INTRIGUE

21 evidence topics · 6 sources

Objective

Comparative safety and efficacy

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

Location and study date

International study sites

Measure	Number
Sites	“122”
Countries	“22”

Final overall-survival data cutoff

“March 15, 2023” (opens the source at this quote in a new tab)

Study design

Randomized phase 3 design

“global, randomized (1:1), open-label, Phase III study” (opens the source at this quote in a new tab)

Crossover restriction

“Crossover was not allowed.” (opens the source at this quote in a new tab)

Eligibility criteria

Prior systemic treatment

“previously treated with imatinib” (opens the source at this quote in a new tab)

Treatment

Randomized treatment doses

Treatment	Oral dose
Ripretinib	“150 mg once daily”
Sunitinib	“50 mg once daily”

Sunitinib treatment schedule

“4 weeks on/2 weeks off” (opens the source at this quote in a new tab)

Study outcomes

Rationale for using progression-free survival as the primary endpoint

Primary and key secondary endpoints

Endpoint role	Endpoint
Primary	“progression-free survival”
Key secondary	“objective response rate”
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)

Statistical analysis description

Number of participants (Planned and analyzed)

Randomized population

“Overall, 453 patients were randomly assigned” (opens the source at this quote in a new tab)

Description of analysis sets

Summary

Efficacy analyses used the intention-to-treat population. Safety analyses included participants who received at least one dose. The testing hierarchy evaluated progression-free survival, then response rate, then overall survival, with KIT exon 11 analyses preceding overall-population analyses. Failure of the primary comparison meant subsequent statistical comparisons were not confirmatory.

Reported analysis populations

“ITT population” (opens the source at this quote in a new tab)

Results

Participant disposition

Randomized treatment allocation

Treatment	Participants
Ripretinib	“226”
Sunitinib	“227”

Baseline characteristics

Overall baseline characteristics

Characteristic	Value
Median age, years	“60”
Male participants, percent	“62.0%”

Efficacy results

Primary progression-free-survival comparison

“Ripretinib was not superior to sunitinib in terms of PFS.” (opens the source at this quote in a new tab)

Overall-population progression-free survival

Measure	Ripretinib	Sunitinib
Median progression-free survival, months	“8.0”	“8.3”

Final overall-survival analysis

Comparison	Median overall survival
Ripretinib versus sunitinib	“35.5 v 31.5 months”

Health-related quality of life and patient-reported outcomes

Patient-reported tolerability with ripretinib versus sunitinib

“better scores on patient-reported outcome measures of tolerability.” (opens the source at this quote in a new tab)

Safety results

Grade 3 or 4 treatment-emergent adverse events

Measure	Ripretinib	Sunitinib
Participants with events	“41.3%”	“65.6%”

Study limitations

Summary

The open-label study did not show superiority of ripretinib for its primary progression-free-survival comparison. Safety percentages describe treatment-emergent events and should not be equated with treatment-related-event percentages from other trials. Neither randomized arm contained bezuclastinib.