This investigator-initiated, single-center, single-arm, open-label Phase II study will evaluate the efficacy and safety of sonrotoclax in combination with glofitamab, gemcitabine, and oxaliplatin in adults with relapsed or refractory large B-cell lymphoma. Participants will receive six 21-day cycles of glofitamab, gemcitabine, oxaliplatin, and sonrotoclax, followed by six 21-day cycles of glofitamab and sonrotoclax. The primary objective is to evaluate the complete response rate at the end of Cycle 6 according to the Lugano 2014 criteria. The study plans to enroll 39 participants.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
39
Sonrotoclax will be administered orally. In Cycle 1, participants will receive 80 mg on Day 3, 160 mg on Day 4, and 320 mg once daily on Days 5-9. During Cycles 2-12, sonrotoclax will be administered at 320 mg once daily on Days 1-5 of each 21-day cycle.
Glofitamab will be administered intravenously using step-up dosing: 2.5 mg on Cycle 1 Day 8, 10 mg on Cycle 1 Day 15, and 30 mg on Day 1 of Cycles 2-12.
Gemcitabine 1000 mg/m² will be administered intravenously on Cycle 1 Day 2 and on Day 1 of Cycles 2-6.
Oxaliplatin 100 mg/m² will be administered intravenously on Cycle 1 Day 2 and on Day 1 of Cycles 2-6.
Obinutuzumab 1000 mg will be administered intravenously once on Cycle 1 Day 1 as pretreatment before glofitamab administration to reduce the risk of cytokine release syndrome.
The First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, China
Complete Response Rate (CRR) at the End of Induction Treatment
The percentage of participants who achieve a complete response (CR) according to the Lugano 2014 criteria at the end of Cycle 6. Participants who discontinue treatment early because of disease progression or death will be considered non-responders.
Time frame: At the end of Cycle 6 (approximately Week 18)
Objective Response Rate (ORR)
The percentage of participants whose best overall response is complete response (CR) or partial response (PR) according to the Lugano 2014 criteria.
Time frame: From the first dose of study treatment through completion of study treatment, up to approximately 44 weeks
Progression-Free Survival (PFS)
Progression-free survival is defined as the time from the first dose of study treatment to the first documented disease progression or death from any cause, whichever occurs first. Participants without disease progression or death will be censored at the date of the last valid tumor assessment.
Time frame: From the first dose of study treatment until disease progression or death from any cause, up to 48 months
Overall Survival (OS)
Overall survival is defined as the time from the first dose of study treatment to death from any cause. Participants who are alive will be censored at the date they were last known to be alive.
Time frame: From the first dose of study treatment until death from any cause, up to 48 months
Duration of Response (DOR)
Among participants who achieve a complete response (CR) or partial response (PR), duration of response is defined as the time from the first documented response to the first documented disease progression or death from any cause, whichever occurs first.
Time frame: From the first documented CR or PR until disease progression or death from any cause, up to 48 months
Duration of Complete Response (DoCR)
Response (DoCR)Among participants who achieve a complete response (CR), duration of complete response is defined as the time from the first documented CR to the first documented disease progression or death from any cause, whichever occurs first.
Time frame: From the first documented CR until disease progression or death from any cause, up to 48 months
Incidence and Severity of Adverse Events
of Adverse EventsThe incidence, type, and severity of adverse events (AEs), serious adverse events (SAEs), treatment-related adverse events, adverse events leading to treatment interruption, dose reduction or discontinuation, and treatment-related deaths will be assessed. Adverse events will be graded according to NCI CTCAE Version 6.0. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) will be graded according to ASTCT criteria.
Time frame: From informed consent through 28 ± 7 days after the last dose of study treatment; selected toxicities will be followed until resolution or stabilization
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