A Phase 1/2 Open-label, Multicenter Study Evaluating the Safety and Pharmacokinetics of Imvotamab (IGM-2323) as a Single Agent and in Combination in Subjects With Relapsed/Refractory Non-Hodgkin Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 97
- 试验地点
- 26
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
This is a Phase 1/2 study of imvotamab in adult subjects with relapsed or refractory B-cell Non-Hodgkin Lymphoma. This study will consist of a dose-escalation stage, a combination stage, and a randomized dose-expansion stage where subjects will be enrolled into indication-specific expansion cohorts. imvotamab will be administered intravenously (IV).
Additional CD20-positive NHL histologies (e.g. MZL and MCL), may be allowed with Medical Monitor approval during the Dose-Escalation Phase of the study.
详细描述
Imvotamab is an engineered bispecific IgM antibody for the treatment of patients with CD20-positive cancers. It contains ten high affinity binding domains for CD20, and one binding domain for CD3. Imvotamab is able to eliminate CD20-positive lymphoma cells by engaging T-cells and lymphoma cells, leading to T-cell dependent cellular cytotoxicity. Additionally, imvotamab is also able to eliminate lymphoma cells by recruiting complement to the surface of lymphoma cells, leading to complement dependent cytotoxicity.
In our preclinical studies, we observed activity against rituximab resistant cells carrying low levels of CD20. We have also observed much lower cytokine release with imvotamab relative to comparable IgG format bispecific T-cell engaging antibodies, which is expected to result in reduced risk of the serious adverse effects from cytokine release syndrome (CRS).
For the combination stage, imvotamab will be combined with loncastuximab tesirine, a CD19-targeting antibody drug conjugate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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
- •> 18 years of age: ECOG PS 0 or 1
- •Relapsed or Refractory Follicular Lymphoma (FL), and Diffuse Large B-cell Lymphoma (DLBCL), Mantle cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL) in dose escalation
- •Relapsed or refractory to at least two prior systemic treatment regimens (must include anti-CD20 chemo-immunotherapy regimen). FL/MZL may be enrolled with a least 2 prior systemic regimens which must include an anti-CD20, without the need for a prior chemotherapy regimen)
- •At least one bi-dimensionally measurable lesion (>1.5cm in it's longest dimension by computerized tomography (CT scan)
- •Good organ function
- •Not eligible for autologous stem cell transplant (DLBCL subjects), due to chemoresistant disease, medically unfit (organ function), or unwilling.
排除标准
- •Prior allogeneic transplant
- •ASCT within 100 days prior to the first imvotamab administration.
- •Lack of response to prior treatment with CAR-T therapy, subjects with less than 3 months from prior CAR-T therapy to first dose of imvotamab, and prior CAR-T therapy only allowed with Medical Monitor approval.
- •Concurrent serious co-morbidities that could limit patients full participation and compliance.
- •Prior CD-targeting bispecific antibodies.
- •Prior loncastuximab tesirine.
研究组 & 干预措施
Phase 1a (Dose Escalation)
Subjects will receive imvotamab via intravenous (IV) infusion weekly. No longer enrolling.
干预措施: imvotamab (Drug)
Phase 1a (Q3W)
Subjects will receive imvotamab via intravenous (IV) infusion every 3 weeks. No longer enrolling.
干预措施: imvotamab (Drug)
Phase 1a (Prior bi-specific)
Subjects treated with prior bi-specifics will receive imvotamab via IV infusion weekly. No longer enrolling.
干预措施: imvotamab (Drug)
Phase 2 (DLBCL)
DLBCL subjects will receive imvotamab via IV infusion at a dose and schedule to be determined after reviewing all available response and safety data. No longer enrolling.
干预措施: imvotamab (Drug)
Phase 2 (FL)
FL subjects will receive imvotamab via IV infusion at a dose and schedule to be determined after reviewing all available response and safety data. No longer enrolling.
干预措施: imvotamab (Drug)
Phase 1b (Combination)
Subjects will receive imvotamab via IV infusion weekly and loncastuximab tesirine via IV infusion every 3 weeks.
干预措施: imvotamab (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: Baseline up to 5 years
Percentage of measurable disease in subjects who have achieved either complete response (CR) or partial response (PR)
Overall Frequency of Adverse Events
时间窗: Baseline through approximately 30 days after last study treatment
Percentage of Adverse Events
次要结局
- Duration of Response (DOR)(Baseline up to 5 years)
- Objective Response Rate (ORR)(Baseline up to 5 years)