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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 53
- 试验地点
- 19
- 主要终点
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
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)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •Cohort 1: participants must have positive tumor programmed cell death ligand-1 (PD-L1) immunohistochemistry (IHC) testing results as determined by local pathologist
- •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
- •Relapsed or refractory disease before study entry, defined as either:
- •Recurrent disease after having achieved disease remission (complete response or partial response) during or at the completion of the latest treatment regimen.
- •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
排除标准
- •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-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:
- •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
研究组 & 干预措施
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.
干预措施: Ociperlimab (Drug)
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.
干预措施: Tislelizumab (Drug)
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.
干预措施: Ociperlimab (Drug)
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.
干预措施: Rituximab (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: 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
时间窗: 21 days
The highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 33.3%
次要结局
- 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.)
- 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.)
- Duration of Response (DOR)(Up to the data cutoff date of 30 August 2024; maximum time on study was 28 months.)
- 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.)
- 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.)
- 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.)
- 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)