Discussion
pneumonia, rash, anemia, constipation
RESPIRATORY FAILURE, PNEUMONIA, ANEMIA
This phase II study showed that iruplinalkib (WX-0593) had favorable clinical efficacy and manageable safety profiles in patients with Iruplinalkib achieved the primary endpoint with an IRC-assessed ORR of 69.9% (95% CI 61.7–77.2%) whose lower limit of the 95% CI exceeded the pre-defined threshold of 40%. In this study, investigator-assessed ORR was 63.0% (95% CI 54.6–70.8%), consistent with data from the phase I study of iruplinalkib with an investigator-assessed ORR of 63.0% (95% CI 47.5–76.8%) in the dose-escalation phase and 58.2% (95% CI 47.4–68.5%) in the dose-expansion phase [Subgroup analysis of ORR in previous clinical studies was limited. Studies of alectinib and brigatinib reported the results in patients with or without previous chemotherapy. In patients with previous chemotherapy, ORRs were 44% for alectinib [In this study, the median DoR were 14.4 months (95% CI 13.1–NE) by IRC and 13.2 months (95% CI 10.4-17.7) by investigator, while the median DoR for ceritinib was 6.9 months by IRC [Several studies suggested that CNS progression occurred frequently within one year during crizotinib treatment [In this study, OS data were immature, with a median follow-up of 18.2 months (95% CI 16.8–18.8). Estimated 12-month and 24-month OS rates were 85.2% (95% CI 78.2–90.1%) and 57.9% (95% CI 44.2–69.4%), respectively. The 12-month OS rates for alectinib and brigatinib 180 mg, and 24-month OS rate for brigatinib 180 mg were 71% [In terms of RP2D, in the dose-expansion phase of the previous iruplinalkib phase I study, two patients who received iruplinalkib 120 mg orally once daily without the lead-in dose died due to infectious pneumonia and respiratory failure, which occurred within 48 h after iruplinalkib treatment initiation, respectively [For safety, TRAEs for iruplinalkib occurred in 93.2% patients, with a numerically lower incidence of anemia, constipation, and rash than alectinib [For PK analysis, mean CThis study has some limitations. The OS data were immature because of insufficient follow-up duration. Updated OS data were awaited. There was also a lack of detection of efficacy predictors before and resistance mutations after iruplinalkib treatment. These could be investigated in the further studies. Besides, this study only enrolled Chinese patients, thus caution must be paid when these results were interpreted for other ethnic patients.