A Phase 1/2 Multicenter, Open-label Study to Assess the Safety, Pharmacokinetics and Efficacy of CC-92480 Monotherapy and in Combination With Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma
概览
- 阶段
- 1 期
- 干预措施
- CC-92480
- 疾病 / 适应症
- Multiple Myeloma
- 发起方
- Celgene
- 入组人数
- 200
- 试验地点
- 54
- 主要终点
- Adverse Events (AEs)
- 状态
- 终止
- 最后更新
- 2个月前
概览
简要总结
This is an open-label, multi-center, international, Phase 1/2 study to assess the safety, PK and efficacy of CC-92480 monotherapy and in combination with dexamethasone in subjects with relapsed and refractory multiple myeloma (RRMM).
All eligible subjects must be previously treated with at least 3 prior regimens including lenalidomide, pomalidomide, a proteasome inhibitor and an anti-CD38 antibody and be refractory to their last line of therapy.
研究者
入排标准
入选标准
- •Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
- •Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
- •Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or
- •Subjects must have a documented diagnosis of MM and measurable disease at enrollment. Measurable disease is defined as:
- •M-protein quantities ≥ 0.5 g/dL by sPEP or
- •≥ 200 mg/24 hour urine collection by uPEP or
- •Serum FLC levels \> 100 mg/L (milligrams/liter) involved light chain and an abnormal kappa/lambda (κ/λ) ratio in subjects without measurable serum or urine M-protein or
- •For subjects with immunoglobulin class A (IgA), myeloma whose disease can only be reliably measured by quantitative immunoglobulin measurement, a serum IgA level ≥ 0.50 g/dL.
- •All subjects must have:
排除标准
- •Subject has a significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
- •Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
- •Subject has any condition that confounds the ability to interpret data from the study.
- •Subject has non-secretory multiple myeloma.
- •Subject has refractory primary multiple myeloma (ie, no history of at least a minor response to a prior treatment regimen).
- •Subject has plasma cell leukemia or active leptomeningeal myelomatosis.
- •Subject has documented, systemic light chain amyloidosis or Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes (POEMS) Syndrome.
- •Subject has immunoglobulin class M (IgM) myeloma.
- •Part 1: Subject has a history of allogeneic bone marrow transplantation. Part 2: Subject has a history of allogeneic bone marrow transplantation within 6 months prior to first dose. Subject should not have ongoing graft-versus-host disease (GVHD) requiring systemic immunosuppression.
- •Subject is undergoing dialysis.
研究组 & 干预措施
Administration of CC-92480 in combination with dexamethasone
Part 1: Escalating doses of CC-92480 plus a fixed dose of dexamethasone Part 2: RP2D of CC-92480 in combination with dexamethasone
干预措施: CC-92480
Administration of CC-92480 in combination with dexamethasone
Part 1: Escalating doses of CC-92480 plus a fixed dose of dexamethasone Part 2: RP2D of CC-92480 in combination with dexamethasone
干预措施: Dexamethasone
Administration of CC-92480 monotherapy
Escalating doses of CC-92480 Monotherapy administered according to different dosing schedules
干预措施: CC-92480
结局指标
主要结局
Adverse Events (AEs)
时间窗: From enrollment until at least 28 days after completion of study treatment
Number of participants with AEs to CC-92480 and/or dexamethasone (Type, frequency, seriousness, severity and relationship of AEs to CC-92480 and dexamethasone; changes from baseline in clinically-relevant physical findings, vital signs, selected laboratory analytes, ECGs).
Pharmacokinetics- AUC
时间窗: Up to approximately 28 days
Area under the plasma concentration-time curve
Pharmacokinetics- Cmax
时间窗: Up to approximately 28 days
Maximal plasma concentration
Pharmacokinetics- Tmax
时间窗: Up to approximately 28 days
Time to Cmax
Pharmacokinetics- t1/2
时间窗: Up to approximately 28 days
Terminal-phase elimination half-life
Pharmacokinetics- CL/F
时间窗: Up to approximately 28 days
Apparent total clearance of the drug from plasma after oral administration
Pharmacokinetics- Vz/F
时间窗: Up to approximately 28 days
Apparent volume of distribution during terminal phase after non-intravenous administration
Maximum tolerated dose (MTD)
时间窗: Up to approximately 28 days
The highest dose of CC-92480 in combination with dexamethasone associated acceptable safety and tolerability.
Overall Response Rate (ORR)
时间窗: Up to approximately 3 years
Overall response rate (ORR) of CC-92480 in combination with dexamethasone in Part 2
次要结局
- Time to response (TTR)(Up to approximately 3 years)
- Duration of response (DOR)(Up to approximately 3 years)
- Progression free survival(Up to approximately 3 years)
- Overall survival (OS)(Up to approximately 3 years)
- Adverse Events (AEs)(Time from first dose of CC-92480 to death due to any cause)
- Overall response rate (ORR)(Up to approximately 3 years)