A Phase Ib Study to Evaluate the Safety and Efficacy of Rocbrutinib in Combination With Rituximab, Gemcitabine, Oxaliplatin (R-GemOx) in Patients With Refractory or Relapsed Diffuse Large B-cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 42
- 试验地点
- 4
- 主要终点
- DLTs
研究概览
简要总结
This is a multicenter, open-label phase Ib study, evaluating the safety, tolerability, preliminary efficacy and PK characteristics of Rocbrutinib (LP-168) combined with R-GemOx in patients with R/R non-GCB DLBCL. Study includes dose escalation part and dose expansion part. In the dose escalation part, a classic "3+3" design will be used to assess the safety of each specified dose combination. Upon completion of a predefined escalation part, the decision on whether to proceed to the dose expansion part will be based on the safety, PK, and efficacy data of the combination regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Patients with relapsed or refractory non-GCB DLBCL.
- •Have at least one measurable lesion according to the Lugano Response Criteria
- •ECOG performance status 0-2 (0-1 for dose escalation part).
- •Life expectancy ≥ 12 weeks.
- •Adequate coagulation function, liver and kidney function, bone marrow hematopoietic function.
- •No plan for autologous/allogeneic hematopoietic stem cell transplantation or chimeric antigen receptor T-cell (CAR-T) therapy.
- •Toxicities from prior anti-tumor therapy have recovered to Grade ≤1 according to NCI CTCAE v5.
- •All male subjects and female subjects of childbearing potential must strictly use medically approved contraception throughout the entire study period. All male subjects must also avoid sperm donation during the above period. For women of childbearing potential, the result of serum pregnancy test must be obtained. Women must be non-lactating
- •Subjects must provide adequate tissue and blood samples for exploratory study. Participation is voluntary, requiring signed informed consent and compliance with the treatment regimen and visit schedule.
排除标准
- •Intolerance to Rocbrutinib or any drug in the combination regimen.
- •Prior treatment with a BTK-targeted therapy; prior treatment with R-GemOx.
- •DLBCL transformed from an indolent lymphoma; diagnosis of high-grade or double-hit DLBCL.
- •Chemotherapy, biologic therapy (except CAR-T), immunotherapy or major surgery within 4 weeks of the first dose of study treatment.
- •Small molecule targeted therapy within 4 weeks or within 5 half-lives (whichever is shorter) of the first dose of study treatment.
- •Herbal or proprietary Chinese medicines with antitumor activity or radiotherapy with a limited field of radiation within 7 days of the first dose of study treatment.
- •History of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) or other organ transplantation, or autologous HSCT (auto-HSCT) or chimeric antigen receptor T-cell (CAR-T) therapy within 90 days of the first dose of study treatment.
- •Current corticosteroid therapy at a dose >20 mg/day prednisone equivalent. The prednisone-equivalent dose must have been stable for at least 4 weeks before Cycle 1 Day
- •Unable to discontinue prohibited medications during the study period (strong or moderate CYP3A inhibitors or inducers, P-gp inhibitors, OATP1B3-sensitive substrates, warfarin or other vitamin K antagonists).
- •Known or suspected CNS involvement by lymphoma.
- •Presence of peripheral neuropathy > Grade
- •Any severe and/or uncontrolled systemic disease, or condition affecting drug swallowing or absorption, that in the investigator's judgment makes the subject unsuitable for the study.
研究组 & 干预措施
Dose Level 2
Patients will receive Rocbrutinib at 200 mg once daily in combination with R-GemOx
干预措施: R-GemOx (Drug)
Dose Level 1
Patients will receive Rocbrutinib at 150 mg once daily in combination with R-GemOx
干预措施: R-GemOx (Drug)
Dose Level 1
Patients will receive Rocbrutinib at 150 mg once daily in combination with R-GemOx
干预措施: Rocbrutinib (Drug)
Dose Level 2
Patients will receive Rocbrutinib at 200 mg once daily in combination with R-GemOx
干预措施: Rocbrutinib (Drug)
结局指标
主要结局
DLTs
时间窗: At the end of Cycle 1 (the length of cycle 1 is 21 days)
Dose-Limiting Toxicities
MTD
时间窗: At the end of Cycle 1 (the length of cycle 1 is 21 days)
Maximum Tolerated Dose
Adverse events as assessed by CTCAE v5.0
时间窗: From the first administration to 28 days after the last administration
次要结局
- DoR(Up to approximately two years)
- ORR(Up to approximately two years)
- TTR(Up to approximately two years)
- PFS(Up to approximately two years)
- OS(Up to approximately two years)
- Cmax(From 1 hour prior to administration to 24 hours post-dose)
- Tmax(From 1 hour prior to administration to 24 hours post-dose)
- AUC0-t(From 1 hour prior to administration to 24 hours post-dose)
- t1/2(From 1 hour prior to administration to 24 hours post-dose)