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Label indication AYVAKIT is a kinase inhibitor indicated for: Gastrointestinal Stromal Tumor (GIST) the treatment of adults with unresectable or metastatic GIST harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations. ( 1.1 , 2.2 ) Advanced Systemic Mastocytosis (AdvSM) the treatment of adult patients with AdvSM. FDA label
Also known as Ayvakit, BLU-285
Avapritinib · 8 trials · 16 indications
To demonstrate the efficacy of avapritinib based on progression-free survival (PFS) determined by central radiological assessment per modified Response Evaluation Criteria in Solid Tumors (mRECIST), version 1.1 in patients with advanced GIST following 2 or 3 regimens of prior treatment with a tyrosine kinase inhibitor (TKI), including imatinib, compared to patients treated with regorafenib. A progressively growing tumor must meet the following criteria: a) the target lesions must be greater or equal to 2cm in size and be a new GIST active lesion or b) the target lesions must be expanding on at least 2 sequential imaging studies.
0 - 110 points (higher value represents worse symptom outcomes)
ORR was defined as the percentage of participants with a confirmed best response of complete remission (CR), complete remission with partial recovery of peripheral blood counts (CRh), partial remission (PR), or clinical improvement (CI) by mIWG-MRT-ECNM criteria. The mIWG-MRT-ECNM criteria were based on findings from bone marrow biopsy and aspirate, and peripheral blood smear; bone marrow cytogenetics; other extracutaneous tissue biopsies (when available); liver and spleen imaging; and other clinical and laboratory parameters.
Recommended phase 2 dose which will be determined by evaluating all safety and efficacy data.
Patients with event(s) of dose-limiting toxicity
The overall safety profile of the drug was assessed by reviewing the number of patients with AEs, SAEs and other events. There was no formal statistical analysis. Safety assessments continued for the duration of treatment.
To evaluate objective response rate (ORR) determined by central radiology assessment per mRECIST, version 1.1 in patients with advanced GIST treated with avapritinib. A complete response per modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) is defined as complete disappearance of all target lesions. A partial response is defined as at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters. Overall Response (OR) = CR + PR
| Arm | Type | Description |
|---|---|---|
| avapritinib | EXPERIMENTAL | 300 mg PO QD |
| regorafenib | ACTIVE_COMPARATOR | 160 mg PO QD |
| (Part 1) Avapritinib Dose 1 + BSC | EXPERIMENTAL | Avapritinib will be administered orally in continuous 28-day cycles |
| (Part 1) Avapritinib Dose 2 + BSC | EXPERIMENTAL | Avapritinib will be administered orally in continuous 28-day cycles |
| (Part 1) Avapritinib Dose 3 + BSC | EXPERIMENTAL | Avapritinib will be administered orally in continuous 28-day cycles |
| (Part 1) Placebo + BSC | PLACEBO_COMPARATOR | Placebo will be administered orally in continuous 28-day cycles |
| (Part 2) Avapritinib RP2D + BSC | EXPERIMENTAL | Avapritinib will be administered orally in continuous 28-day cycles |
| (Part 2) Placebo + BSC | PLACEBO_COMPARATOR | Placebo will be administered orally in continuous 28-day cycles |
| (Part 3) Avapritinib RP2D + BSC | EXPERIMENTAL | Avapritinib will be administered orally in continuous 28-day cycles |
| Dose Escalation | EXPERIMENTAL | Participants will be enrolled in cohorts of size 1-3. Participants will take a combination of Avapritinib and Decitabine. Decitabine will be administered in one of the following forms: I) Decitabine: starting IV dose of 20 mg/m2 on days 1-5 of a 28-day treatment cycle. II) Decitabine/Cedazuridine: starting dose of 35mg/100 mg oral tablet on days 1-5 of a 28-day treatment cycle. The starting dose of Avapritinib for the first cohort of patients will begin at dose level 1 with dose modifications to be made according to a Bayesian design. Avapritnib Dose levels Level -1: 50mg Level 1: 100mg Level 2: 150mg Level 3: 200mg |
| Dose Expansion | EXPERIMENTAL | Participants with baseline platelet count (cycle 1, day 1) ≥ 75 x 10\^9/L will begin the combination of Avapritinib at the dose determined by the dose-finding portion of the study and decitabine or Decitabine/Cedazuridine will be initiated during the first cycle. Participants with a baseline platelet count between 25 x 10\^9/L and 74 x 10\^9/L will receive decitabine or Decitabine/Cedazuridine (choice of investigator) as a single-agent for at least the first two cycles. Starting with cycle 3 and continuing with each subsequent cycle, patients will be eligible to receive Avapritinib in combination with decitabine or Decitabine/Cedazuridine if the platelet count on day 1 of the cycle is ≥ 75 x 10\^9. If the platelet count is \< 75 x 10\^9/L on day 1 of the cycle, patient will receive single-agent Decitabine or Decitabine/Cedazuridine. In the absence of clear disease progression, patients will be treated for at least 6 cycles before being judged to have not responded. |
| Participants with metastatic, unresectable GIST, non-CNS solid tumors, or CNS tumors | EXPERIMENTAL | Participants will receive 5 mg of midazolam orally on Day 1 and Day 17. Participants will receive avapritinib 300 mg daily, orally on starting on Day 3. Participants with CNS tumors will receive avapritinib 300 mg daily orally, until Day 56. |
| Avapritinib (also known as BLU-285) | EXPERIMENTAL | Avapritinib tablets for oral administration. Avapritinib will be dosed daily for 28 day cycles. |
| Part 1 Avapritinib (formerly BLU-285) 30 mg QD | EXPERIMENTAL | Part 1: Patients received a starting dose of 30 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued. Patients received avapritinib in continuous 28 day cycles until discontinuation. |
| Part 1 Avapritinib (formerly BLU-285) 60 mg QD | EXPERIMENTAL | Part 1: Patients received a starting dose of 60 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued. Patients received avapritinib in continuous 28 day cycles until discontinuation. |
| Part 1 Avapritinib (formerly BLU-285) 90 mg QD | EXPERIMENTAL | Part 1: Patients received a starting dose of 90 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued. Patients received avapritinib in continuous 28 day cycles until discontinuation. |
| Part 1 Avapritinib (formerly BLU-285) 135 mg QD | EXPERIMENTAL | Part 1: Patients received a starting dose of 135 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued. Patients received avapritinib in continuous 28 day cycles until discontinuation. |
| Part 1 Avapritinib (formerly BLU-285) 200 mg QD | EXPERIMENTAL | Part 1: Patients received a starting dose of 200 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued. Patients received avapritinib in continuous 28 day cycles until discontinuation. . |
| Part 1 Avapritinib (formerly BLU-285) 300 mg QD | EXPERIMENTAL | Part 1: Patients received a starting dose of 300 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued. Patients received avapritinib in continuous 28 day cycles until discontinuation. Patients that received at least one dose of avapritinib were included in the Part 2 analysis. |
| Part 1 Avapritinib (formerly BLU-285) 400 mg QD | EXPERIMENTAL | Part 1: Patients received a starting dose of 400 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued. Patients received avapritinib in continuous 28 day cycles until discontinuation. Patients that received at least one dose of avapritinib were included in the Part 2 analysis. |
| Part 1 Avapritinib (formerly BLU-285) 600 mg QD | EXPERIMENTAL | Part 1: Patients received a starting dose of 600 mg QD for 28 days and they were assessed for dose limiting toxicities (DLT). If no DTLs were observed the dose escalation continued. Patients received avapritinib in continuous 28 day cycles until discontinuation. |
| Part 1 and Part 2 Avapritinib (formerly BLU-285) 300 mg or 400 mg QD | EXPERIMENTAL | Part 1 and Part 2: Patients enrolled in Part 1 and Part 2 at a starting dose of 300 or 400 mg QD were included in the Part1/Part 2 safety and efficacy analysis. Patients received avapritinib in continuous 28 day cycles until discontinuation. |
| Name | Type | Description |
|---|---|---|
| avapritinib | DRUG | Avapritinib tablets for oral administration. Avapritinib will be dosed at 300 mg once daily, continuously. |
| regorafenib | DRUG | Regorafenib tablets for oral administration. Regorafenib will be dosed at 160 mg once daily for 3 weeks out of every 4 weeks (ie. 3 weeks on/1 week off). |
| Placebo | DRUG | Placebo tablet |
| Decitabine | DRUG | Decitabine is a nucleoside metabolic inhibitor given intravenously. |
| Decitabine/Cedazuridine | COMBINATION_PRODUCT | Decitabine/Cedazuridine is a combination medicine given orally. |
| midazolam | DRUG | midazolam syrup |
Inclusion Criteria: 1. Patients who are ≥ 18 years of age. 2. Patients who have histologically confirmed metastatic or unresectable GIST. 3. Patients who received imatinib and 1 or 2 other TKIs as prior treatment regimens. Patients who experienced intolerance to prior therapies must have objective ...
Avapritinib is an investigational small molecule studied in advanced systemic mastocytosis, aggressive systemic mastocytosis, indolent systemic mastocytosis, gastrointestinal stromal tumors (GIST), and KIT- or PDGFRA-dependent pediatric solid tumors. It is being developed by Blueprint Medicines Corporation (ticker: BPMC) for rare disease indications.
Avapritinib targets PDGFRA and KIT, which are receptor tyrosine kinases. It is classified as an inhibitor of these targets. By inhibiting mutant forms of KIT and PDGFRA, it aims to block signaling pathways that drive certain mastocytosis and GIST tumors.
Avapritinib is developed by Blueprint Medicines Corporation, which trades under the ticker BPMC. The company is responsible for the clinical development of the drug across its studied indications.
Avapritinib is in Phase 2 clinical development. It is an investigational agent and has not been approved by the FDA for the indications described. The Phase 2 PIONEER trial (NCT03731260) evaluated avapritinib versus placebo in indolent systemic mastocytosis and is active but not recruiting.
Avapritinib has been studied in several trials, including NCT06327685, a Phase 1 study of avapritinib with decitabine in systemic mastocytosis with an associated hematologic neoplasm, which is recruiting. Other trials include NCT04908176, a completed drug-drug interaction study, NCT04773782, a completed Phase 1 pediatric solid tumor study, and the Phase 2 PIONEER trial NCT03731260.
Yes, Avapritinib is also known as BLU-285. The PIONEER study title refers to avapritinib (BLU-285), confirming that BLU-285 is an alternative name for the same drug.