Phase I/Ib, Multi-center, Open-label, Study of Single Agent CJM112, and PDR001 in Combination With LCL161 or CJM112 in Patients With Relapsed and/or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 3
- 主要终点
- Number of patients reporting dose limiting toxicities
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability, and identify the recommended doses of single agent CJM112, and of CJM112 or LCL161 in combination with PDR001, in patients with relapsed and/or refractory multiple myeloma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Must be able to provide written informed consent before any screening procedures.
- •Male or female patients ≥18 years of age.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 to
- •Patients with a confirmed diagnosis of multiple myeloma who have received two or more lines of therapy including an IMiD and PI, and are relapsed and/or refractory to their most recent line of therapy. Patients who have received a prior autologous bone marrow transplant and otherwise meet the inclusion criteria are eligible for this study.
- •Must have measurable disease defined by at least 1 of the following 3 measurements:
- •Serum M-protein ≥ 0.5 g/dL OR
- •Urine M-protein ≥ 200 mg/24 hours OR
- •Serum free light chain (FLC) > 100 mg/L of involved FLC
- •All patients must be willing to undergo a mandatory serial bone marrow aspirate and/or biopsy at screening and subsequently following treatment for the assessment of biomarker/pharmacodynamics and disease status. Exceptions may be considered after documented discussion with Novartis.
- •Other inclusion criteria included in the protocol might apply.
排除标准
- •Use of systemic chronic steroid therapy (≥10mg /day of prednisone or equivalent), or any immunosuppressive therapy within 7 days of first dose of study treatment. Topical, inhaled, nasal, or ophthalmic steroids are allowed.
- •Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers, and completely resected carcinoma in situ of any type.
- •Active, known or suspected autoimmune disease other than patients with vitiligo, residual hypothyroidism only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur.
- •Patients with prior known toxicity attributed to PD-1 or PDL-1 directed therapy, which led to discontinuation of these agents, will be excluded from the PDR001 containing arms of the study.
- •Patients with prior known toxicity from IL-17A directed therapy, which led to discontinuation of the study treatment, will be excluded from CJM112 containing arms of the study.
- •Any of the following clinical laboratory results during screening (i.e., within 28 days before the first dose of study treatment):
- •Absolute neutrophil count (ANC) < 1,000/mm3 without growth factor support within 7 days prior to testing
- •Platelet count < 75,000 mm3 without transfusion support within 7 days prior to testing
- •Bilirubin > 1.5 times the upper limit of the normal range (ULN)
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the ULN
- •Calculated creatinine clearance < 30 ml/min according to Cockcroft-Gault equation Other exclusion criteria included in the protocol might apply.
研究组 & 干预措施
Arm A
Dose escalation of single agent CJM112
干预措施: CJM112 (Drug)
Arm B
Dose escalation of CJM112 in combination with a fixed dose of PDR001
干预措施: PDR001 (Drug)
Arm B
Dose escalation of CJM112 in combination with a fixed dose of PDR001
干预措施: CJM112 (Drug)
Arm C
Dose escalation of LCL161 in combination with a fixed dose of PDR001
干预措施: PDR001 (Drug)
Arm C
Dose escalation of LCL161 in combination with a fixed dose of PDR001
干预措施: LCL161 (Drug)
结局指标
主要结局
Number of patients reporting dose limiting toxicities
时间窗: 2 months
number of patients reporting dose limiting toxicity
The number of patients who experience a treatment-related adverse event after being treated with a single dose of single agent CJM112, or two doses of PDR001 in combination with CJM112 or LCL161
时间窗: 24 months
Number of patients with treatment-related adverse events as assessed by CTCAE v4.0
The number of patients requiring interruptions after a single dose of single agent CJM112, or two doses of PDR001 in combination with CJM112 or LCL161
时间窗: 24 months
Frequency of patients requiring a dose interruption
The number of patients treated with single agent CJM112, or PDR001 in combination with either CJM112 or LCL161, who discontinued treatment
时间窗: 24 months
Frequency of patients discontinuing treatment.
The number of patients requiring a dose reduction after a single dose of single agent CJM112, or two doses of PDR001 in combination with CJM112 or LCL161
时间窗: 24 months
Frequency of patients requiring a dose reduction.
次要结局
- Immunogenicity of PDR001 and CJM112(First 6 months of study treatment)
- Overall Response Rate (ORR)(24 Months)
- Best Overall Response (BOR)(24 Months)
- Progression Free Survival (PFS)(24 Months)
- Disease Control Rate (DCR)(24 Months)
- AUC of PDR001, CJM112 and LCL161(24 months)
- Cmax of PDR001, CJM112 and LCL161(24 months)
- Tmax of PDR001, CJM112 and LCL161(24 months)
- Half-life of PDR001, CJM112 and LCL161(24 months)
- Concentration vs time profile of PDR001, CJM112 and LCL161(24 months)