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.
Histologically confirmed CD20-positive relapsed or refractory large B-cell lymphoma, including diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS); large B-cell lymphoma transformed from an indolent B-cell lymphoma; EBV-positive large B-cell lymphoma; high-grade B-cell lymphoma; and double-hit or triple-hit lymphoma with MYC and BCL2 and/or BCL6 rearrangements.
At least one prior line of systemic anti-lymphoma therapy. Prior treatment should generally have included an anti-CD20 monoclonal antibody and an anthracycline, unless there was a clear contraindication or the treatment was unavailable.
Age 18 years or older.
At least one evaluable or measurable target lesion, defined as a lymph node lesion with a longest diameter greater than 1.5 cm or an extranodal lesion with a longest diameter greater than 1.0 cm.
Previous central nervous system involvement by lymphoma, including involvement of the brain parenchyma, meninges, cerebrospinal fluid, spinal cord, or intraocular structures.
Major surgery or serious trauma within 2 weeks before enrollment, or clinically significant treatment-related adverse effects that have not adequately recovered.
History of cerebral infarction or intracranial hemorrhage within 3 months before enrollment.
Prior treatment with glofitamab.
Single group
Sonrotoclax
DrugSonrotoclax 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
Biological/VaccineGlofitamab 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)
DrugGemcitabine 1000 mg/m² will be administered intravenously on Cycle 1 Day 2 and on Day 1 of Cycles 2-6.
Oxaliplatin
DrugOxaliplatin 100 mg/m² will be administered intravenously on Cycle 1 Day 2 and on Day 1 of Cycles 2-6.
Obinutuzumab
Biological/VaccineObinutuzumab 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.
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.
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.
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.
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.
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.
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