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

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

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)

Study Overview

• Status: Completed
• Conditions: Relapsed Diffuse Large B-cell Lymphoma; Refractory Diffuse Large B-cell Lymphoma
• Intervention / Treatment: Drug: Ociperlimab; Drug: Tislelizumab; Drug: Rituximab

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing Municipality, China, 100730
      • Beijing Hospital
    • Beijing, Beijing Municipality, China, 100050
      • Beijing Friendship Hospital, Capital Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial Peoples Hospital
    • Guangzhou, Guangdong, China, 510000
      • Zhujiang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat Sen University Cancer Center
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University Branch Donghu
    • Nanchang, Jiangxi, China, 330029
      • Jiangxi Province Cancer Hospital
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Shengjing Hospital of China Medical University
  • Shandong
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Affiliated Zhongshan Hospital of Fudan University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
    • Chengdu, Sichuan, China, 610071
      • Sichuan Academy of Medical Sciences and Sichuan Provincial Peoples Hospital
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310016
      • Sir Run Run Shaw Hospital, Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ociperlimab + Tislelizumab; Participants received ociperlimab 900 mg and tislelizumab 200 mg every three weeks (Q3W) by intravenous injection (IV) until confirmed progressive disease, death, withdrawal of consent, loss of follow-up, or the end of study.	Drug: Ociperlimab; administered intravenously; Other Names: BGB-A1217; Drug: Tislelizumab; Administered intravenously once every 3 weeks; Other Names: BGB-A317; Tevimbra
Experimental: Ociperlimab + Rituximab; Participants received ociperlimab 900 mg and rituximab 375 mg/m² Q3W by intravenous injection until confirmed progressive disease, death, withdrawal of consent, loss of follow-up, or the end of study.	Drug: Ociperlimab; administered intravenously; Other Names: BGB-A1217; Drug: Rituximab; Administered intravenously once every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study drug(s), whether considered related to study drug(s) or not. An SAE is any untoward medical occurrence that, at any dose: Resulted in death; Was life-threatening; Required hospitalization or prolongation of existing hospitalization; Resulted in disability/incapacity; Was a congenital anomaly/birth defect; Was considered a significant medical AE by the investigator based on medical judgement (eg, may jeopardize the patient or may require medical/surgical intervention to prevent one of the outcomes listed above).	From first dose of study drug up to 30 days after last dose, maximum time on treatment was 98 weeks.
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%	21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR is defined as the percentage of participants who achieved a best overall response of partial response (PR) or complete response (CR) based on the Lugano classification as assessed by the investigator. Response was evaluated using computed tomography (CT) and metabolic imaging (fluorodeoxyglucose-positron emission tomography (FDGPET). CR: complete metabolic (no/minimal FDG uptake and no evidence of FDG-avid disease in bone marrow) and radiologic response (target lesions regressed to ≤ 1.5 cm in longest diameter with no extra-lymphatic sites of disease, no organ enlargement and normal bone marrow morphology), no new lesions, and no bone marrow involvement confirmed by bone marrow biopsies (if bone marrow was involved at baseline). PR is partial metabolic (reduced FDG uptake from Baseline) and radiologic response (≥ 50% decrease in size of measurable nodes and extranodal sites, no increase in lesions, and spleen regressed by > 50% in length beyond normal) and no new lesions.	From first dose of study drug to the data cutoff date of 30 August 2024; maximum time on study was 28 months.
Complete Response Rate (CRR)	CRR is defined as the percentage of participants who achieved a complete response per the Lugano Classification (2014) as assessed by the investigator.	From first dose of study drug to the data cutoff date of 30 August 2024; maximum time on study was 28 months.
Duration of Response (DOR)	DOR is defined as the time from the date that response criteria were first met to the date that progressive disease is objectively documented per Lugano Classification (2014), as assessed by the investigator, or death, whichever occurred first. Median DOR was estimated using the Kaplan-Meier method.	Up to the data cutoff date of 30 August 2024; maximum time on study was 28 months.
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	From first dose of study drug to the data cutoff date of 30 August 2024; maximum time on study was 28 months.
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. Median PFS was estimated using the Kaplan-Meier method.	From first dose of study drug to the data cutoff date of 30 August 2024; maximum time on study was 28 months.
Overall Survival (OS)	OS is defined as the time from first study drug administration to the date of death due to any cause. Median OS was estimated using the Kaplan-Meier method.	From first dose of study drug to the data cutoff date of 30 August 2024; maximum time on study was 28 months.
Serum Concentration of Ociperlimab		Predose and end of infusion (EOI) on Cycle 1 Day 1 (C1D1), Cycle 2 Day 1, Cycle 5 Day 1, Cycle 9 Day 1, and Cycle 17 Day 1
Host Immunogenicity: Number of Participants With Anti-drug Antibodies (ADA) to Ociperlimab	The number of participants with anti-drug antibodies to ociperlimab includes participants that were ADA-negative at Baseline and ADA-positive after drug administration during the treatment or follow-up observation period and participants who were positive at Baseline for ADA and with significant increases (4-fold or higher) in ADA titer after drug administration during the treatment or follow-up observation period.	From first dose of study treatment to 30 days after last dose; maximum time on treatment was 98 weeks

Collaborators and Investigators

• Sponsor: BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2022
• Primary Completion (Actual): August 30, 2024
• Study Completion (Actual): August 30, 2024

Study Registration Dates

• First Submitted: February 10, 2022
• First Submitted That Met QC Criteria: February 23, 2022
• First Posted (Actual): March 4, 2022

Study Record Updates

• Last Update Posted (Estimated): September 15, 2025
• Last Update Submitted That Met QC Criteria: August 26, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Lymphoma; Tumor; Large B-cell Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Hemic and Lymphatic Diseases; Neoplasms; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Rituximab; tislelizumab
• Other Study ID Numbers: AdvanTIG-101; CTR20220360 (Other Identifier: ChinaDrugTrials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No