Treatment of Relapsed or Refractory Diffuse Large B Cell Lymphoma With Ociperlimab (BGB A1217) in Combination With Tislelizumab (BGB A317) or Rituximab

Study Overview
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Brief Summary
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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)

Official Title
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A Phase 1b/2 Study Investigating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Ociperlimab (BGB A1217) in Combination With Tislelizumab (BGB A317) or Rituximab in Patients With Relapsed or Refractory Diffuse Large B Cell Lymphoma

Conditions
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Relapsed Diffuse Large B-cell Lymphoma, Refractory Diffuse Large B-cell Lymphoma

Intervention / Treatment
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* Drug: Ociperlimab
* Drug: Tislelizumab
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Histologically confirmed DLBCL NOS (Not Otherwise Specified), 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 a. Cohort 1: participants must have positive tumor PD L1 IHC testing results as determined by local pathologist b. Cohort 2: participants must have negative tumor PD L1 IHC testing results as determined by local pathologist 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: a. Recurrent disease after having achieved disease remission (CR or PR) during or at the completion of the latest treatment regimen b. Stable disease or 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: Current or history of central nervous system lymphoma Histologically transformed lymphoma Receipt of the following treatment: 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 Recent treatment with another monoclonal antibody within 4 weeks before first dose of study drug Investigational treatment within 4 weeks (or 5 half lives, whichever is shorter) before first dose of study drug Treatment with autologous stem cell transplantation within 6 months before first dose of study drug Treatment with allogeneic hematopoietic stem cell transplantation or organ transplantation Treatment with anti PD-1, anti PD-L1, anti PD-L2, anti TIGIT, anti CTLA4 or other antibody or drug specifically targeting T cell costimulation or checkpoint pathways Active autoimmune diseases or history of autoimmune diseases that may relapse, with the following exceptions: Controlled Type 1 diabetes Hypothyroidism (provided that it is managed with hormone replacement therapy only) Controlled celiac disease Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, or alopecia) 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 (participants with PD-L1 positive on the surface of tumor cells)<br>participants will receive ociperlimab in combination with tislelizumab | Drug: Ociperlimab<br>* administered intravenously<br>* Other names: BGB-A1217;Drug: Tislelizumab<br>* administered intravenously<br>* Other names: BGB A317;|
| Experimental: Cohort 2 (participants with PD-L1 negative on the surface of tumor cells<br>participants will receive ociperlimab in combination with rituximab | Drug: Ociperlimab<br>* administered intravenously<br>* Other names: BGB-A1217;Drug: Rituximab<br>* administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs) | Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) | Up to 2.5 years | 
| Recommended Phase 2 dose (RP2D) of ociperlimab when administered in combination with tislelizumab or rituximab | The highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 33.3% | Up to 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR is defined as the percentage of participants with partial or complete response, as assessed by the investigator using the Lugano Classification (2014) | Up to 2.5 years | 
| Complete response rate (CRR) | CRR is defined as the percentage of participants who achieve a complete response per RECIST v1.1 Lugano Classification (2014) as assessed by the investigator | Up to 2.5 years | 
| Duration of response (DOR) | DOR is defined as the time from the date that response criteria are first met to the date that progressive disease is objectively documented per Lugano Classification (2014), as assessed by the investigator, or death, whichever comes first | Up to 2.5 years | 
| Time to response (TTR) | TTR is defined as the time from study treatment start to date of the earliest qualifying response (partial response or better) per Lugano Classification (2014) as assessed by the investigator | Up to 2.5 years | 
| Progression-free survival (PFS) | PFS is defined as the time from first dose until first documentation of progression per Lugano Classification (2014), as assessed by the investigator, or death, whichever comes first | Up to 2.5 years | 
| Overall survival (OS) | OS is defined as the time from first study drug administration to the date of death due to any cause | Up to 2.5 years | 
| Serum concentration of ociperlimab in combination with tislelizumab or rituximab |  | Up to 2.5 years | 
| Host Immunogenicity: incidence of anti-drug antibodies (ADA) of ociperlimab (in combination with tislelizumab or rituximab) |  | Up to 2.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, Tumor, Large B-cell Lymphoma