(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

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.

The AdvSM-SAF is a 10-item questionnaire that assesses eight symptoms specific to AdvSM. All eight symptoms are scored on a scale of 0 (absence of symptoms) to 10 (more severe symptoms) (up to 80 points maximum). Each symptom contributes to the TSS equally. The TSS was generated based on average scores for each 7-day period. An increase in score from 0 (no symptoms) to 80 (worst symptoms represents a worse symptoms outcome. Participants completed the AdvSM-SAF daily using an electronic diary (eDiary). Each cycle is 28 days long.

ORR was defined as the percentage of participants with a confirmed best response of CR, CRh, PR, or 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.

TTR was defined as the time from first dose to the time of initial evaluation of clinical improvement (CI) or better. Here, 'Overall Number of Participants Analyzed' signifies those participants with a confirmed best response of CR, CRh, PR, and CI by mIWG-MRT-ECNM criteria.

DOR was defined as the time from initial documentation of a CI or better to the time of initial documentation of confirmed progressive disease (PD) or death due to any cause, whichever occurred first. For responders who had not progressed or died at the time of analysis, DOR was censored at the last response assessment that was stable disease (SD) or better. Here, 'Overall Number of Participants Analyzed' signifies those participants with a confirmed best response of CR, CRh, PR, and CI by mIWG-MRT-ECNM criteria.

PFS was defined as time from first dose to the time of initial documentation of confirmed PD or death due to any cause, whichever occurred first. Participants who had not progressed or died at the time of analysis were censored at the last response assessment that was SD or better.

OS was defined as time from first dose to the time of death due to any cause. Participants who were known to be alive or are lost to follow-up were censored at the last time point they were known to be alive.

The objective response rate was defined as the number of participants with a confirmed best response of morphologic complete remission, morphologic complete remission with partial recovery of peripheral blood counts, or morphologic partial remission by pure pathologic response (PPR) criteria. The PPR criteria are a modification of the mIWG-MRT-ECNM criteria that define deep responses where direct measure of the disease burden determined the response and focus on objective changes (bone marrow mast cell burden, serum tryptase, and complete blood count).

The clinical benefit rate was defined as the percentage of participants with a confirmed best response of CR, CRh, PR, CI, and SD by mIWG-MRT-ECNM criteria.

Bone marrow biopsies and aspirates and peripheral blood smears were obtained for systemic mastocytosis response assessment according to mIWG-MRT-ECNM criteria. Each cycle is 28 days long.

Blood samples were collected to characterize the change in serum tryptase concentration during treatment with avapritinib. Each cycle is 28 days long.

Bone marrow aspirate and PB samples were collected to characterize the KIT D816V mutation allele fraction. Each cycle is 28 days long.

Assessment of liver volume was performed using serial imaging with magnetic resonance imaging (MRI). Response was defined as resolution of palpable hepatomegaly (CR). Each cycle is 28 days long.

Assessment of spleen volume was performed using serial imaging with MRI. Response was defined as ≥35% reduction in spleen volume (PR) or resolution of palpable splenomegaly (CR). Each cycle is 28 days long.

The AdvSM-SAF is a 10-item questionnaire that assesses symptoms and functional domains specific to AdvSM. Eight symptoms are scored on a scale of 0 to 10 for severity and 2 symptoms (vomiting and diarrhea) are scored for number of episodes. The skin domain is scored on a scale of 0-30, where 0 represents an absence of symptoms and 30 the most severe symptom experience. Similarly, the gastrointestinal domain is scored on a scale of 0-40, where 0 represents an absence of symptoms and 40 the most severe symptom experience. Skin and gastrointestinal domain scores were generated based on average scores for each 7-day period. An increase in score represents a worse symptoms outcome. Participants completed the AdvSM-SAF daily using an eDiary.

The AdvSM-SAF is a 10-item questionnaire that assesses symptoms and functional domains specific to AdvSM. Individual symptom scores are generated based on average scores for each 7-day period. Eight symptoms are scored on a scale of 0 to 10 for severity. An increase in score represents a worse symptoms outcome. Participants completed the AdvSM-SAF daily using an eDiary.

The AdvSM-SAF is a 10-item questionnaire that assesses symptoms and functional domains specific to AdvSM. Individual symptom scores are generated based on average scores for each 7-day period. Two symptoms (vomiting and diarrhea) are scored for number of episodes. An increase in score represents a worse symptoms outcome. Participants completed the AdvSM-SAF daily using an eDiary.

The PGIS is a single-item scale that assesses a participant's perception of disease symptoms at a point in time. Scores range from 0 to 4 points, with higher values representing worse symptom outcomes. It is widely used to evaluate a participant's overall sense of whether a treatment has been beneficial. Each cycle is 28 days long.

Quality of life was assessed using EORTC QLQ-C30, which is a 30-item questionnaire that includes 5 functional domains (physical, cognitive, role, emotional, and social) and a global health status scale. Twenty-eight questions are scored from 1 (not at all) to 4 (very much), while the other 2 are scored from 1 (very poor) to 7 (excellent). The calculated average is standardized using a linear transformation to a standardized scale of 0 to 100, with a decrease in score representing a decrease in quality of life. Each cycle is 28 days long.

A TEAE was defined as any adverse events that occurred between the first dose of a study drug through 30 days after the last dose of any study drug. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.

Blood samples were collected at specified timepoints. Results reported as nanograms/milliliter (ng/mL).

The change in baseline for AdvSM-SAF TSS was correlated with the change in baseline for serum tryptase. Spearman correlation coefficients were performed with corresponding scatter plots on change from baseline.