Retrospective Study Assessing the Effect of Avapritinib Versus Best Available Therapy in Patients With AdvSM

Study Overview
=================
Brief Summary
-----------------
BLU-285-2405 is a multi-center, synthetic control, observational and retrospective study designed to compare clinical outcomes for avapritinib compared with best available therapy for patients with AdvSM.

Official Title
-----------------
An External Control, Observational, Retrospective Study Assessing the Effect of Avapritinib Compared With Best Available Therapy for Patients With Advanced Systemic Mastocytosis

Conditions
-----------------
Advanced Systemic Mastocytosis, Aggressive Systemic Mastocytosis, Systemic Mastocytosis With an Associated Hematological Neoplasm, Mast Cell Leukemia

Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria for Patients in the External Control Arm: Diagnosed with AdvSM, with known subtype including SM-AHN, ASM, or MCL Received at least one line of systemic therapy for AdvSM, which may include but not limited to regimens containing: Midostaurin Cytoreductive therapy: cladribine, interferon alpha, azacitidine, decitabine Selective TKIs: imatinib, nilotinib, dasatinib Hydroxyurea Antibody therapy: brentuximab vedotin Adult (≥18 years of age) at the initiation of first systemic line of therapy at the participating site Had an index date at least 3 months prior to the start of data collection (in order to include patients with at least 3 months of follow-up after index date), unless date of death occurred less than three months from index date Had an approved waiver of informed consent or signed informed consent for participation in the retrospective chart review study, if no institutional waiver from the site was granted Exclusion Criteria for Patients in the External Control Arm Malignancy that is not in remission at time of SM diagnosis, or new non-hematological malignancy diagnosed after SM diagnosis, except for: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site Among patients with SM-AHN, presence of either of the following: Patients in whom the SM component is consistent with an indolent systemic mastocytosis (ISM) or SSM or, the AHN component is a lymphoid malignancy, or one of the following myeloid malignancies: acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) that is very high-or high-risk as defined by the IPSS-R, or a Philadelphia chromosome positive malignancy or, there is a known FIP1L1/PDGFRA fusion gene (including those with CHIC-2 deletion and partial deletion of PDGFRA), independent of KIT mutational status Received avapritinib as the first line of systemic therapy for AdvSM at participating site, or prior to initiation of first systemic therapy at participating site.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients from the BLU-285-2101 and BLU-285-2202 studies<br>Patients with advanced systemic mastocytosis who received treatment with avapritinib as part of the BLU-285-2101 and BLU-285-2202 studies | |
| External Control Group<br>Patients with advanced systemic mastocytosis that received best available therapy | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparative evaluation of overall survival (OS) between patients receiving best available therapy versus avapritinib in BU-285-2101 and BLU-285-2202 | Overall Survival defined as time from initiation of systemic treatment to death from any cause | up to 12 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparative evaluation between patients receiving best available therapy versus avapritinib of duration of treatment (DOT) | DOT, defined as the duration from initiation of line of systemic treatment to discontinuation of same line of treatment for any reason and; | Up to 12 years | 
| Comparative evaluation between patients receiving best available therapy versus avapritinib and time to next treatment line (TtNTL) | TtNTL, defined as the time from initiation of the line of systemic treatment to the initiation of the next line of treatment | Up to 12 years | 
| Comparative evaluation of change in serum tryptase concentration in patients receiving best available therapy versus avapritinib | Change in serum tryptase concentration, defined as change in serum tryptase from baseline, for each line of therapy | Up to 12 years | 
| To characterize the safety profile and conduct comparative evaluation of safety between patients receiving best available therapy vs. avapritinib | AEs that result in treatment modification or discontinuation, hospitalization, or death according to evaluation of responsible physician | Up to 12 years |