Section 4 of 6
Clinical evidence
61 evidence topics · 27 sources
Study summaries
SUMMIT
Objective
Comparison of safety and efficacy
Location and study date
SUMMIT Part 2 primary analysis: data cutoff
Study design
SUMMIT Part 2: randomization
Eligibility criteria
SUMMIT Part 2: symptom-based eligibility
Avapritinib-switch substudy: population
Treatment
SUMMIT Part 2: bezuclastinib dose
SUMMIT Part 2: background therapy in both randomized groups
Study outcomes
Rationale for using MS2D2 total symptom score as the primary endpoint
Statistical analysis description
Number of participants (Planned and analyzed)
SUMMIT Part 2: randomized treatment groups
SUMMIT Part 1a: enrollment
Description of analysis sets
Biomarker responder analysis: intention-to-treat handling of missing observations
Exploratory individual-symptom analysis: covariates and multiplicity
Results
Participant disposition
SUMMIT Part 2: withdrawal before treatment
Avapritinib-switch extension: anticipated results
Baseline characteristics
SUMMIT Part 2: baseline age
| Baseline median age in years, with range | Direct quotation |
|---|---|
| Bezuclastinib | “51 (24–73)” |
| Placebo | “52 (23–78)” |
Efficacy results
SUMMIT Part 2: primary endpoint, 24-week total symptom score
| Measure | Bezuclastinib | Placebo | Statistical significance |
|---|---|---|---|
| TSS, “mean reduction”, points | “24.3” | “15.4” | “p=0.0002” |
SUMMIT Part 2: symptom-response endpoints at 24 weeks
SUMMIT Part 2: serum tryptase at 24 weeks
| Population | Bezuclastinib | Placebo | Statistical significance |
|---|---|---|---|
| “ITT population” | “87.4 (104/119)” | “0 (0/60)” | “P<0.0001” |
SUMMIT Part 2: 48-week follow-up, November 2025 cutoff
| Measure | Bezuclastinib |
|---|---|
| “Mean change TSS (%)” | “-32.0 (-54%)” |
SUMMIT selected 100 mg dose and open-label extension: 12-week assessment
SUMMIT: correlation between symptom improvement and objective disease markers
Health-related quality of life and patient-reported outcomes
Safety results
SUMMIT Part 2: treatment-related discontinuations
Study limitations
Summary
SUMMIT compares bezuclastinib with placebo rather than an active KIT inhibitor. Eligibility requires inadequate symptom control despite at least two anti-mediator therapies, limiting direct applicability to less symptomatic or untreated populations. Baseline mean TSS was 57.1 versus 52.6, and the smoldering SM groups contained only 8 and 4 participants. Reported subgroup changes are within-arm estimates rather than treatment-by-subgroup interaction tests. The individual-symptom analyses report no multiplicity adjustment. Biomarker responder analyses count missing baseline or week 24 observations as nonresponse; those rules should not be assumed to describe every efficacy analysis.
PIONEER
Objective
Comparator trial objective
Location and study date
Long-term follow-up: data cutoff
Study design
Randomized comparison: masking and control
Eligibility criteria
Symptom severity at enrollment
Minimum baseline total symptom score
| Eligibility measure | Threshold |
|---|---|
| TSS | “≥28” |
Treatment
Background treatment in both groups
Study outcomes
Rationale for using ISM-SAF total symptom score as the primary endpoint
Primary endpoint: symptom assessment and averaging period
Statistical analysis description
Number of participants (Planned and analyzed)
Description of analysis sets
FDA label analysis: missing continuous symptom-score observations
Results
Participant disposition
Long-term analysis across PIONEER study parts
Baseline characteristics
Efficacy results
Comparator avapritinib, PIONEER trial: week 24 total symptom score, avapritinib
Comparator avapritinib, PIONEER trial: week 24 total symptom score, placebo
Comparator avapritinib, PIONEER trial: abstract-reported statistical significance
Health-related quality of life and patient-reported outcomes
Safety results
Comparator avapritinib, PIONEER long-term follow-up
Study limitations
Summary
PIONEER evaluates avapritinib, not bezuclastinib, in moderate-to-severe ISM. Its results do not provide a head-to-head comparison of the two drugs. The publication and FDA label report different numerical TSS analyses, which are preserved separately. Long-term Part 3 is open-label. The Canadian appraisal reports only two versus three post-baseline anaphylaxis events treated with epinephrine, limiting the precision of conclusions about that outcome.
WO2024138005A1 example 7
Objective
Formulation comparison objective
Location and study date
No evidence found.
Study design
Single-center crossover formulation comparison
Eligibility criteria
Treatment
Study outcomes
Rationale for using pharmacokinetics and relative bioavailability as the study endpoints
Not applicable.
Statistical analysis description
Number of participants (Planned and analyzed)
Participants receiving the three initial dose levels
Description of analysis sets
No evidence found.
Results
Participant disposition
No evidence found.
Baseline characteristics
No evidence found.
Efficacy results
Health-related quality of life and patient-reported outcomes
Not applicable.
Safety results
Study limitations
Summary
The formulation comparison included 30 healthy-adult participants in a single-center, open-label crossover study. These single-dose pharmacokinetic observations do not establish efficacy or long-term safety in nonadvanced SM. The source does not disclose a trial acronym or protocol number; the study is identified here by the patent's Example 7.