This is a Phase I, multicenter, non-randomized, open-label, dose-exploratory clinical study to evaluate the safety and tolerability of linperlisib combined with SHR2554 in the treatment of R/R PTCL, and to preliminary observe the antitumor efficacy of the combination of the two drugs.
Linperlisib doses were preset at 40mg QD and 60mg QD, while SHR2554 doses were preset at 150mg BID, 200mg BID, and 300mg BID, forming six dose groups in total. The BOIN Waterfall design was employed to divide these six groups into two sub-trials. Initially, three participants will be recruited into the lowest dose group of the first sub-trial: Linperlisib (40mg QD) and SHR2554 (150mg BID). After completing the dose-limiting toxicity (DLT) observation period, the next dose group will begin. Once DLT evaluations for the three participants are completed, the statistician will review the safety data and, following the decision-making flowchart of the BOIN design, determine whether to escalate to the next dose level. Another three participants will be enrolled and evaluated, continuing this process until all dose combinations in the first sub-trial have been tested, the sample size is depleted, or a stopping rule is triggered. Based on the results of the first sub-trial, the statistician will assess and select the starting dose for the second sub-trial, repeating the process until the trial is complete.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
33
Linperlisib doses were preset at 40mg QD and 60mg QD, while SHR2554 doses were preset at 150mg BID, 200mg BID, and 300mg BID, forming six dose groups in total.
Maximum Tolerated Dose (MTD) of linperlisib in combination with SHR2554
MTD will be established according to the incidence of dose-limiting toxicities (DLTs)
Time frame: 28 days since the date of first dose
Safety of linperlisib in combination with SHR2554
The incidence and severity of treatment-emergent AEs will be collected and the safety and tolerability of linperlisib in combination with SHR2554 will be assessed.
Time frame: From the start of treatment until 30 days after the last treatment
Overall response rate (ORR)
Assess the response rate of subjects to the treatment of linperlisib in combination with SHR2554
Time frame: 2 years
Complete response (CR) rate
Assess the complete response rate of subjects to the treatment of linperlisib in combination with SHR2554
Time frame: 2 years
Progression-free survival (PFS)
Assess the survival condition of the subjects after the treatment of linperlisib in combination with SHR2554
Time frame: 2 years
Overall survival (OS)
Assess the overall survival of subjects treated by linperlisib in combination with SHR2554
Time frame: 2 years
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