The primary purpose of this study is to assess the safety and tolerability of ociperlimab (BGB-A1217) in combination with tislelizumab (BGB-A317) or rituximab in participants with relapsed or refractory (R/R) diffuse large B cell lymphoma (DLBCL)

Inclusion Criteria:

1. Histologically confirmed DLBCL NOS (Not Otherwise Specified), Epstein-Barr virus (EBV) + DLBCL NOS, or high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (double/triple-hit lymphoma [DHL/THL]), based on the World Health Organization (WHO) 2016 classification of tumors of hematopoietic and lymphoid tissue

   1. Cohort 1: participants must have positive tumor programmed cell death ligand-1 (PD-L1) immunohistochemistry (IHC) testing results as determined by local pathologist
   2. Cohort 2: Participants must have negative tumor PD-L1 IHC results as determined by a local pathologist in the dose confirmation stage. The dose expansion stage can enroll participants regardless of PD-L1 expression.

2. Previously received ≥ 1 line of adequate systemic anti DLBCL therapy, defined as an anti CD20 antibody based chemoimmunotherapy for ≥ 2 consecutive cycles, unless participants had PD before Cycle 2.

3. Relapsed or refractory disease before study entry, defined as either:

   1. Recurrent disease after having achieved disease remission (complete response or partial response) during or at the completion of the latest treatment regimen.
   2. Stable disease or progressive disease (PD) at the completion of the latest treatment regimen.

4. Ineligible for high dose therapy/hematopoietic stem cell transplantation

5. Measurable disease as assessed by computed tomography (CT) or magnetic resonance imaging (MRI) and defined as at least 1 lymph node > 1.5 cm in the longest diameter and/or at least 1 extranodal lesion > 1.0 cm in the longest diameter, and measurable lesion (s) in 2 perpendicular diameters

Exclusion Criteria:

1. Current or history of central nervous system lymphoma

2. Histologically transformed lymphoma

3. Receipt of the following treatment:

   1. Systemic chemotherapy, targeted small molecule therapy or radiation therapy within 4 weeks (or 5 half lives, whichever is shorter) before first dose of study drug
   2. Recent treatment with another monoclonal antibody within 4 weeks before first dose of study drug
   3. Investigational treatment within 4 weeks (or 5 half lives, whichever is shorter) before first dose of study drug
   4. Treatment with autologous stem cell transplantation within 6 months before first dose of study drug
   5. Treatment with allogeneic hematopoietic stem cell transplantation or organ transplantation
   6. Treatment with anti-programmed cell death protein-1 (PD-1), anti PD-L1, anti PD-L2, anti T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT), anti CTLA4 or other antibody or drug specifically targeting T cell costimulation or checkpoint pathways.

4. Active autoimmune diseases or history of autoimmune diseases that may relapse, with the following exceptions:

   1. Controlled Type 1 diabetes
   2. Hypothyroidism (provided that it is managed with hormone replacement therapy only)
   3. Controlled celiac disease
   4. Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, or alopecia)
   5. Any other disease that is not expected to recur in the absence of external triggering factors

Note: Other protocol defined Inclusion/Exclusion criteria may apply

BeiGene shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeiGene shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeiGene review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

See plan description

See plan description