An Open-Label, Multicenter, Phase Ib/II Trial Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Mosunetuzumab (BTCT4465A) in Combination with Polatuzumab Vedotin in Patients with B-Cell Non-Hodgkin Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 17
- 试验地点
- 8
- 主要终点
- 1. Occurrence and severity of adverse events, including DLTs (Phase Ib)
研究概览
简要总结
Phase Ib To evaluate the safety and tolerability of mosunetuzumab (Mosun) + polatuzumab vedotin (Pola) in patients with relapsed or refractory (R/R) DLBCL or follicular lymphoma (FL), including estimation of maximum tolerated dose, determination of recommended Phase II dose (RP2D), characterization of dose-limiting toxicity (DLT) To make a preliminary assessment of the anti-tumor activity of Mosun + Pola Phase II: To evaluate the efficacy of Mosun (IV) plus Pola in patients with R/R FL and R/R DLBCL, based on best objective response rate (ORR) in the study, as determined by the Independent Review Committee (IRC) To evaluate the efficacy of Mosun (SC) plus Pola in patients with R/R DLBCL and R/R MCL based on best ORR in the study, as determined by the Independent Review Committee (IRC)
研究设计
- 分配方式
- Randomized
- 主要目的
- Go40516 - Open Label, Multicenter, Phase Ib/ii Trial
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years at time of signing Informed Consent Form
- •Patients must have histologically confirmed R/R FL, DLBCL, or MCL
- •For DLBCL or FL, must have received at least one prior systemic treatment regimen containing an anti- cluster of differentiation 20 (CD20) - directed therapy
- •For MCL, must have received at least two prior systemic treatment regimens which include agents from all three classes below: anti-CD20-directed therapy, a Bruton’s tyrosine kinase (BTK) inhibitor, and an anthracycline or bendamustine
- •Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2
- •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.
- •Patients must have histologically confirmed R/R FL, DLBCL, or MCL
- •For DLBCL or FL, must have received at least one prior systemic treatment regimen containing an anti- cluster of differentiation 20 (CD20) - directed therapy
- •For MCL, must have received at least two prior systemic treatment regimens which include agents from all three classes below: anti-CD20-directed therapy, a Bruton’s tyrosine kinase (BTK) inhibitor, and an anthracycline or bendamustine
- •Age ≥ 18 years at time of signing Informed Consent Form
- •Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2
- •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.
排除标准
- •Current eligibility for autologous SCT in patients with R/R DLBCL, R/R transformed FL, or R/R Grade 3b FL
- •Current > Grade 1 peripheral neuropathy
- •Prior use of any monoclonal antibodies, radioimmunoconjugates or antibody-drug conjugates for anti-lymphoma treatment within 4 weeks before first dose of study treatment
- •Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
- •Pregnant or lactating women
- •Prior treatment with Mosun or other CD20-directed bispecific antibodies or with Pola
- •Current > Grade 1 peripheral neuropathy
- •Prior use of any monoclonal antibodies, radioimmunoconjugates or antibody-drug conjugates for anti-lymphoma treatment within 4 weeks before first dose of study treatment
- •Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
- •Current eligibility for autologous SCT in patients with R/R DLBCL, R/R transformed FL, or R/R Grade 3b FL
- •Pregnant or lactating women
- •Prior treatment with Mosun or other CD20-directed bispecific antibodies or with Pola
研究组 & 干预措施
RoActemra 20 mg/mL concentrate for solution for infusion
干预措施: RoActemra 20 mg/mL concentrate for solution for infusion (Drug)
PARACETAMOL
干预措施: PARACETAMOL (Drug)
MabThera 500 mg concentrate for solution for infusion
干预措施: MabThera 500 mg concentrate for solution for infusion (Drug)
Polivy 140 mg powder for concentrate for solution for infusion.
干预措施: Polivy 140 mg powder for concentrate for solution for infusion. (Drug)
FLUDEOXYGLUCOSE (18F)
干预措施: FLUDEOXYGLUCOSE (18F) (Drug)
METHYLPREDNISOLONE
干预措施: METHYLPREDNISOLONE (Drug)
PEGFILGRASTIM
干预措施: PEGFILGRASTIM (Drug)
ALLOPURINOL
干预措施: ALLOPURINOL (Drug)
PREDNISONE
干预措施: PREDNISONE (Drug)
DEXAMETHASONE
干预措施: DEXAMETHASONE (Drug)
RASBURICASE
干预措施: RASBURICASE (Drug)
DIPHENHYDRAMINE
干预措施: DIPHENHYDRAMINE (Drug)
Mosunetuzumab, Mosunetuzumab, Mosunetuzumab, Mosunetuzumab
干预措施: Mosunetuzumab (Drug)
结局指标
主要结局
1. Occurrence and severity of adverse events, including DLTs (Phase Ib)
1. Occurrence and severity of adverse events, including DLTs (Phase Ib)
2. Change from baseline in targeted vital signs (Phase Ib)
2. Change from baseline in targeted vital signs (Phase Ib)
3. Change from baseline in targeted clinical laboratory test results (Phase Ib)
3. Change from baseline in targeted clinical laboratory test results (Phase Ib)
4. CR rate at the time of PRA as determined by the investigator (Phase Ib)
4. CR rate at the time of PRA as determined by the investigator (Phase Ib)
5. Best ORR as determined by the investigator (Phase Ib)
5. Best ORR as determined by the investigator (Phase Ib)
6. DOR as determined by the investigator (Phase Ib)
6. DOR as determined by the investigator (Phase Ib)
7. Best ORR, as determined by the IRC (Phase II)
7. Best ORR, as determined by the IRC (Phase II)
次要结局
- 11. Change from baseline in targeted clinical laboratory test results (Phase II)
- 12. Maximum serum concentration (Cmax) for Mosun (Phase Ib and II)
- 13. Minimum serum concentration (Cmin) for Mosun (Phase Ib and II)
- 14. Total exposure area under the concentration-time curve (AUC) for Mosun (Phase Ib and II)
- 15. Clearance for Mosun (Phase Ib and II)
- 16. Volume of distribution for Mosun (Phase Ib and II)
- 17. Relationship between ADA status and efficacy, safety, pharmacokinetics, and biomarkers (Phase Ib and II)
- 1. Best ORR as determined by the investigator (Phase II)
- 2. Best CR rate as determined by the investigator and IRC (Phase II)
- 3. CR rate at the time of PRA as determined by the investigator and IRC (Phase II)
- 4. ORR at the time of PRA as determined by the investigator and IRC (Phase II)
- 5. DOR as determined by the investigator and IRC (Phase II)
- 6. PFS as determined by the investigator and IRC (Phase II)
- 7. EFS as determined by the investigator and IRC (Phase II)
- 8. OS (Phase II)
- 9. Occurrence and severity of adverse events (Phase II)
- 10. Change from baseline in targeted vital signs (Phase II)
研究者
Trial Information Support Line - TISL
Scientific
F. Hoffmann-La Roche AG