NCT05169515进行中（未招募）1 期
A Phase Ib, Open-Label, Multicenter Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab or Glofitamab in Combination With CC-220 and/or CC-99282 in Patients With B-Cell Non-Hodgkin Lymphoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 121
- 试验地点
- 39
- 主要终点
- Percentage of participants with dose-limiting toxicities (DLTs) [dose escalation]
研究概览
简要总结
This study will evaluate the safety, efficacy, and pharmacokinetics of mosunetuzumab or glofitamab in combination with CELMoDs (CC-220 and/or CC-99282) in participants with B-cell NHL.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Age >/= 18 years
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
- •History of one of the following histologically documented hematologic malignancies that are expected to express the CD20 antigen: In the Dose Escalation phase, participants must have relapsed after or failed to respond to at least two prior lines of systemic therapy. In the Dose Expansion phase, participants with FL Grades 1-3a must have relapsed after or failed to respond to at least one prior line of systemic therapy and must require systemic therapy. Participants with DLBCL/transformed FL must have relapsed after or failed to respond to at least one prior systemic treatment regimen.
- •Participants with DLBCL/transformed FL who have received only one prior line of therapy must: Not be considered a candidate for autologous stem cell transplantation (ASCT) due to age, performance status, comorbidities and/or insufficient response to prior treatment, or have refused ASCT; or be ineligible for or unable to receive chimeric antigen receptor T-cell (CAR-T) therapy due to reasons defined by the protocol
- •Fluorodeoxyglucose-avid lymphoma (i.e. PET-positive lymphoma)
- •At least one bi-dimensionally measurable nodal lesion (> 1.5 cm in its largest dimension by diagnostic quality CT or PET/CT scan), or at least one bi-dimensionally measurable extranodal lesion (> 1.0 cm in its largest dimension by diagnostic quality CT or PET/CT scan)
- •Availability of a representative tumor specimen and the corresponding pathology report for confirmation of the diagnosis of NHL
- •A fresh pretreatment biopsy during screening period, excisional or incisional, is preferred
- •Adequate hematologic function without growth factors or blood product transfusion within 14 days of first dose of study drug administration
- •Normal laboratory values
- •All participants and health care providers will be trained and counseled on pregnancy prevention. For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception during the treatment period and for 3 months after the final dose of mosunetuzumab, at least 18 months after pre-treatment with obinutuzumab or 2 months after the last dose of glofitamab, 28 days after the last dose of CC-220, 28 days after the last dose of CC-99282, 3 months after the last dose of tocilizumab (if applicable), whichever is longer
- •For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm during the treatment period and for at least 3 months after pre-treatment with obinutuzumab or 2 months after the last dose of glofitamab, 28 days after the last dose of CC-220, 28 days after the last dose of CC- 99282, 2 months after the final dose of tocilizumab (if applicable), whichever is longer
排除标准
- •* Pregnancy or breastfeeding, or intention of becoming pregnant during the study (female participants of childbearing potential must have a negative serum pregancy test result within 14 days prior to initiation of the study treatment) or within 3 months after the final dose of mosunetuzumab, at least 3 months after pre-treatment with obinutuzumab or 2 months after the last dose of glofitamab, whichever is longer, 28 days after the last dose of CC-220, 28 days after the last dose of CC-9282, 3 months after the final dose of tocilizumab, whichever is longer
- •* Participant has received prior therapy with cereblon (CRBN)-modulating drug (e.g., lenalidomide, avadomide/CC-122, pomalidomide) \= Grade 2 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), despite medical management
- •* QTc interval of \> 470 ms
- •* The following treatments prior to study entry: mosunetuzumab, glofitamab, or other CD20/CD3-directed bispecific antibodies; allogenic stem cell therapy (SCT); solid organ transplantation
- •* Treatments (investigational or approved) within the following time periods prior to initiation/first dose of study treatment: radiotherapy within 2 weeks; autologous SCT within 100 days; chimeric antigen receptor (CAR) T-cell therapy within 30 days; prior anti-lymphoma treatment with monoclonal antibodies or antibody-drug conjugates within 4 weeks; use of radioimmunoconjugates within 12 weeks; systemic immunosuppressive medications within 2 weeks; any other anti-cancer therapy, whether investigational or approved, including but not limited to chemotherapy, within 4 weeks or 5 half-lives of the drug, whichever is shorter
- •* Live, attenuated vaccine within 4 weeks before first dose of study treatment, or in whom it is anticipated that such a live attenuated vaccine will be required during the study period or within 5 months after the final dose of study treatment
- •* Current or past history of central nervous system (CNS) lymphoma or leptomeningeal infiltration
- •* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
- •* History of autoimmune disease, including but not limited to myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, granulomatosis with polyangiitis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
- •* Major surgery or significant traumatic injury \< 28 days prior to enrollment (excluding biopsies) or anticipation of the need for major surgery during study treatment
- •* Clinically significant toxicities from prior treatment have not resolved to Grade \
研究组 & 干预措施
Arm 1
Experimental
Participants will receive subcutaneous (SC) mosunetuzumab + CC-220 (dose escalation only) or SC mosunetuzumab + CC-99282.
干预措施: SC Mosunetuzumab (Drug)
Arm 2
Experimental
Participants will receive intravenous (IV) glofitamab + CC-99282.
干预措施: Obinutuzumab (Drug)
Arm 2
Experimental
Participants will receive intravenous (IV) glofitamab + CC-99282.
干预措施: Tocilizumab (Drug)
Arm 2
Experimental
Participants will receive intravenous (IV) glofitamab + CC-99282.
干预措施: Golcadomide (Drug)
Arm 1
Experimental
Participants will receive subcutaneous (SC) mosunetuzumab + CC-220 (dose escalation only) or SC mosunetuzumab + CC-99282.
干预措施: Golcadomide (Drug)
Arm 1
Experimental
Participants will receive subcutaneous (SC) mosunetuzumab + CC-220 (dose escalation only) or SC mosunetuzumab + CC-99282.
干预措施: Tocilizumab (Drug)
Arm 2
Experimental
Participants will receive intravenous (IV) glofitamab + CC-99282.
干预措施: IV Glofitamab (Drug)
Arm 1
Experimental
Participants will receive subcutaneous (SC) mosunetuzumab + CC-220 (dose escalation only) or SC mosunetuzumab + CC-99282.
干预措施: Iberdomide (Drug)
结局指标
主要结局
Percentage of participants with dose-limiting toxicities (DLTs) [dose escalation]
时间窗: Until 90 days after the final dose of study treatment
Percentage of participants with adverse events [all cohorts]
时间窗: Until 90 days after the final dose of study treatment
Best overall response rate (ORR), defined as the proportion of participants whose best overall response is a partial response (PR) or a complete response (CR) during the study, as determined by the investigator using Lugano 2014 criteria [dose expansion]
时间窗: Up to 2 years after start of primary study treatment
Tolerability, as assessed by the incidence of dose interruptions, dose reductions, dose intensity, and treatment discontinuation [dose escalation]
时间窗: Until 90 days after the final dose of study treatment
次要结局
- Best CR rate, defined as the proportion of participants whose best overall response is a CR during the study, as determined by the investigator using Lugano 2014 criteria [all cohorts](Up to 1 year after primary study treatment)
- Best ORR (CR or PR at any time) on study as determined by the investigator using Lugano 2014 criteria [dose escalation](Up to 2 years after primary study treatment)
- Duration of response (DOR) as determined by the investigator using Lugano 2014 criteria [all cohorts](Up to 2 years after primary study treatment)
- Progression-free survival (PFS) as determined by the investigator using Lugano 2014 criteria [dose expansion](Up to 2 years after primary study treatment)
- Event-free survival (EFS) as determined by the investigator using Lugano 2014 criteria [dose expansion](Up to 2 years after primary study treatment)
- Overall survival (OS) [dose expansion](Up to 2 years after primary study treatment)
- Percentage of participants with adverse events [dose expansion](Until 90 days after the final dose of study treatment)
- Serum concentration of intravenous (IV) glofitamab [all cohorts](Up to 2 years after primary study treatment)
- Serum concentration of subcutaneous (SC) mosunetuzumab [all cohorts](Up to 2 years after primary study treatment)
- Serum concentration of CC-220 and CC-99282 (CELMoDs) [all cohorts](Up to 12 cycles of study treatment (cycle length = 21 or 28 days for Arm 1 and 21 days for Arm 2))
- Tolerability, as assessed by the incidence of dose interruptions, dose reductions, dose intensity, and treatment discontinuation [dose expansion](Until 90 days after the final dose of study treatment)
研究者
研究点 (39)
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