Sonrotoclax, Glofitamab, Gemcitabine, and Oxaliplatin for Relapsed or Refractory Large B-Cell Lymphoma

Inclusion Criteria:

1. 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.
2. 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.
3. Age 18 years or older.
4. 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.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
6. Adequate organ function, including left ventricular ejection fraction (LVEF) of at least 50%; creatinine clearance of at least 50 mL/min, although a minimum of 40 mL/min may be acceptable if the investigator determines that treatment can be administered safely; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) no greater than 3 × the upper limit of normal (ULN), or no greater than 5 × ULN in the presence of hepatic involvement; total bilirubin no greater than 1.5 × ULN, or no greater than 3 × ULN in participants with Gilbert syndrome or hepatobiliary involvement; and corrected electrolytes and tumor lysis syndrome-related laboratory parameters considered suitable for treatment.
7. Adequate hematologic function, including absolute neutrophil count (ANC) of at least 1.0 × 10\^9/L, platelet count of at least 50 × 10\^9/L, and hemoglobin of at least 60 g/L. Transfusion support to meet these criteria is permitted. Participants with cytopenias attributable to bone marrow involvement by lymphoma are exempt from these hematologic requirements.
8. A negative pregnancy test for women of childbearing potential. Male and female participants must agree to use effective contraception during study treatment and for the protocol-specified period after the last dose of study treatment.
9. Estimated life expectancy greater than 3 months.
10. Ability and willingness to provide written informed consent and comply with the study protocol.

Exclusion Criteria:

1. Previous central nervous system involvement by lymphoma, including involvement of the brain parenchyma, meninges, cerebrospinal fluid, spinal cord, or intraocular structures.
2. Major surgery or serious trauma within 2 weeks before enrollment, or clinically significant treatment-related adverse effects that have not adequately recovered.
3. History of cerebral infarction or intracranial hemorrhage within 3 months before enrollment.
4. Prior treatment with glofitamab.
5. Documented disease progression during or after prior treatment with a BCL-2 inhibitor when, in the investigator's judgment, the participant is unlikely to derive benefit from sonrotoclax.
6. Severe hypersensitivity to glofitamab, obinutuzumab, gemcitabine, oxaliplatin, sonrotoclax, or any of their excipients.
7. Active infection that, in the investigator's judgment, cannot be adequately controlled.
8. Human immunodeficiency virus (HIV) infection or inadequately controlled active hepatitis B virus or hepatitis C virus infection.
9. Failure to meet the required washout period from prior antitumor therapy, including chemotherapy, radiotherapy, or antibody-drug conjugate therapy within 2 weeks or within 5 half-lives; monoclonal antibody or bispecific antibody therapy within 4 weeks; CAR T-cell therapy within 30 days; or autologous stem cell transplantation within 3 months. Prior allogeneic stem cell transplantation or active graft-versus-host disease is also exclusionary.
10. High and inadequately controlled risk of tumor lysis syndrome before enrollment.
11. Severe cardiovascular or pulmonary disease, including New York Heart Association Class III-IV heart failure, myocardial infarction within 6 months, unstable arrhythmia or angina, severe chronic obstructive pulmonary disease, active pneumonia, requirement for long-term supplemental oxygen, or resting oxygen saturation of 90% or lower.
12. Current malignancy or another malignancy diagnosed within 3 years before enrollment, except for cured low-risk malignancies.
13. Use of systemic corticosteroids equivalent to prednisone greater than 20 mg/day within 2 weeks before enrollment when the dose cannot be reduced to an acceptable level.
14. Active bleeding, coagulation disorder, or an unacceptable bleeding risk as determined by the investigator.
15. Pregnancy or breastfeeding, or plans to become pregnant or father a child during the study period.
16. Psychiatric illness, cognitive impairment, drug or alcohol dependence, or any other factor that may interfere with understanding the study, providing informed consent, or complying with study procedures and follow-up.
17. Any other condition that, in the investigator's judgment, may compromise participant safety, interfere with study conduct, or confound interpretation of study data.