NCT02290951已完成1 期
An Open-Label, Multi-Center Phase 1 Study to Investigate the Safety and Tolerability of REGN1979, an Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody, in Patients With CD20+ B-Cell Malignancies Previously Treated With CD20-Directed Antibody Therapy (ELM-1)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 200
- 试验地点
- 22
- 主要终点
- Safety/overall frequency of adverse events (AEs)
研究概览
简要总结
This study has two parts with distinct study objectives and study design. In part A, odronextamab is studied as an intravenous (IV) administration with a dose escalation and a dose expansion phase for B-NHL and CLL. The dose escalation phase for B-NHL and the CLL study are closed at the time of protocol amendment 17. In part B, odronextamab is studied as a subcutaneous (SC) administration with a dose finding and a dose expansion phase for B-NHL.
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
- •Have documented CD20+ B-cell malignancy, with active disease not responsive to prior therapy, for whom no standard of care options exists, and for whom treatment with an anti-CD20 antibody may be appropriate:
- •Part A (IV administration) B-NHL confirmed by National Cancer Institute (NCI) working group criteria
- •Part B (SC administration): Confirmed diagnosis of B-NHL requiring therapy as defined by WHO classification 2017
- •Patients with B-NHL must have had prior treatment with an anti-CD20 antibody therapy. Patients with CLL (Part A only) are not required to have received prior treatment with an anti-CD20 antibody therapy as defined in the protocol.
- •For the inclusion in the disease-specific expansion cohort enrolling DLBCL patients after failure of CAR-T therapy, the patient must have recovered from the toxicities of the lymphodepletion therapy and CAR-T infusion.
- •For inclusion in Part B, patients must have FL grade 1-3a or DLBCL (with or without prior CAR-T) per the criteria above, and:
- •Patients with FL grade 1-3a and DLBCL must have received at least 2 prior lines of systemic therapy, including an anti-CD20 antibody and an alkylating agent
- •All patients must have at least one bi-dimensionally measurable lesion ≥1.5 cm) documented by CT or MRI scan, if CT scan is not feasible.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤1
- •Life expectancy of at least 6 months
- •Adequate bone marrow function as described in the protocol
- •Adequate organ function as described in the protocol
- •Willingness to undergo mandatory tumor biopsy pretreatment, if in the opinion of the investigator, the patient has an accessible lesion that can be biopsied without significant risk to the patient.
- •Willing and able to comply with clinic visits and study-related procedures
- •Provide signed informed consent or legally acceptable representative
排除标准
- •Primary central nervous system (CNS) lymphoma or known or suspected CNS involvement by non-primary CNS NHL
- •History of or current relevant CNS pathology such as
- •Epilepsy, seizure, paresis, aphasia, apoplexia, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis, or
- •Evidence for presence of inflammatory lesions and/or vasculitis on cerebral MRI
- •Standard anti-lymphoma chemotherapy (non-biologic) or radiotherapy within 28 days prior to first administration of study drug
- •Infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or cytomegalovirus (CMV) infection [(as noted by detectable levels on a blood polymerase chain reaction (PCR) assay)].
- •Patients with hepatitis B (HepBsAg+) who have controlled infection (serum hepatitis B virus deoxyribonucleic acid (DNA) that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) are permitted upon consultation with the physician managing the infection.
- •Patients who show detectable levels of CMV at screening will need to be treated with appropriate antiviral therapy and demonstrate at least 2 undetectable levels of CMV by PCR assay (at least 7 days apart) before being re-considered for eligibility.
- •Patients who have received a live vaccination within 28 days of first dose of study treatment
- •Note: Other protocol Inclusion/Exclusion criteria apply
研究组 & 干预措施
Part A
Experimental
DLBCL post CAR-T
干预措施: Odronextamab multiple dose levels (Drug)
1N Part B
Experimental
FL
干预措施: Odronextamab multiple dose levels (Drug)
2N Part B
Experimental
DLBCL
干预措施: Odronextamab multiple dose levels (Drug)
结局指标
主要结局
Safety/overall frequency of adverse events (AEs)
时间窗: Up to 24 months
Part A and B
Safety/dose limiting toxicities (DLTs)
时间窗: Up to 28 days
Part A and B
Antitumor activity as measured by the objective response rate (ORR)
时间窗: Through study completion, an average of 24 months
Expansion Cohorts: • Diffuse large B-cell lymphoma (DLBCL) after failure of CAR-T therapy Part A
次要结局
- Pharmacokinetics (Concentration of odronextamab)(Up to 10 months)
- Titer of ADA to odronextamab(Over time; up to approximately 15 months)
- Incidence of neutralizing antibodies (NAb) to odronextamab over time(Over time; Up to approximately 15 months)
- Incidence of anti-drug antibodies (ADA) to odronextamab(Over time; up to approximately 15 months)
- Objective response rate (ORR)(Through study completion, an average of 24 months)
- Progression-free survival(Up to 48 months)
- Overall Survival(Until death or lost to follow-up/ withdrawal, approximately up to 48 months)
- Duration of response (DOR)(Until progression, approximately up to 48 months)
- Minimal residual disease (MRD) for patients with CLL(Up to 24 months)
- Duration of Complete Response (DOCR)(Until progression, approximately up to 48 months)
研究者
研究点 (22)
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相关资讯
Odronextamab Shows Promise in DLBCL After CAR T-Cell Therapy Failure- Odronextamab demonstrates efficacy in diffuse large B-cell lymphoma (DLBCL) patients who have relapsed after CAR T-cell therapy, offering a potential treatment option.
- The ELM-1 study reveals that the duration of benefit from prior CAR T-cell therapy is a key predictor of response to odronextamab.
- Patients relapsing more than 6 months post-CAR T-cell therapy exhibit higher response rates to odronextamab compared to those relapsing sooner.
- Combination approaches with odronextamab are being explored to improve outcomes for DLBCL patients after CAR T-cell therapy failure.last yearOdronextamab Shows Manageable Safety Profile in DLBCL Patients Post-CAR T-cell Therapy- Odronextamab monotherapy demonstrates a manageable safety profile in patients with diffuse large B-cell lymphoma (DLBCL) who have progressed after CAR T-cell therapy.
- The most common adverse event was low-grade cytokine release syndrome (CRS), with primarily grade 1 or 2 events reported and no grade 5 CRS instances observed.
- Infectious complications occurred as expected in this patient population, and the CAR-HEMATOTOX model may help identify patients at higher risk.
- Odronextamab shows promise in treating patients after relapse following CAR T-cell therapy, with durable responses observed in patients achieving complete remission.last year