SUMMIT

32 evidence topics · 22 sources

Objective

Comparison of safety and efficacy

“comparing the safety and efficacy” (opens the source at this quote in a new tab)

Location and study date

SUMMIT Part 2 primary analysis: data cutoff

“Data cutoff: May 22, 2025.” (opens the source at this quote in a new tab)

European study participation

“In addition, bezuclastinib, another TKI specific to D816V, is being evaluated in a study (SUMMIT) involving several European centers” (opens the source at this quote in a new tab)

Study design

SUMMIT NCT05186753: study design

“This is a multi-part, randomized, double-blind, placebo-controlled Phase 2 clinical study” (opens the source at this quote in a new tab)

SUMMIT Part 2: randomization

“randomized 2:1” (opens the source at this quote in a new tab)

Eligibility criteria

SUMMIT Part 2: symptom-based eligibility

“Inadequate symptom control (moderate to severe symptoms) despite ≥2 anti-mediator therapies” (opens the source at this quote in a new tab)

Avapritinib-switch substudy: population

“patients who are experiencing inadequate symptom control with avapritinib.” (opens the source at this quote in a new tab)

Treatment

SUMMIT Part 2: bezuclastinib dose

“100mg every day” (opens the source at this quote in a new tab)

SUMMIT Part 2: background therapy in both randomized groups

“bezuclastinib+ BSC” (opens the source at this quote in a new tab)
“placebo+BSC” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using MS2D2 total symptom score as the primary endpoint

Primary symptom endpoint

“24-week mean change from baseline in Mastocytosis Symptom Severity Daily Diary (MS2D2) total symptom score (TSS)” (opens the source at this quote in a new tab)

Outcome-instrument validation: MS2D2

“Test–retest reliability between screening and baseline among PGIS-stable participants indicated excellent agreement (ICC > 0.9) for all MS2D2 scores” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

SUMMIT Part 2: randomized treatment groups

“n=119 bezuclastinib, n=60 placebo;” (opens the source at this quote in a new tab)

SUMMIT Part 1a: enrollment

“Part 1a of Summit enrolled 20 patients” (opens the source at this quote in a new tab)

Description of analysis sets

Biomarker responder analysis: intention-to-treat handling of missing observations

“ITT population: patients missing data at baseline and/or week 24 are treated as nonresponders for this analysis.” (opens the source at this quote in a new tab)

Exploratory individual-symptom analysis: covariates and multiplicity

“Unadjusted P values based on ANCOVA model adjusted for TSS baseline and tryptase level, no multiplicity adjustment.” (opens the source at this quote in a new tab)

Results

Participant disposition

SUMMIT Part 2: withdrawal before treatment

“One patient withdrew consent and did not receive treatment.” (opens the source at this quote in a new tab)

Avapritinib-switch extension: anticipated results

“preliminary results expected by end of 2026.” (opens the source at this quote in a new tab)

Baseline characteristics

SUMMIT Part 2: baseline age

Baseline median age in years, with range	Direct quotation
Bezuclastinib	“51 (24–73)”
Placebo	“52 (23–78)”

SUMMIT Part 2: baseline symptom burden and smoldering subtype

Characteristic	Bezuclastinib	Placebo
Mean baseline MS2D2 TSS	“57.1”	“52.6”
Participants with smoldering SM	“8”	“4”

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

“Outcome measure”	“Bezuclastinib”	“Placebo”	“p-value”
“≥50% reduction in TSS”	“34.3%”	“18.1%”	“p=0.01”
“≥30% reduction in TSS”	“65.4%”	“38.6%”	“p<0.001”

SUMMIT Part 2: serum tryptase at 24 weeks

“Patients reaching ≥50% reduction in serum tryptase at 24 weeks, % (n/N)” (opens the source at this quote in a new tab)

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 Part 1b: symptom severity at 12 weeks

“Patients treated with 100 mg bezuclastinib reported a significant reduction in total symptom severity vs. placebo at Week 12 (-23.78 vs. -9.03; p=0.0003)” (opens the source at this quote in a new tab)

SUMMIT selected 100 mg dose and open-label extension: 12-week assessment

“Pts treated with 100 mg bezu had reduction in MS2D2 TSS by 49.1% vs 21.1% with PBO.” (opens the source at this quote in a new tab)

SUMMIT Part 1: 48-week follow-up

“MS2D2 Total Symptom Score reduced from baseline by a mean of 28.8 points and 64.6% at 48 weeks” (opens the source at this quote in a new tab)

SUMMIT Part 2: exploratory bone assessments

“Patients receiving bezuclastinib demonstrated increased spine BMD at Week 24, while those receiving placebo showed no improvement or a decrease” (opens the source at this quote in a new tab)

SUMMIT: correlation between symptom improvement and objective disease markers

“Symptom improvement significantly correlated with serum tryptase reduction” (opens the source at this quote in a new tab)
“p < 0.001, r = 0.39” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

SUMMIT selected 100 mg dose: 12-week MC-QoL change

Measure	Bezuclastinib 100 mg	Placebo
Least-squares mean change from baseline	“-22.05”	“-10.71”

Safety results

SUMMIT Part 2: selected treatment-emergent adverse events

“hair color change (69.5% bezuclastinib vs. 5.0% placebo)” (opens the source at this quote in a new tab)
“ALT/AST elevations (22.0% bezuclastinib vs. 6.6% placebo; ≥Gr 3, 5.9% vs. 0%)” (opens the source at this quote in a new tab)

SUMMIT Part 2: treatment-related discontinuations

“All discontinuations (5.9%) due to treatment-related AEs were due to transaminase elevations; all fully resolved.” (opens the source at this quote in a new tab)

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.