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

Phase 1

Completed

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

Interventions: Drug: Ociperlimab
Drug: Tislelizumab
Drug: Rituximab

Registration Number: NCT05267054

Lead Sponsor: BeiGene

Brief Summary: 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)

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 53

Inclusion Criteria

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.
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.
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.
Ineligible for high dose therapy/hematopoietic stem cell transplantation
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:
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.
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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ociperlimab + Tislelizumab	Ociperlimab	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.
Ociperlimab + Tislelizumab	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.
Ociperlimab + Rituximab	Ociperlimab	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.
Ociperlimab + Rituximab	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	From first dose of study drug up to 30 days after last dose, maximum time on treatment was 98 weeks.	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).
Recommended Phase 2 Dose (RP2D) of Ociperlimab When Administered in Combination With Tislelizumab or Rituximab	21 days	The highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 33.3%

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	From first dose of study drug to the data cutoff date of 30 August 2024; maximum time on study was 28 months.	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.
Complete Response Rate (CRR)	From first dose of study drug to the data cutoff date of 30 August 2024; maximum time on study was 28 months.	CRR is defined as the percentage of participants who achieved a complete response per the Lugano Classification (2014) as assessed by the investigator.
Duration of Response (DOR)	Up to the data cutoff date of 30 August 2024; maximum time on study was 28 months.	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.
Time to Response (TTR)	From first dose of study drug to the data cutoff date of 30 August 2024; maximum time on study was 28 months.	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
Progression-free Survival (PFS)	From first dose of study drug to the data cutoff date of 30 August 2024; maximum time on study was 28 months.	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.
Overall Survival (OS)	From first dose of study drug to the data cutoff date of 30 August 2024; maximum time on study was 28 months.	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.
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	From first dose of study treatment to 30 days after last dose; maximum time on treatment was 98 weeks	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.

Trial Locations

Locations (19): Beijing Friendship Hospital, Capital Medical University
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Beijing, Beijing Municipality, China
Beijing Cancer Hospital
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Beijing, Beijing Municipality, China
Beijing Hospital
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Beijing, Beijing Municipality, China
Zhujiang Hospital of Southern Medical University
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Guangzhou, Guangdong, China
Sun Yat Sen University Cancer Center
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Guangzhou, Guangdong, China
Guangdong Provincial Peoples Hospital
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Guangzhou, Guangdong, China
Henan Cancer Hospital
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Zhengzhou, Henan, China
Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
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Wuhan, Hubei, China
Hunan Cancer Hospital
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Changsha, Hunan, China
The First Affiliated Hospital of Nanchang University Branch Donghu
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Nanchang, Jiangxi, China
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Beijing Friendship Hospital, Capital Medical University
🇨🇳Beijing, Beijing Municipality, China