PEAK

31 evidence topics · 15 sources

Objective

Randomized comparison after prior imatinib

“To determine the efficacy of bezuclastinib and sunitinib vs sunitinib in patients with GIST and prior imatinib only” (opens the source at this quote in a new tab)

Location and study date

Study initiation

“study started April 2022” (opens the source at this quote in a new tab)

Part 1 update cutoff

“April 1, 2024” (opens the source at this quote in a new tab)

Study design

Open-label international study and randomization

“open-label, international, multicenter study” (opens the source at this quote in a new tab)
“patients being randomized in a 1:1 manner.” (opens the source at this quote in a new tab)

Crossover after centrally confirmed progression

“Crossover allowed following BICR confirmed PD” (opens the source at this quote in a new tab)

Eligibility criteria

Histologic diagnosis and disease extent

“Histologically confirmed locally advanced, metastatic, and/or unresectable GIST.” (opens the source at this quote in a new tab)

Prior therapy for the randomized comparison

“Prior treatment with imatinib only” (opens the source at this quote in a new tab)

Excluded molecular subtypes

“Known Platelet-Derived Growth Factor Receptor (PDGFR) driving mutations or known succinate dehydrogenase deficiency” (opens the source at this quote in a new tab)

Treatment

Selected combination dose

“bezuclastinib 600 mg QD + sunitinib 37.5 mg QD” (opens the source at this quote in a new tab)

Control-arm daily dose

Treatment	Daily dose, mg
Sunitinib	“37.5”

Study outcomes

Rationale for using BICR-assessed progression-free survival as the primary endpoint

Primary and key secondary endpoints

Endpoint role	Endpoint
Primary	“Progression Free Survival per BICR”
Key secondary	“Objective Response Rate per BICR”
Key secondary	“Overall Survival”

Regulatory context for progression-free survival

“PFS can reflect tumor growth and be assessed before the determination of a survival benefit.” (opens the source at this quote in a new tab)
“Its determination is not confounded by subsequent therapy.” (opens the source at this quote in a new tab)

Statistical analysis description

Number of participants (Planned and analyzed)

Planned enrollment in the randomized part

“approximately 388 patients” (opens the source at this quote in a new tab)

Pivotal randomized population

“413 patients with advanced GIST who had received prior therapy with imatinib were randomized to either bezuclastinib plus sunitinib or sunitinib alone.” (opens the source at this quote in a new tab)

Part 1 treated population

Population	Participants
Part 1	“42”

Description of analysis sets

Summary

The pivotal response analysis reports 204 participants assigned to the combination and 209 assigned to sunitinib. The safety presentation uses 204 and 208 participants, respectively. These denominators should not be interchanged.

Part 1 safety analysis set

“Safety Analysis Set: All treated pts” (opens the source at this quote in a new tab)

Randomized-part safety population

Treatment	Participants
Bezuclastinib plus sunitinib	“204”
Sunitinib	“208”

Full statistical analysis plan

No evidence found.

Results

Participant disposition

Summary

One participant assigned to sunitinib did not receive treatment. In the Part 1 update, 31 of 42 participants had discontinued and 11 remained on study treatment.

Part 1 disposition

Disposition	Participants
Discontinued	“31”
Ongoing	“11”

Baseline characteristics

Pivotal population age

Characteristic	Value
Median age and range, years	“63 (30-88)”

Efficacy results

PEAK phase 3: progression-free survival

“mPFS, as assessed by blinded independent central review, was 16.5 months for the bezuclastinib combination vs. 9.2 months for sunitinib monotherapy.” (opens the source at this quote in a new tab)

Pivotal progression-free-survival treatment effect

“The combination reached a median progression free survival (mPFS) of 16.5 months compared to sunitinib monotherapy, which reached a mPFS of 9.2 months (HR=0.50, CI: 0.39-0.65; p<0.0001).” (opens the source at this quote in a new tab)

PEAK phase 3: objective response

Treatment arm	“ORR per BICR , %, n [95% CI]”
“Bezuclastinib + Sunitinib”“(n=204)”	“45.6%”“93 [38.6, 52.7]”
“Sunitinib”“(n=209)”	“25.8%”“54 [20.0, 32.3]”

PEAK phase 3: overall survival

“Data for overall survival remains immature.” (opens the source at this quote in a new tab)

Progression on subsequent therapy: endpoint definition

“the time from randomization to progression on the next line of therapy or death.” (opens the source at this quote in a new tab)

Progression on subsequent therapy: reported results

Measure	Value
Combination-arm median, months	“not reached”
Sunitinib-arm median, months	“21”
Hazard ratio	“0.57”
95% confidence interval	“0.41-0.78”

PEAK Part 1: subgroup with one prior treatment

“median progression free survival (mPFS) of 19.4-months and 33% ORR in subset of advanced GIST patients with one prior treatment” (opens the source at this quote in a new tab)

Health-related quality of life and patient-reported outcomes

No evidence found.

Safety results

PEAK phase 3: safety

“Grade 3+” (opens the source at this quote in a new tab)
“bezuclastinib combination vs. sunitinib” (opens the source at this quote in a new tab)
“Hypertension (29.4% vs. 27.4%), Neutropenia (15.2% vs. 15.4%), ALT/AST increased (10.8% vs. 1.4%), Anemia (9.3% vs. 4.8%)” (opens the source at this quote in a new tab)

PEAK phase 3: treatment discontinuation

“7.4% of patients on the bezuclastinib combination and 3.8% of patients on sunitinib monotherapy discontinued study treatment(s) due to treatment related adverse events.” (opens the source at this quote in a new tab)

Study limitations

Summary

PEAK was open-label, although progression-free survival was assessed by blinded independent central review. Crossover was permitted after centrally confirmed progression, and overall-survival results remained immature. The randomized comparison required prior imatinib only and excluded PDGFR-driven and succinate dehydrogenase-deficient disease. Part 1 subgroup results should not be treated as randomized estimates.