The goal of this clinical trial is to learn if drug GSK5926371 works to treat a form of B-cell cancer (a type of blood cancer) that has returned or failed to respond to prior therapies in adults. The study will primarily assess the drugs safety and tolerability in participants. Additionally, it seeks to determine the clinical efficacy and pharmacokinetic (PK) properties of GSK5926371.

Inclusion Criteria:

• Has histologically confirmed Relapsed/Refractory (R/R) B-NHL, for which systemic treatment is indicated,

  1. Has measurable disease,
  2. Has received at least 2 prior lines of systemic anti-neoplastic therapy, including an anti-CD20-containing combination appropriate for the indication;
  3. Has documented disease relapse, progression or disease refractory to the most recent line of therapy, per Lugano criteria.:

• Willing to use adequate contraception (Participant of childbearing potential [POCBP] only).

• Is capable of giving signed informed consent

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

• Has adequate organ function.

Exclusion Criteria:

• Has a malignancy (except disease under study) that has progressed or required active treatment within the past 24 months except for basal cell or squamous cell carcinomas of the skin or in-situ carcinomas (e.g., breast, cervix, bladder) that have been resected with no evidence of metastatic disease.
• Has had any major surgery within 4 weeks prior to the first dose of GSK5926371 or has not recovered from prior surgeries or complications.
• Has a history of Progressive multifocal leukoencephalopathy (PML), current central nervous system (CNS) involvement by lymphoma, or a history of significant CNS disease such as uncontrolled seizures, stroke, epilepsy, CNS vasculitis, and neurodegenerative conditions.
• Has an active uncontrolled infection.
• Has received a prior Allogeneic stem cell transplant (allo-SCT) within 12 months prior to the first dose of GSK5926371 or has active graft-versus-host disease requiring systemic immunosuppressive therapy.
• Has received a prior autologous stem cell transplant within 100 days prior to the first dose of GSK5926371.
• Has received prior treatment with Chimeric antigen receptor T-cell (CAR-T) therapy within 12 weeks of first GSK5926371 administration.
• Has received prior treatment with CD19- or CD20-targeting Bispecific antibody (BsAbs) within 8 weeks of the first dose of study intervention.
• Has QT interval corrected (QTc) >450 milliseconds (msec) or QTc >480 msec for participants with bundle branch block.
• Has significant cardiovascular disease such as uncontrolled arrhythmias, Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification, ejection fraction <=45% by any methods in the 12 months of enrollment, unstable angina or acute coronary syndrome including myocardial infarction within 6 months of enrollment.

Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/gsk-patient-level-data-sharing-july2025.pdf