Ayvakit (avapritinib) / Blueprint Medicines, CStone Pharma - LARVOL DELTA

Evaluation of the effectiveness and safety of avapritinib in real-world Spanish cases with gastrointestinal stromal tumor and D842V-PDGFRA mutation. (PubMed, Oncologist) - "Avapritinib extends PFS and OS among patients with PDGFRA D842V-mutant GIST in real-world practice, mirroring pivotal trial outcomes. Its substantial activity supports its use as a first-line therapy for this subgroup. The manageable safety profile reinforces avapritinib viability for routine use. Given the rarity of these cases, it is advised to consult sarcoma-expert units."

Journal • Observational data • Real-world evidence • Retrospective data • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Solid Tumor • PDGFRA

Targeted inhibition of PDGFRA with avapritinib, markedly enhances lenvatinib efficacy in hepatocellular carcinoma in vitro and in vivo: clinical implications. (PubMed, J Exp Clin Cancer Res) - "Our findings demonstrate that PDGFRA overexpression mediates lenvatinib resistance in HCC and that targeting PDGFRA with avapritinib, surmounts this resistance. Furthermore, the PTEN/AKT/GSK-3β/β-catenin pathway was implicated in lenvatinib resistance, providing a potential therapeutic strategy for HCC patients displaying lenvatinib resistance. Further clinical studies are warranted to validate these findings and to explore the clinical application of PDGFRA-targeted therapies in HCC treatment."

Journal • Preclinical • Hepatocellular Cancer • Oncology • Solid Tumor • PDGFRA • PTEN

Selecting optimal therapy in systemic mastocytosis: current state and future directions. (PubMed, Expert Opin Pharmacother) - No abstract available

Journal

“A full HTA is recommended to assess the clinical effectiveness and cost effectiveness of avapritinib compared with the current standard of care.” [For indolent systemic mastocytosis] (National Centre for Pharmacoeconomics, Ireland)

HEOR • Hematological Malignancies • Oncology

Blueprint Medicines Reports First Quarter 2025 Results and Raises AYVAKIT/AYVAKYT (avapritinib) Full Year Revenue Guidance (PRNewswire) - "Achieved AYVAKIT net product revenues of $149.4 million for the first quarter of 2025, including $129.4 million in the US and $20 million ex-US, representing 61% percent growth year-over-year....Revenues: Revenues were $149.4 million for the first quarter of 2025, generated by net product sales of AYVAKIT/AYVAKYT. Revenues were $96.1 million in the first quarter of 2024, including $92.5 million of net product revenues from sales of AYVAKIT/AYVAKYT and $3.6 million in collaboration revenues."

Commercial • Sales • Aggressive Systemic Mastocytosis • Gastrointestinal Stromal Tumor • Soft Tissue Sarcoma

(PATHFINDER) Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, in Patients With Advanced Systemic Mastocytosis (clinicaltrials.gov) - P2 | N=107 | Completed | Sponsor: Blueprint Medicines Corporation | Active, not recruiting ➔ Completed | Trial completion date: Jan 2026 ➔ Dec 2024 | Trial primary completion date: Jan 2026 ➔ Dec 2024

Trial completion • Trial completion date • Trial primary completion date • Tumor mutational burden • Aggressive Systemic Mastocytosis • Hematological Disorders • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Oncology

Mastocytosis. (PubMed, Nat Rev Dis Primers) - "The preclinical and clinical development of KIT-D816V-targeting drugs, such as midostaurin or avapritinib, mark a milestone in improving management, the quality of life and survival in patients with SM. These agents induce major responses or even remission in people with advanced SM and lead to rapid improvement of mediator-related symptoms and quality of life in symptomatic patients."

Journal • Review • Hematological Malignancies • Oncology • Osteoporosis • Rare Diseases • Rheumatology • Sarcoma • Solid Tumor

TGRX-3544 is a highly potent and mutant-selective degrader of oncogenic KIT with oral activity (AACR 2025) - "The cellular activity of TGRX-3544 against the E11, E17 and E11/E17 mutants was superior to that of all the currently approved KIT inhibitors imatinib, sunitinib, regorafenib, avapritinib and ripretinib. In summary, we have developed a highly mutant-selective, event-driven, scaffold-eliminating KIT degrader with superior cellular potency and in vivo oral activity. The balanced preclinical profile of TGRX-3544 supports its further clinical investigation in KIT-driven malignancies such as GIST and SM."

Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • ABL1 • BCR • EGFR • FLT3 • PDGFRA • STAT5

In melanoma, disruption of the NF1/SPRED1 RAS inactivating complex cooperates with mutant KIT necessitating combined KIT and MEK inhibition to suppress tumor growth (AACR 2025) - "In patient-derived melanoma cell lines with KIT mutations and loss of NF1 or SPRED1, combination treatment with a KIT inhibitor (imatinib or avapritinib) and a MEK inhibitor (trametinib) acted synergistically. Combined KIT and MEK inhibition also reduced tumor growth and prolonged survival of mice xenografted with KIT-mutant melanoma cell lines. Our findings suggest that combination therapy with KIT and MEK inhibitors would be beneficial for melanoma patients with activating KIT mutations and concomitant loss of function NF1/SPRED1 mutations."

Melanoma • Mucosal Melanoma • Oncology • Solid Tumor • KIT • NF1

AVAPRITINIB POST-ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR ADVANCED SYSTEMIC MASTOCYTOSIS: A CASE SERIES (EBMT 2025) - "After induction treatment with cytarabine, cladribine, idarubicin, and venetoclax, partial remission (PR) was achieved pre-alloHSCT...A molecular relapse of AHN was treated with azacitidine, venetoclax, and donor lymphocyte infusions (DLI), restoring and maintaining MRDneg. Ava was continued at 100 mg daily due to grade 3 thrombocytopenia.Patient 3 progressed from indolent systemic mastocytosis (ISM) to smoldering systemic mastocytosis (SSM) and ultimately to MCL...Initial treatments, including midostaurin and cladribine, reduced mast cell infiltration pre-alloHSCT but failed to achieve remission... Ava in the post-transplant setting was highly effective in all patients, with durable responses, including converting persistent disease to CR or MRDneg. The safety profile was favorable, with only one grade 3 thrombocytopenia resolved by dose reduction. Compared to the literature, these outcomes suggest prolonged OS."

Clinical • Metastases • Aggressive Systemic Mastocytosis • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Mast Cell Leukemia • Myeloproliferative Neoplasm • Oncology • Thrombocytopenia • Transplantation

OVERALL SURVIVAL AND DURATION OF TREATMENT IN PATIENTS WITH ADVANCED SYSTEMIC MASTOCYTOSIS RECEIVING AVAPRITINIB VERSUS MIDOSTAURIN OR BEST AVAILABLE THERAPY IN A REAL-WORLD SETTING (EBMT 2025) - P=N/A, P2 | "In IPTW-weighted Cox analysis, DOT was significantly longer in avapritinib versus midostaurin patients (HR [95% CI]: 0.37 [0.19, 0.70]; p=0.002).2L+ analysis: The avapritinib cohort included 67 patients, and the BAT cohort included 73 patients, contributing data on 104 lines of therapy (LOTs). Agent-level information was available for 89 LOTs in the BAT cohort, and common 2L+ agents were midostaurin (46.1%), cladribine (32.6%), and hydroxyurea (7.9%)... This study supports the use of avapritinib as 1L treatment for AdvSM, demonstrating significant OS and DOT benefits compared with 1L midostaurin. These results affirm that AdvSM patients with prior treatment experienced significantly improved OS and DOT on avapritinib compared to patients treated with BAT in the real world. Clinical Trial Registry: N/A"

Clinical • Metastases • Real-world • Real-world evidence • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology

OVERALL SURVIVAL AND DURATION OF TREATMENT IN PATIENTS WITH ADVANCED SYSTEMIC MASTOCYTOSIS RECEIVING AVAPRITINIB VERSUS MIDOSTAURIN OR BEST AVAILABLE THERAPY IN A REAL-WORLD SETTING (EBMT 2025) - P=N/A, P2 | "In IPTW-weighted Cox analysis, DOT was significantly longer in avapritinib versus midostaurin patients (HR [95% CI]: 0.37 [0.19, 0.70]; p=0.002).2L+ analysis: The avapritinib cohort included 67 patients, and the BAT cohort included 73 patients, contributing data on 104 lines of therapy (LOTs). Agent-level information was available for 89 LOTs in the BAT cohort, and common 2L+ agents were midostaurin (46.1%), cladribine (32.6%), and hydroxyurea (7.9%)... This study supports the use of avapritinib as 1L treatment for AdvSM, demonstrating significant OS and DOT benefits compared with 1L midostaurin. These results affirm that AdvSM patients with prior treatment experienced significantly improved OS and DOT on avapritinib compared to patients treated with BAT in the real world. Clinical Trial Registry: N/A"

Clinical • Metastases • Real-world • Real-world evidence • Myelodysplastic Syndrome • Myeloproliferative Neoplasm • Oncology

Cognitive toxicity of avapritinib: A case series (Sarcoma-RC 2025) - "Legal entity responsible for the study Axel de Bernardi. Funding Has not received any funding."

Clinical • Alzheimer's Disease • Cerebral Hemorrhage • Cognitive Disorders • Oncology • PDGFRA • PDGFRB

CRE25-047: Avapritinib Induced Pseudoprogression in a Gastrointestinal Stromal Tumor With a PDGFRA Exam 18 842 Mutation. (PubMed, J Natl Compr Canc Netw) - No abstract available

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

Targeted inhibition of PDGFRA with avapritinib, markedly enhances lenvatinib efficacy in hepatocellular carcinoma in vitro and in vivo: Clinical implications (APASL 2025) - "Our findings demonstrate that PDGFRA overexpression is associated with lenvatinib resistance in HCC and that targeting PDGFRA with avapritinib can overcome this resistance. The PTEN/AKT/GSK-3β pathway is implicated in the resistance mechanism, providing a potential therapeutic strategy for HCC patients with lenvatinib resistance. Further clinical studies are warranted to validate these findings and to explore the clinical application of PDGFRA-targeted therapies in HCC treatment."

Preclinical • Hepatocellular Cancer • Oncology • Solid Tumor • PDGFRA

AVAPTININIB AS A BRIDGE-TO-TRANSPLANT IN A CASE OF MAST CELL LEUKEMIA (EBMT 2025) - "The findings met WHO and ICC criteria for MCL.Starting in February 2023, midostaurin led to symptoms resolution after 6 months, but only to a partial response on marrow and extranodal disease...Treatment was well tolerated, with grade 1 conjunctivitis as the main side effect.After 10 months she underwent alloHCT from 10/10 HLA-matched unrelated donor after conditioning with treosulfan and fludarabine in July 2024. Graft-versus-Host disease (GvHD) prophylaxis was performed with post-transplant Cyclophosphamide, Mycophenolate Mofetil and Tacrolimus... MCL is a rare and aggressive disease and diagnosis could be difficult if the disease is not suspected. AlloHCT is the only curative option for MCL. Avaprtinib proved to be an effective bridge-to-transplant in our patient, allowing to deepen the clinical response without significant toxicity."

Clinical • Anemia • Conjunctivitis • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Mast Cell Leukemia • Ocular Infections • Ocular Inflammation • Oncology • Ophthalmology • Respiratory Diseases • Transplantation • IL2RA • TET2

Effective targeting of PDGFRA-altered high-grade glioma with avapritinib. (PubMed, Cancer Cell) - "Our early data demonstrate that avapritinib is well tolerated and results in radiographic response in 3/7 cases, suggesting a potential role for avapritinib in the treatment of HGG with specific PDGFRA alterations. Overall, these translational results underscore the therapeutic potential of PDGFRA inhibition with avapritinib in HGG."

Journal • Brain Cancer • CNS Tumor • Diffuse Midline Glioma • Glioblastoma • Glioma • Malignant Glioma • Oncology • Pediatrics • Solid Tumor • PDGFRA

Interaction of Avapritinib with Congo Red in Pancreatic Cancer Cells: Molecular Modeling and Biophysical Studies. (PubMed, Int J Mol Sci) - "Both tested compounds also affected the phosphorylation of the selected signaling proteins. We conclude that the selected tyrosine kinase inhibitor (alone) and in its co-aggregate with Congo red exhibit anticancer activity and should be considered as a novel effective therapy against pancreatic cancer."

Journal • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor • KIT

Low Bone Density: Positive Clinical Impact of AYVAKIT and Real-World Prevalence in ISM (PRNewswire) - "In a single-site case series from the PIONEER trial, AYVAKIT showed clinically meaningful and durable improvements in bone density, including in the lumbar spine, femoral neck and total proximal femur. In real-world data generated from Mayo Clinic electronic health records, 67 percent of ISM patients had osteoporosis/osteopenia compared to 34 percent in a matched control cohort (p<0.0001)."

Real-world evidence • Aggressive Systemic Mastocytosis

AYVAKIT: PIONEER Three-Year Efficacy and Safety Data in ISM (PRNewswire) - P2 | N=251 | PIONEER (NCT03731260) | Sponsor: Blueprint Medicines Corporation | "AYVAKIT 25 mg once daily (QD) was well-tolerated and no new safety signals were identified with a median of 3 years of exposure, with some patients out to five years of treatment. The most common treatment-related adverse events (AEs; ≥5 percent) were low-grade peripheral edema, periorbital edema, headache and nausea. AYVAKIT 25 mg QD led to robust and durable improvements in overall symptoms, individual symptom domains (skin, gastrointestinal, neurocognitive) and quality of life through 144 weeks of treatment. In patients who had high disease burden and escalated to AYVAKIT 50 mg QD (median follow-up: 10.6 months since escalation), treatment was well-tolerated, with side effects consistent with those reported at AYVAKIT 25 mg QD and no patients discontinuing due to AEs. Nearly all patients (93 percent) had improved or stable benefits in overall symptoms."

P2 data • Aggressive Systemic Mastocytosis

Avapritinib in the Treatment of Unresectable or Recurrent Metastatic GIST Non-exon18 Mutations of PDGFRA (clinicaltrials.gov) - P=N/A | N=74 | Recruiting | Sponsor: Xinhua Zhang, MD | Not yet recruiting ➔ Recruiting | Trial completion date: Aug 2024 ➔ Dec 2025 | Trial primary completion date: Aug 2024 ➔ Dec 2025

Enrollment open • Real-world evidence • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Solid Tumor • ANO1

A Multicenter Study of Avapritinib Efficacy and Safety of Metastatic or Unresectable Gastrointestinal Stromal Tumors (clinicaltrials.gov) - P=N/A | N=74 | Recruiting | Sponsor: Xinhua Zhang, MD | Not yet recruiting ➔ Recruiting | Trial completion date: Aug 2024 ➔ Dec 2025 | Trial primary completion date: Aug 2024 ➔ Dec 2025

Enrollment open • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Solid Tumor • ANO1

Avapritinib and Bone Health in Indolent Systemic Mastocytosis: Learnings from the PIONEER Trial (AAAAI-WAO 2025) - P2 | "Among enrolled patients, concomitant medications included bisphosphonates (9%), denosumab (4%), calcium (23%), and vitamin D (36%). Conclusions Osteoporosis and osteopenia are prevalent in ISM. These hypothesis-generating results examining the impact of avapritinib plus best supportive care on bone health in ISM provide an impetus for pursuing longitudinal follow-up studies assessing BMD in a larger cohort of ISM patients."

Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology

The Prospective Use of Avapritinib in Relapsed/Refractory (R/R) RUNX1-RUNX1T1-Positive AML Patients With KIT Mutation. (PubMed, Clin Lymphoma Myeloma Leuk) - No abstract available

Journal • Acute Myelogenous Leukemia • Bone Marrow Transplantation • KIT • RUNX1 • RUNX1T1

Avapritinib for the Treatment of CKIT or PDGFRA Mutation-Positive Locally Advanced or Metastatic Malignant Solid Tumors (clinicaltrials.gov) - P2 | N=50 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Feb 2025 ➔ Dec 2026 | Trial primary completion date: Feb 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Brain Cancer • Breast Cancer • CNS Tumor • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Lung Cancer • Melanoma • Oncology • Sarcoma • Solid Tumor • PDGFRA