2022-502616-37-00
招募中
1/2 期
An Open-Label, Phase I/II Study to Evaluate the Safety, Pharmacokinetics and Preliminary Anti-Tumor Activity of Englumafusp Alfa (RO7227166, a CD19 Targeted 4-1BB Ligand) in Combination with Obinutuzumab and in Combination with Glofitamab Following a Pre-Treatment Dose of Obinutuzumab Administered in Participants with Relapsed/Refractory B-Cell Non-Hodgkin’s Lymphoma
概览
- 阶段
- 1/2 期
- 干预措施
- 未指定
- 疾病 / 适应症
- 未指定
- 发起方
- F. Hoffmann-La Roche AG
- 入组人数
- 194
- 试验地点
- 17
- 主要终点
- Part I/II 1. Nature and frequency of dose-limiting toxicities (DLTs)
- 状态
- 招募中
- 最后更新
- 去年
概览
简要总结
Part I/II (Dose-Escalation)
-
- To determine the maximum tolerated dose and/ or recommended Phase 2 dose (RP2D) of englumafusp alfa in combination with obinutuzumab and in combination with glofitamab following obinutuzumab pre-treatment (GpT) or double GpT (DGpT) in participants with r/r B-cell NHL (Part I and IIA) and in participants with r/r MCL and Richter’s transformation (Part IIB)
- To evaluate the safety and tolerability of englumafusp alfa in combination with obinutuzumab and in combination with glofitamab following GpT or DGpT in participants with r/r B-cell NHL (Part I and IIA) and in participants with r/r MCL and Richter’s transformation (Part IIB) Part III (Dose-Expansion)
- A1: To compare anti-tumor activity of englumafusp alfa at selected doses (in combination with glofitamab and glofitamab monotherapy) in participants with r/r large B-cell lymphoma (LBCL)
- A2 and B: To demonstrate anti- tumor activity of englumafusp alfa in combination with glofitamab in r/r follicular lymphoma (FL) and MCL
研究者
Trial Information System - TISL
Scientific
F. Hoffmann-La Roche AG
入排标准
入选标准
- •Willing and able to comply with protocol-mandated hospitalization per protocol. Participants must also be willing to comply with all study-related procedures
- •A history or status of: - a histologically-confirmed hematological malignancy that is expected to express CD19 and CD20; - certain B-cell malignancies with relapse after or failure to respond to at least one prior treatment regimen for Part I and II - certain B-cell malignancies with relapse after or failure to respond to only one prior systemic treatment regimen for Part 3 - no available treatment options that are expected to prolong survival
- •Must have at least one measureable target lesion (>= 1.5 cm) in its largest dimension by computed tomography scan
- •Able and willing to provide a fresh biopsy from a safely accessible site, per Investigator’s determination, providing the participant has more than one measurable target lesion. However, in the absence of fresh biopsy, provide the most recent archival tumor tissue samples that are preferably not older than 6 months and preferably not confounded by major events. For archival biopsies formalin-fixed, paraffin-embedded blocks are preferred, but if not available, unstained slides are acceptable
- •Eastern Cooperative Oncology Group performance status of 0 or 1
- •Life expectancy of >= 12 weeks
排除标准
- •Circulating lymphoma cells, defined by out of range (high) absolute lymphocyte count or the presence of abnormal cells in the peripheral blood signifying circulating lymphoma cells
- •Participants with acute bacterial, viral, or fungal infection at baseline, confirmed by a positive blood culture within 72 hours prior to obinutuzumab infusion or by clinical judgment in the absence of a positive blood culture
- •Participants with known active infection, or reactivation of a latent infection, whether bacterial, viral fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics
- •Prior treatment with systemic immunotherapeutic agents, including, but not limited to, radio-immunoconjugates, antibody-drug conjugates, immune/cytokines or monoclonal antibodies within 4 weeks or five half-lives of the drug, whichever is shorter, before obinutuzumab infusion on D-7
- •History of treatment-emergent immune-related AEs associated with prior immunotherapeutic agents and auto-immune disease - Grade >= 3 AEs with the exception of Grade 3 endocrinopathy managed with replacement therapy and Grade 3 CRS which has fully resolved - Grade 1-2 AEs that did not resolve to baseline after treatment discontinuation
- •Treatment with standard radiotherapy, any chemotherapeutic agent, or treatment with any other investigational or approved anti-cancer agent within 4 weeks or 5 half-lives of the drug, whichever is shorter, prior to obinutuzumab infusion
结局指标
主要结局
Part I/II 1. Nature and frequency of dose-limiting toxicities (DLTs)
Part I/II 1. Nature and frequency of dose-limiting toxicities (DLTs)
Part I/II 2. Incidence, nature, and severity of adverse events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 and for CRS the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading
Part I/II 2. Incidence, nature, and severity of adverse events (AEs) graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 and for CRS the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading
Part III 3. Investigator assessed CR rate as assessed by FDG-PET/CT scan
Part III 3. Investigator assessed CR rate as assessed by FDG-PET/CT scan
次要结局
- Part I/II 1. Total exposure (area under the concentration time curve [AUC]) of englumafusp alfa in combination with obinutuzumab and glofitamab
- Part I/II 2. Maximum serum concentration (peak concentration, Cmax) of englumafusp alfa in combination with obinutuzumab and glofitamab
- Part I/II 3. Minimum serum concentration (trough concentration, Cmin) of englumafusp alfa in combination with obinutuzumab and glofitamab
- Part I/II 4. Clearance (CL), Volume of distribution of steady state (Vss) and half-life (t½) if data permit
- Part I/II 5. Analysis of dose-linearity in exposure
- Part I/II 6. Additional PK parameters may be determined as appropriate
- Part I/II 7. Incidence and titer of englumafusp alfa anti-drug antibodies (ADAs) during the study relative to prevalence of ADAs at baseline
- Part I/II 8. Overall response rate (ORR)
- Part I/II 9. Disease control rate (DCR)
- Part III 10. Incidence, nature, and severity of AEs graded according to the NCI CTCAE v5.0 and for CRS the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading
- Part III 11. Total exposure (area under the concentration time curve [AUC]) of englumafusp alfa in combination with glofitamab
- Part III 12. Maximum serum concentration (peak concentration, Cmax) of englumafusp alfa in combination with glofitamab
- Part III 13. Minimum serum concentration (trough concentration, Cmin) of englumafusp alfa in combination with glofitamab
- Part III 14. Clearance (CL), Volume of distribution of steady state (Vss) and half-life (t½) if data permit of englumafusp alfa in combination with glofitamab
- Part III 15. Analysis of dose-linearity in exposure
- Part III 16. Additional PK parameters may be determined as appropriate
- Part III 17. Incidence and titer of englumafusp alfa anti-drug antibodies (ADAs) during the study relative to prevalence of ADAs at baseline
- Part III 18. Overall response rate (ORR)
- Part III 19. Duration of complete response (DOCR)
- Part III 20. Progression-free survival (PFS)
- Part III 21. Overall survival (OS)
- Part III 22.Time to first complete response (TFCR)
- Part III 23. Time to first overall response (TFOR)
- Part III 24 Change from baseline in physical function, role function, and HRQoL based on EORTC QLQ C30
- Part III 25. Change from baseline in disease-related symptoms based on the FACT-Lym Lymphoma scale
- Part III 26. Baseline levels and change from baseline of cellular biomarkers in blood and tumor tissue, using markers of B, and T-cell lineage
- Part I/II 27. Baseline levels and change from baseline of cellular biomarkers in blood, using markers of B-, T- and NK-cell lineage
研究点 (17)
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