This is a Phase I/II study. The Phase I part will evaluate the safety and tolerability of sonrotoclax in combination with polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP), using a standard 3+3 dose-escalation design, to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D). The Phase II part will assess the efficacy of the combination regimen in patients with previously untreated LBCL with high BCL2 expression or MYC/BCL2 rearrangements.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Polatuzumab vedotin IV infusion will be administered as per the schedule specified in the respective arm
Rituximab IV infusion will be administered as per the schedule specified in the respective arm.
Cyclophosphamide IV infusion will be administered as per the schedule specified in the respective arm.
Ruijin Hospital, Shanghai JiaoTong University School of Medicine
Shanghai, Shanghai Municipality, China
Maximum tolerated dose (MTD) of sonrotoclax in combination with Pola-R-CHP
The MTD is defined as the highest dose at which the incidence of dose-limiting toxicity (DLT) is less than 1/3 of patients.
Time frame: From first dose through 21 consecutive calendar days after reaching the target dose (up to 26 days)
Recommended Phase II Dose (RP2D)
The determined Maximum Tolerated Dose (MTD) and its dosing regimen will serve as the recommended Phase II dose (RP2D) for the combination regimen, unless safety data support the use of a lower dose.
Time frame: At completion of the DLT evaluation period, up to 26 days
Complete response rate
CR rate at the end of treatment by FDG-PET defined as the proportion of participants with CR at the end of treatment according to the 2014 Lugano Response Criteria; as determined by the investigator and IRC (separately)
Time frame: End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]
Objective response rate
ORR at treatment completion or discontinuation defined as the proportion of participants with CR or partial response (PR) at the end of treatment according to the 2014 Lugano Response Criteria; as determined by the investigator and IRC(separately)
Time frame: End of treatment visit (6-8 weeks after last dose on Day 1 of Cycle 6 [Cycle length=21 days]
Progression-free survival
PFS, defined as the time from diagnosis to the first occurrence of disease progression or relapse using the 2014 Lugano Response Criteria or death due to any cause, whichever occurs first; as determined by the investigator
Time frame: From enrollment to the first occurrence of disease progression or relapse, or death from any cause, whichever occurs earlier (up to 24 months)
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Doxorubicin IV infusion will be administered as per the schedule specified in the respective arm.
Prednisone PO will be administered as per the schedule specified in the respective arm.
Sonrotoclax PO will be administered as per the schedule specified in the respective arm.
Overall survival
OS defined as the time from diagnosis to death from any cause
Time frame: up to approximately 3 years
Duration of Response
The time from the first documentation of a complete response (CR) or partial response (PR) to the first documentation of disease progression (PD), death from any cause, or the last follow-up, whichever occurs first.
Time frame: From enrollment to the first occurrence of disease progression or relapse, or death from any cause, whichever occurs earlier (up to 24 months)
Safety and Tolerability
Determined by monitoring the occurrence, severity, and management of adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs).The severity of adverse events is graded (Grade 1-5) using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE); Tolerability is determined by whether patients can tolerate the dosage and treatment cycle of the study regimen, and whether dose adjustment, treatment interruption, or withdrawal from the trial is required due to adverse events.
Time frame: From enrollment to study completion, a maximum of 3 years