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

The Evolving Role of Second- and Third-Generation Tyrosine Kinase Inhibitors in Gastrointestinal Malignancies: Advances in Targeted Therapy with Sunitinib, Regorafenib, and Avapritinib. (PubMed, J Clin Med) - "While imatinib revolutionized first-line therapy, resistance and specific mutation profiles necessitate subsequent generations of tyrosine kinase inhibitors (TKIs). Second- and third-generation TKIs have transformed the management of advanced GIST, extending survival and offering mutation-specific precision therapy. Ongoing research into resistance mechanisms, combination strategies, and novel inhibitors promises further optimization of patient-centered care."

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

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

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

Press release: 2025: strong sales and EPS growth. Continued profitable growth expected in 2026 (The Manila Times) - "Pharma launches increased sales by 49.4%, reaching €1.1 billion, primarily driven by Ayvakit and ALTUVIIIO"

Commercial • Aggressive Systemic Mastocytosis • Hemophilia A

Circulating tumor DNA (ctDNA) analyses of the phase III VOYAGER trial: KIT mutational landscape and outcomes in patients with advanced gastrointestinal stromal tumor (GIST). (ASCO 2022) - P3 | "Background: The genotype of primary mutations predicts imatinib response in untreated metastatic GIST...Regorafenib showed similar activity regardless of KIT mutational status and the location of KIT mutation... Hybrid capture-based plasma sequencing detects ctDNA in the majority of patients with advanced TKI-resistant GIST, including heterogeneity of KIT mutations. This study is the first to show that ctDNA sequencing correlates with outcomes in pretreated GIST. Identification of ABP (exon13/14) KIT mutations negatively correlates with avapritinib activity."

Circulating tumor DNA • Clinical • P3 data • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • KIT • PDGFRA

Journal Club: Mastocytosis: across the spectrum: pathobiology, clinical evaluation, and evolving therapies. (PubMed, Eur J Dermatol) - "Midostaurin and avapritinib have reshaped the treatment of AdvSM, while next-generation tyrosine-kinase inhibitors (TKIs) are in clinical trials. Multidisciplinary care is critical, and knowledge gaps remain in paediatric risk stratification, optimal sequencing of therapies, and disease progression assessment. This review highlights recent advances and future priorities for personalized, evidence-based care."

Journal • Review • Pediatrics • Rare Diseases

Ayvakit (mastocytosis) sales were €168 million. (GlobeNewswire) - "Sales were split between the US (€148 million) and Europe (€20 million) with continued growth in the number of patients treated. Sales growth was partly offset by shipping patterns in the US, and an element of price adjustment. In the full year, pro-forma sales reached $725 million, slightly ahead of Blueprint expectations from earlier in the year ($700-720 million). Sanofi does not hold marketing rights in China but receives royalty on sales by CStone Pharmaceuticals."

Sales • Aggressive Systemic Mastocytosis

Circulating tumor DNA analysis of the phase III VOYAGER trial: KIT mutational landscape and outcomes in patients with advanced gastrointestinal stromal tumor treated with avapritinib or regorafenib. (PubMed, Ann Oncol) - P3 | "CtDNA sequencing efficiently detects KIT/PDGFRA mutations and prognosticates outcomes in patients with TKI-resistant GIST treated with avapritinib. ctDNA analysis can be used to monitor disease progression and provide more personalized treatment."

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

Case Report: A rare case of synchronous ovarian mixed germ cell tumor and mast cell leukemia in a pediatric patient. (PubMed, Front Oncol) - "Targeted therapy with avapritinib and ruxolitinib was initiated but yielded limited response. Given the consistent co-occurrence of KIT mutations in previously reported similar cases, we propose the recognition of a distinct disease entity: ovarian germ cell tumor/mastocytosis with KIT mutations. This report emphasizes the importance of early genetic profiling and multidisciplinary collaboration in diagnosing and managing rare, genetically unified malignancies in pediatric oncology."

Journal • Cognitive Disorders • Germ Cell Tumors • Hematological Disorders • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Oncology • Ovarian Cancer • Pediatrics • Solid Tumor • Thrombocytopenia • AFP • KIT • NRAS • TP53

Prospective Study of Avapritinib in Patients with Relapsed/Refractory or MRD-Positive Core-Binding Factor Acute Myeloid Leukemia with KIT Mutations (ASH 2024) - "In general, the study results suggest that avapritinib demonstrated good efficacy and safety in patients with CBF-AML harboring KIT gene mutations. These findings may support expanding the indications for this therapy in the treatment of AML."

Clinical • Minimal residual disease • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • Respiratory Diseases • Sarcoma • CBFB • KIT • PDGFRA • RUNX1 • RUNX1T1

THE REVISED MUTATION-ADJUSTED RISK SCORE (MARS-R) FOR PREDICTING OVERALL SURVIVAL IN PATIENTS WITH ADVANCED SYSTEMIC MASTOCYTOSIS TREATED WITH MIDOSTAURIN OR AVAPRITINIB (EHA 2025) - P1, P2 | "The MARS-R captures the continuum of OS risk observed among AdvSM pts, stratifying them into 3 distinct risk categories for treatment with midostaurin or avapritinib. It serves as an important new tool for clinical management of AdvSM patients, particularly regarding treatment maintenance or intensification, such as with allogeneic hematopoietic cell transplantation."

Clinical • Metastases • Aggressive Systemic Mastocytosis • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Oncology • ASXL1 • RUNX1 • SETBP1

Avapritinib As First-Line Therapy in Patients with Advanced Systemic Mastocytosis: Efficacy and Safety from the Pathfinder Clinical Study (ASH 2022) - P1, P2 | "Avapritinib demonstrated a high level of efficacy as the first-line therapy for patients with AdvSM across all disease subtypes with an ORR of 84% and an OS rate of 88% at 2 years. Avapritinib treatment with a 200 mg once-daily starting dose was generally well-tolerated."

Clinical • Anemia • Hematological Disorders • Hematological Malignancies • Immunology • Myeloproliferative Neoplasm • Neutropenia • Oncology • Thrombocytopenia

Safety and efficacy of avapritinib in advanced systemic mastocytosis: the phase 1 EXPLORER trial. (PubMed, Nat Med) - P1 | "Avapritinib elicited ≥50% reductions in marrow mast cells and serum tryptase in 92% and 99% of patients, respectively. Avapritinib induced deep and durable responses, including molecular remission of KIT D816V in patients with AdvSM, and was well tolerated at the recommended phase 2 dose of 200 mg daily."

Clinical • Journal • P1 data • Hematological Disorders • Hematological Malignancies • Immunology • Oncology • Thrombocytopenia

AVAPRITINIB IN PATIENTS WITH ADVANCED SYSTEMIC MASTOCYTOSIS (ADVSM): EFFICACY AND SAFETY ANALYSIS FROM THE PHASE 2 PATHFINDER STUDY WITH 3-YEAR FOLLOW-UP (EHA 2024) - P1, P2 | "With >3 years of follow-up, patients with AdvSM treated with avapritinib showed continued deep and durableresponses with a favorable benefit-risk profile regardless of AdvSM subtype or prior therapy."

Clinical • Metastases • P2 data • Aggressive Systemic Mastocytosis • Anemia • Eosinophilia • Hematological Disorders • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia

Comparative Safety of Avapritinib, Midostaurin, and Cladribine in Systemic Mastocytosis: A Meta-Analysis (ACMG 2026) - "Grade ≥3 adverse events were prioritized because they reflect severe toxicities that directly impact treatment decisions, often requiring dose modification or discontinuation. This focus provides a clearer view of real-world tolerability among avapritinib, midostaurin, and cladribine. Avapritinib demonstrated a higher incidence of grade ≥ 3 hematologic adverse events but lower discontinuation rates, suggesting manageable toxicity with appropriate monitoring and dose adjustment."

Retrospective data • Hematological Disorders

Refractory cutaneous symptoms in systemic mastocytosis. (PubMed, JAAD Case Rep) - No abstract available

Journal

BLU-285-3101: A Study of Avapritinib in Pediatric Patients With Solid Tumors Dependent on KIT or PDGFRA Signaling (clinicaltrials.gov) - P1/2 | N=29 | Completed | Sponsor: Blueprint Medicines Corporation | Active, not recruiting ➔ Completed

Trial completion • Brain Cancer • CNS Tumor • Oncology • Pediatrics • Solid Tumor • KIT • PDGFRA

BLU-285-2407: A Non-Interventional Study in Participants With Indolent Systemic Mastocytosis (ISM) in Germany (clinicaltrials.gov) - P=N/A | N=80 | Recruiting | Sponsor: Blueprint Medicines Corporation | Not yet recruiting ➔ Recruiting

Enrollment open • Real-world evidence

The efficacy of avapritinib for unresectable or metastatic gastrointestinal stromal tumors with and without PDGFRA D842V mutations: A meta-analysis. (ASCO-GI 2026) - "Although avapritinib is approved for first-line treatment for GIST with PDGFRA exon 18 mutations, few PDGFRA D842V patients achieved a CR. Future studies should compare the efficacy of avapritinib to novel therapies in PDGFRA D842V patients to identify optimal treatments. This analysis found avapritinib has low efficacy in all UM GIST and those without the PDGFRA D842 mutation."

Metastases • Retrospective data • Stroma • Gastrointestinal Cancer • Oncology • PDGFRA

Avapritinib in the treatment of systemic mastocytosis with associated acute myeloid leukemia after poor graft function following allogeneic hematopoietic stem cell transplantation: a case study and review of the literature. (PubMed, Front Oncol) - "It suggests that avapritinib may bridge therapeutic gaps for atypical KIT-mutant systemic mastocytosis with associated hematologic neoplasm (SM-AHN) that is ineligible for Allo-HSCT or relapsed. Prospective trials are warranted to validate its efficacy, optimize dosing, and explore synergies with Allo-HSCT, offering new strategies for these high-risk patients."

Journal • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Transplantation • RUNX1 • RUNX1T1

Avapritinib and corticosteroids in advanced systemic mastocytosis with tumoral CMML and associated thrombocytopenia. (PubMed, Oxf Med Case Reports) - "Initial treatment with midostaurin and azacitidine was discontinued due to hematological toxicity. Clinical improvement was observed within two weeks, with lymphadenopathy resolution, spleen and liver size reduction, platelet count normalization, and serum tryptase decrease. Avapritinib combined with dexamethasone offers a promising therapeutic strategy for SM-AHN, particularly in thrombocytopenic cases."

Journal • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Thrombocytopenia

Correlates of organ damage in patients with advanced systemic mastocytosis enrolled in clinical trials of avapritinib. (PubMed, Blood Neoplasia) - "Notably, 47% of patients received previous midostaurin. AdvSM subtype, the presence and number of additional comutated genes beyond KIT D816V, BM mast cell burden, and KIT D816V variant allele fraction were associated with the presence and/or number of WHO/mIWG organ damage findings. Our study provides a snapshot of the correlates of organ damage in patients enrolled in clinical trials of avapritinib and identifies a key association between molecular profile and burden of organ damage."

Journal • Aggressive Systemic Mastocytosis • Hematological Disorders • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Oncology • ASXL1 • RUNX1 • SRSF2

Consideration of Off-Label Therapies as Appropriate Comparator Therapy in Early Benefit Assessments in Germany Under the ALBVVG Legislation (ISPOR-EU 2025) - "The G-BA decisions regarding the choice of ACT were analyzed with a focus on the reasoning provided in the supporting documents. The selected EBA procedures showed varying outcomes: For dupilumab (eosinophilic esophagitis), an established off-label therapy was considered appropriate based on evidence-based guidelines and extensive clinical experience. For midostaurin (systemic mastocytosis), avapritinib, cladribine, and imatinib were recognized as ACT despite not all being approved for the corresponding indication, acknowledging their established role in treatment algorithms. For lisocabtagene maraleucel (various B-cell lymphomas after prior therapy), off-label use was deemed appropriate, particularly considering the disease severity and limited therapeutic alternatives for these vulnerable patients. Conversely, for talazoparib (metastatic castration-resistant prostate carcinoma), the off-label use of abiraterone acetate with prednisone/prednisolone and enzalutamide was..."

B Cell Lymphoma • Castration-Resistant Prostate Cancer • Eosinophilic Esophagitis • Gastrointestinal Disorder • Genito-urinary Cancer • Hematological Malignancies • Immunology • Lymphoma • Non-Hodgkin’s Lymphoma • Prostate Cancer • Solid Tumor

Systemic mastocytosis with associated lymphoid neoplasms (SM-ALN): A distinct subset with indolent clinical course and favorable outcomes (ASH 2025) - "SM management was divided into two categories: (1) Conservative approach, including observation alone in 4 patients (22%) and symptomatic therapies such as antihistamines or leukotriene inhibitors in 7 (39%); and (2) Cytoreductive treatments, comprising avapritinib in 5 patients (28%), cladribine in 1 (6%), and imatinib in 1 (6%). Management of lymphoid neoplasms included intensive regimens such as R-CHOP and hyper-CVAD for high-grade subtypes (e.g., DLBCL and T-ALL), while indolent forms (e.g., CLL and follicular lymphoma) were treated with bendamustine-rituximab or observation depending on disease burden... SM-ALN is a rare but distinct SM subtype characterized by indolent behavior, favorable treatment responses, and prolonged survival. Recognition of this subset is critical to avoid over-treatment and to guide risk-adapted management strategies."

Clinical • Acute Lymphocytic Leukemia • Aggressive Systemic Mastocytosis • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Dermatology • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Indolent Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Pruritus • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • ASXL1 • CCND3 • CXCR4 • DNMT3A • IDH1 • JAK2 • KIT • MYD88 • NOTCH2 • RUNX1 • SF3B1 • SRSF2 • TET2 • TP53

Combinatorial targeting of avapritinib-driven MAPK activation in pediatric high-grade glioma (SNO 2025) - "Combinatorial treatment of pHGG models with MEK (selumetinib, trametinib), ERK (ulixertinib) and integrated stress/ERK inhibitors (ONC201, ONC206) in vitro eradicated pERK activity. A patient with an un-resected PDGFRα-mutant pHGG treated with avapritinib and selumetinib prior to progression demonstrated complete and ongoing tumor regression (12 months+). Considering sustained MAPK activation identified in our study, dual avapritinib-MAPK targeted treatment may be an effective approach for PDGFRΑ-driven pHGG."

Clinical • Brain Cancer • CNS Tumor • Glioma • High Grade Glioma • Pediatrics • Solid Tumor • MCL1 • PDGFRA