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.