealed diffuse moderate inflammation in the second portion of the duodenum, charactherized by mucosal congestion, erythema, and nodularity. Figure: Colonoscopy revealed diffuse moderate inflammation in the proximal transverse..."

Barrett Esophagus • Cardiovascular • Celiac Disease • Dermatology • Gastroenterology • Gastroesophageal Reflux Disease • Gastrointestinal Disorder • Hypertension • Immunology • Inflammation • Osteoporosis • Rare Diseases • Rheumatology • KIT

Innovative Therapeutic Approaches in Systemic Mastocytosis: an Updated Review. (PubMed, Maedica (Bucur)) - "The approval of tyrosine kinase inhibitors (TKIs), particularly midostaurin and avapritinib, has provided new therapeutic options for patients with advanced SM, demonstrating significant improvements in overall survival (OS) and symptom control. The present review provides an updated overview of the evolving therapeutic landscape of SM, emphasizing recent clinical trial data, novel targeted therapies and emerging treatment paradigms. We discuss the implications of this progress on patient outcomes and future directions for personalized medicine in SM."

Journal • Transplantation

Successful venom immunotherapy with avapritinib in a patient with systemic mastocytosis. (PubMed, Ann Allergy Asthma Immunol) - No abstract available

Journal

The evaluation, management, and future of indolent systemic mastocytosis. (PubMed, Ann Hematol) - "Furthermore, management strategies start with symptomatic support and can include targeted KIT inhibition, such as avapritinib, for patients with refractory disease...While many patients have stable disease, a subset may experience persistent morbidity or disease progression. Future directions include improving early recognition, validating biomarkers for monitoring and therapeutic response, and evaluating investigational therapies aimed at modifying disease course."

Journal • Review • Hematological Disorders • Hematological Malignancies • Oncology

Tyrosine Kinase Inhibitors for the Treatment of Mast Cell Diseases: Review and Update. (PubMed, J Investig Allergol Clin Immunol) - "TKIs represent a major advance in the management of MCDs, with more patients being able to benefit from a treatment that addresses pathophysiology. We review the main TKIs currently available for SM, their indications, and their safety and effectiveness."

Journal • Review • Bone Marrow Transplantation • Transplantation • KIT

Avapritinib versus midostaurin or cladribine in advanced systemic mastocytosis: A retrospective real-world external control study. (PubMed, Leuk Res) - P1, P2 | "Results were similar in treatment-naïve (1 L) and previously treated (2 L+) patients; there was improved OS in 1 L avapritinib vs. 1 L midostaurin patients (HR: 0.14 [0.05, 0.42]; p < 0.001) and in 2 L+ avapritinib vs. 2 L+ cladribine patients (0.34 [0.16, 0.71]; p = 0.004). Together, we show that avapritinib treatment resulted in significantly improved OS, longer DOT, and greater reduction in serum tryptase levels compared to midostaurin or cladribine in real-world clinical practice."

Journal • Real-world evidence • Retrospective data

Press Release: Sanofi completes acquisition of Blueprint Medicines (Sanofi Press Release) - "Sanofi today announces the completion of its acquisition of Blueprint Medicines Corporation (Blueprint), adding to its portfolio a commercialized medicine, a promising pipeline, and the expertise of a company specializing in systemic mastocytosis (SM), a rare immunological disease, and other KIT-driven diseases....The acquisition includes a rare immunology disease medicine, Ayvakit/Ayvakyt (avapritinib), approved in the US and EU....The acquisition also includes elenestinib, a next-generation medicine for SM that is a potent and highly selective KIT D816V inhibitor with limited central nervous system penetration....Sanofi also acquired BLU-808, an investigational oral, highly potent and selective wild-type KIT inhibitor."

M&A • Aggressive Systemic Mastocytosis • Immunology

Avapritinib for systemic mastocytosis with an associated myelodysplastic/myeloproliferative neoplasm: a case report and literature review (PubMed, Zhonghua Xue Ye Xue Za Zhi) - "Although avapritinib, a novel targeted therapy, has significantly improved outcomes for SM, the efficacy of treatment for the associated hematologic neoplasm in patients with SM-AHN may be the primary determinant of long-term overall survival and progression-free survival. This report includes a review of relevant literature to provide insights into the clinical diagnosis and management of this rare entity."

Journal • Review • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology

Integrating a Rare Disease into Practice: Development of a Toolkit for Systemic Mastocytosis. (PubMed, J Adv Pract Oncol) - "The emergence of targeted therapies, such as avapritinib for both advanced and indolent SM, has further highlighted the need for AP education on novel disease mechanisms and treatment strategies. This project demonstrates a replicable model for developing educational and clinical resources to support APs in managing rare diseases and improving patient-centered care."

Journal • Hematological Disorders • Oncology • Rare Diseases

Management of indolent mastocytosis and mast cell activation syndrome: A clinical yardstick. (PubMed, Ann Allergy Asthma Immunol) - "Unfortunately, there is some lack of guidance on how best to utilize these therapies. This yardstick aims to provide the clinician with a review of available therapies to treat mast cell activation syndrome and indolent systemic mastocytosis and an evidence-based expert opinion approach regarding how best to utilize these therapies."

Journal

Avapritinib monotherapy induces rapid and deep remission of heavily treated, KIT D816H-mutated t(8;21) acute myeloid leukemia, a case report and literature review. (PubMed, Ann Hematol) - "Acute myeloid leukemia (AML) with t(8;21) is a subset of core binding factor AML and is considered to be favorable risk disease in patients receiving intensive cytarabine based chemotherapy. We present a case of a patient with extensively treated KIT D816H-mutated t(8;21) AML who experienced relapse after an allogeneic hematopoietic stem cell transplant and achieved a deep remission rapidly with avapritinib monotherapy. This case highlights the potential role of avapritinib as a targeted therapy for relapsed t(8;21) AML with KIT mutations, warranting further clinical investigation."

Journal • Monotherapy • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation

Absolute Configuration and Chiroptical Properties of Flexible Drug Avapritinib. (PubMed, Pharmaceuticals (Basel)) - "Biological evaluation revealed (S)-(-)-avapritinib exhibited superior c-KIT D816V inhibitory activity compared to its (R)-(+)-counterpart, a finding corroborated by molecular docking studies elucidating their differential target interactions. This study advances avapritinib stereochemical understanding and establishes a definitive protocol for its absolute configuration assignment, serving as a paradigm for flexible chiral drug characterization."

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

A New Treatment of Newly Diagnosed KIT Mutation CBF-Acute Myeloid Leukemia (clinicaltrials.gov) - P1/2 | N=78 | Recruiting | Sponsor: The First Affiliated Hospital of Soochow University

New P1/2 trial • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology