Bezuclastinib

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.

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.

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.

The design used a one-sample log-rank calculation with a one-sided 5% significance level. Thirty-five evaluable participants provided 83% power for an assumed median progression-free survival of 6.5 months compared with a 4-month historical benchmark. This is a historical-control calculation, not a randomized comparison.

SARC044 is a single-arm, open-label phase 2 study with planned enrollment of up to 40 participants. Its statistical comparison uses a historical progression-free-survival benchmark rather than a concurrently randomized control. Eligibility primarily specifies KIT exon 9- or 11-mutant GIST, with other primary KIT mutations considered case by case. The enrollment-completion announcement does not establish efficacy or safety results.

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.

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.

The trial was unblinded early after a planned interim analysis showed a longer time to progression with sunitinib.

The randomized trial was unblinded early after its planned interim analysis. Its primary endpoint was time to tumor progression rather than progression-free survival, which also counts deaths. The comparison was sunitinib against placebo, not bezuclastinib plus sunitinib against sunitinib.

Participants were randomized to morning or evening administration of continuous daily sunitinib. This was a comparison of administration times, not of sunitinib against another drug.

The primary clinical benefit rate combined complete responses, partial responses, and stable disease lasting at least 24 weeks.

The study treated 60 participants and was open-label. Randomization compared morning and evening dosing rather than continuous dosing against the intermittent schedule or against another therapy. The clinical benefit endpoint included prolonged stable disease, which is not equivalent to objective tumor response.

The monotherapy and sunitinib-combination cohorts used nonrandomized 3+3 dose escalation.

The early-trial recommended phase 2 dose was PLX9486 1000 mg daily, combined with sunitinib 25 or 37.5 mg daily in continuous 28-day cycles.

Sample sizes reflected clinical considerations. Response intervals used exact binomial methods, and survival analyses used Kaplan-Meier methods.

Three monotherapy participants were reenrolled in the extension, producing a safety population of 18 without increasing unique enrollment.

The combination efficacy cohort included 15 PLX9486-naive participants. Nonrandomized treatment assignment, small sample size, and disease heterogeneity limit comparative interpretation.