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

NCT07774234 | Not Yet Recruiting Phase 2

• 1 other identifier: 2026964
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Large B-Cell Lymphoma (LBCL); High-grade B-cell Lymphoma

Keywords

Relapsed Large B-Cell Lymphoma; Refractory Large B-Cell Lymphoma; Diffuse Large B-Cell Lymphoma; Transformed Large B-Cell Lymphoma; EBV-Positive Large B-Cell Lymphoma; High-Grade B-Cell Lymphoma; Double-Hit Lymphoma; Triple-Hit Lymphoma; BCL-2; Sonrotoclax; Glofitamab

Outcome Measures

Primary Outcomes (1)

• 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.

  At the end of Cycle 6 (approximately Week 18)

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  From the first dose of study treatment through completion of study treatment, up to approximately 44 weeks

• Progression-Free Survival (PFS)

  From the first dose of study treatment until disease progression or death from any cause, up to 48 months

• Overall Survival (OS)

  From the first dose of study treatment until death from any cause, up to 48 months

• Duration of Response (DOR)

  From the first documented CR or PR until disease progression or death from any cause, up to 48 months

• Duration of Complete Response (DoCR)

  From the first documented CR until disease progression or death from any cause, up to 48 months

Study Arms (1)

Sonrotoclax + Glofitamab + GemOx

EXPERIMENTAL

Participants will receive 12 treatment cycles, each lasting 21 days. During Cycles 1-6, participants will receive sonrotoclax, glofitamab, gemcitabine, and oxaliplatin. During Cycles 7-12, participants will receive sonrotoclax and glofitamab. Obinutuzumab will be administered once on Cycle 1 Day 1 as pretreatment before glofitamab step-up dosing.

Drug: Sonrotoclax; Biological: Glofitamab; Drug: Gemcitabine (1000 mg/m2); Drug: Oxaliplatin; Biological: Obinutuzumab

Interventions

Sonrotoclax DRUG

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.

Sonrotoclax + Glofitamab + GemOx

Glofitamab BIOLOGICAL

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.

Sonrotoclax + Glofitamab + GemOx

Gemcitabine (1000 mg/m2) DRUG

Gemcitabine 1000 mg/m² will be administered intravenously on Cycle 1 Day 2 and on Day 1 of Cycles 2-6.

Sonrotoclax + Glofitamab + GemOx

Oxaliplatin DRUG

Oxaliplatin 100 mg/m² will be administered intravenously on Cycle 1 Day 2 and on Day 1 of Cycles 2-6.

Sonrotoclax + Glofitamab + GemOx

Obinutuzumab BIOLOGICAL

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.

Sonrotoclax + Glofitamab + GemOx

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• 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.
• 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.
• 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.
• Estimated life expectancy greater than 3 months.
• Ability and willingness to provide written informed consent and comply with the study protocol.

You may not qualify if:

• 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.
• 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.
• Severe hypersensitivity to glofitamab, obinutuzumab, gemcitabine, oxaliplatin, sonrotoclax, or any of their excipients.
• Active infection that, in the investigator's judgment, cannot be adequately controlled.
• Human immunodeficiency virus (HIV) infection or inadequately controlled active hepatitis B virus or hepatitis C virus infection.
• High and inadequately controlled risk of tumor lysis syndrome before enrollment.
• 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.
• Current malignancy or another malignancy diagnosed within 3 years before enrollment, except for cured low-risk malignancies.
• 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.
• Active bleeding, coagulation disorder, or an unacceptable bleeding risk as determined by the investigator.
• Pregnancy or breastfeeding, or plans to become pregnant or father a child during the study period.
• 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.

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

glofitamab; Gemcitabine; Oxaliplatin; obinutuzumab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Study Officials

• Ting Xu

  The First Affiliated Hospital of Soochow University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ting Xu

CONTACT

+86 151 6247 6547; xt21132075@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2026
• First Posted: August 19, 2026
• Study Start: August 20, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): August 20, 2030
• Last Updated: August 19, 2026

Record last verified: 2026-08

Locations

CN (1)