A Multicenter, Open-Label, Phase I/II Study to Evaluate the Safety, Efficacy, Tolerability and Pharmacokinetics of Escalating Doses of Glofitamab (RO7082859) as a Single Agent and in Combination with Obinutuzumab Administered After a Fixed, Single Dose Pre-Treatment of Obinutuzumab (Gazyva®/Gazyvaro™) in Patients with Relapsed/Refractory B-Cell Non-Hodgkin’s Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 457
- 试验地点
- 22
- 主要终点
- 1. Incidence of dose-limiting toxicity (DLTs)
研究概览
简要总结
To determine: the maximal tolerated dose or optimal biologic dose and dose-limiting toxicity of glofitamab as single agent and in combination with obinutuzumab following Gpt in patients with r/r NHL a recommended dose and schedule of glofitamab as single agent and in combination with obinutuzumab following Gpt To evaluate: The safety, tolerability, and pharmacokinetic (PK) of glofitamab as single agent and in combination with obinutuzumab following obinutuzumab pretreatment (Gpt) in patients with r/r (CD)20 + B-cell NHL The efficacy of glofitamab as single agent following Gpt in patients in patients with Diffuse large B-cell lymphoma, and in patients with r/r Follicular lymphoma (FL) measured by Independent Review Committee (IRC)-assessed complete response rate (CRR) according to Lugano 2014 Classification To evaluate the efficacy of glofitamab as single agent following Gpt and/or dGpt in R/R MCL patients by IRC-assessed CRR according to Lugano Classification
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Part Iii: Does Expansion Cohorts
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Patient willing and able to comply with protocol-mandated hospitalizations upon administration of glofitamab and also all study-related procedures, in Part III, this includes completion of Patient-reported outcome
- •For Parts I and II:Grades 1-3b FL; Marginal zone lymphoma; Mantle cell lymphoma; DLBCL; Primary mediastinal B-cell lymphoma; Richter’s transformation; and transformed FL (trFL) For Part III expansion cohorts: DLBCL cohort (r/r DLBCL, not otherwise specified [NOS]/high-grade B-cell lymphoma [HGBCL],PMBCL and trFL). Patients must have relapsed after or failed to respond to at least two prior systemic treatment regimens (including at least one prior regimen containing anthracycline, and at least one containing an anti CD20-directed therapy). cohort: R/R FL cohort: Grades 1-3a FL patients must have relapsed after or failed to respond to at least two prior lines of systemic therapy and must have received prior treatment with rituximab and alkylating agents
- •For Part III expansion cohorts: Life expectancy (in the opinion of the Investigator) of >= 12 weeks
- •Measurable disease, defined as at least one bi-dimensionally measurable nodal lesion, defined as >1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as >1.0 cm in its longest dimension
- •Eastern Cooperative Oncology Group performance status of 0 or 1
- •Adequate liver, hematological, and renal function
排除标准
- •Inability to comply with protocol mandated hospitalization and restrictions
- •Patients with chronic lymphocytic leukemia (CLL), Burkitt lymphoma and lymphoplasmacytic lymphoma
- •Patients with a known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
- •Patients with acute bacterial, viral, or fungal infection at baseline, confirmed by a positive blood culture within 72 hours prior to Gpt infusion or by clinical judgment in the absence of a positive blood culture
- •Patients with known active infection, or reactivation of a latent infection, whether bacterial, viral, fungal, mycobacterial, or other pathogens or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of dosing
- •Pregnant, breast-feeding or intending to become pregnant during the study
结局指标
主要结局
1. Incidence of dose-limiting toxicity (DLTs)
1. Incidence of dose-limiting toxicity (DLTs)
2. The primary safety endpoints will be incidence of all adverse events, changes in vital signs, clinical laboratory values, electrocardiograms and incidence of DLTs
2. The primary safety endpoints will be incidence of all adverse events, changes in vital signs, clinical laboratory values, electrocardiograms and incidence of DLTs
3. Incidence, nature, and severity of all adverse events
3. Incidence, nature, and severity of all adverse events
4. Incidence of cytokine-release related events (cytokine-release syndrome [CRS] and infusion-related reactions [IRRs]) according to the grading criteria in Lee (2014)
4. Incidence of cytokine-release related events (cytokine-release syndrome [CRS] and infusion-related reactions [IRRs]) according to the grading criteria in Lee (2014)
5. Changes in clinical laboratory values: hematology and biochemistry test results
5. Changes in clinical laboratory values: hematology and biochemistry test results
6. Changes in vital signs, including systolic and diastolic blood pressure, respiratory rate, pulse rate, and body temperature
6. Changes in vital signs, including systolic and diastolic blood pressure, respiratory rate, pulse rate, and body temperature
7. Incidence of ECG abnormality
7. Incidence of ECG abnormality
8. Total exposure (area under the concentration-time curve [AUC]) of glofitamab
8. Total exposure (area under the concentration-time curve [AUC]) of glofitamab
9. Maximum serum concentration (Cmax) of glofitamab
9. Maximum serum concentration (Cmax) of glofitamab
10. Minimum serum concentration (Cmin) of glofitamab
10. Minimum serum concentration (Cmin) of glofitamab
11. Clearance (CL) of glofitamab
11. Clearance (CL) of glofitamab
12. Volume of distribution (Vz) of glofitamab
12. Volume of distribution (Vz) of glofitamab
13. Independent Review Committee (IRC)-assessed CR rate using Lugano criteria
13. Independent Review Committee (IRC)-assessed CR rate using Lugano criteria
次要结局
- 1. Investigator (INV)-assessed CR rate (Lugano classification)
- 2. IRC-assessed overall response rate (ORR) (Lugano classification)
- 3. INV-assessed ORR (Lugano classification)
- 4. IRC - and INV-assessed duration of complete response (Lugano Classification)
- 5. IRC- and INV-assessed duration of response (Lugano classification)
- 6. IRC-assessed progression-free survival (PFS) and INV-assessed PFS (Lugano classification)
- 7. IRC-assessed time to first complete response (TFCR) (Lugano classification)
- 8. INV-assessed TFCR (Lugano classification)
- 9. IRC-assessed time to first overall response (TFOR) (Lugano classification)
- 10. INV-assessed TFOR (Lugano classification)
- 11. Overall survival
- 12. Change from baseline in physical function, role function, and health-related quality of life European organization for research and treatment of cancer quality of Life questionnaire core 30 based on European organization for research and treatment of cancer quality of Life questionnaire core 30
- 13. Change from baseline in disease-related symptoms based on the functional assessment of cancer therapy-lymphoma scale
- 14. Incidence of ADA formation and events related to immune complex deposition and activation
研究者
Trial Information System - TISL
Scientific
F. Hoffmann-La Roche AG