A Single-arm, Open-label, Phase 2 Study Evaluating Subcutaneous Administration of Isatuximab, Administered by an On Body Delivery System, in Combination With Weekly Carfilzomib and Dexamethasone in Adult Participants With Relapsed and/or Refractory Multiple Myeloma (RRMM)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Sanofi
- 入组人数
- 64
- 试验地点
- 59
- 主要终点
- Overall response rate (ORR)
研究概览
简要总结
The primary purpose of this study is to assess the efficacy (overall response rate) of subcutaneous (SC) via on body delivery system (SC-OBDS) isatuximab in combination with weekly carfilzomib and dexamethasone (Kd) in adult participants with RRMM having received 1 to 3 prior lines of therapy.
详细描述
The duration of the study for a participant will include a period for screening of up to 28 days, a study treatment period of 12 months (except early discontinuation), the end-of-treatment (EOT) visit about 30 days after the last dose of study treatment, and a study follow-up period until death or the final study cut-off date. A cycle duration is 28 days. After study treatment discontinuation, participants will return to the study site 30 days after the last dose of study treatment for the EOT visit or before further anti-myeloma therapy initiation, whichever comes first.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Participants must have a documented diagnosis of MM.
- •Participants with measurable disease defined as at least one of the following:
- •Serum M-protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis and/or
- •Urine M-protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis and/or
- •Serum free light chain (FLC) assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65).
- •Participants with relapsed and/or refractory MM with at least 1 prior line of therapy and no more than 3 prior lines of therapy.
- •Contraceptive use by [men and women] should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •Male participants agree to practice true abstinence or agree to use contraception while receiving study treatment, during dose interruptions and at least 5 months following study treatment discontinuation, even if has undergone a successful vasectomy.
- •A female participant is eligible to participate if she is not pregnant, not breastfeeding, and either is not a female of childbearing potential (FCBP XE " FCBP " \f Abbreviation \t "female of childbearing potential" ) or agrees to practice complete abstinence or use contraception.
- •Capable of giving signed informed consent.
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Primary refractory MM defined as participants who have never achieved at least a minimal response (MR) with any treatment during the disease course.
- •Participants with prior anti-CD38 treatment if: a) administered < 6 months before first isatuximab administration or, b) intolerant to the anti-CD38 previously received.
- •Participants who are refractory to carfilzomib.
- •Known history of allergy to captisol (a cyclodextrin derivative used to solubilize carfilzomib), prior hypersensitivity to sucrose, histidine (as base and hydrochloride salt), polysorbate 80, or any of the components (active substance or excipient) of study treatment that are not amenable to premedication with steroids, or intolerance to arginine and Poloxamer 188 that would prohibit further treatment with these agents.
- •Participants with contraindication to dexamethasone and/or to carfilzomib.
- •Any anti-myeloma drug treatment within 14 days before the first isatuximab administration, including dexamethasone.
- •Prior allogenic HSC transplant with active graft versus host disease (GvHD XE " GvHD " \f Abbreviation \t "graft versus host disease" ) (GvHD any grade and/or being under immunosuppressive treatment within the last 2 months).
- •Any major procedure within 14 days before the first isatuximab administration: plasmapheresis, major surgery (kyphoplasty is not considered a major procedure), radiotherapy.
- •Vaccination with a live vaccine within 4 weeks before the first isatuximab administration. Seasonal flu vaccines that do not contain live virus are permitted.
- •Participant not suitable for participation, whatever the reason, as judged by the Investigator, including medical or clinical conditions, or participants potentially at risk of noncompliance to study procedures.
- •The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.
研究组 & 干预措施
Isatuximab in combination with weekly carfilzomib and dexamethasone
Participants will receive isatuximab via SC-OBDS administration in combination with weekly carfilzomib and dexamethasone. Isatuximab will be administered on days 1, 8, 15 and 22 for Cycle 1 and then on days 1, 15 for subsequent cycles. Carfilzomib will be administered intravenously (IV) at a starting dose on Day 1 of Cycle 1 and then escalated dose on Days 8 and 15 of Cycle 1, followed by Days 1, 8 and 15 of subsequent cycles. Dexamethasone will be given on Days 1, 8, 15, and 22 of Cycle 1 and then on Days 1, 8 and 15 of subsequent cycles. Dexamethasone will be administered IV on Cycle 1 Day 1, and IV or PO in the subsequent administrations. 1 cycle = 28 days.
干预措施: Isatuximab SC-OBDS (Drug)
Isatuximab in combination with weekly carfilzomib and dexamethasone
Participants will receive isatuximab via SC-OBDS administration in combination with weekly carfilzomib and dexamethasone. Isatuximab will be administered on days 1, 8, 15 and 22 for Cycle 1 and then on days 1, 15 for subsequent cycles. Carfilzomib will be administered intravenously (IV) at a starting dose on Day 1 of Cycle 1 and then escalated dose on Days 8 and 15 of Cycle 1, followed by Days 1, 8 and 15 of subsequent cycles. Dexamethasone will be given on Days 1, 8, 15, and 22 of Cycle 1 and then on Days 1, 8 and 15 of subsequent cycles. Dexamethasone will be administered IV on Cycle 1 Day 1, and IV or PO in the subsequent administrations. 1 cycle = 28 days.
干预措施: Montelukast (Drug)
Isatuximab in combination with weekly carfilzomib and dexamethasone
Participants will receive isatuximab via SC-OBDS administration in combination with weekly carfilzomib and dexamethasone. Isatuximab will be administered on days 1, 8, 15 and 22 for Cycle 1 and then on days 1, 15 for subsequent cycles. Carfilzomib will be administered intravenously (IV) at a starting dose on Day 1 of Cycle 1 and then escalated dose on Days 8 and 15 of Cycle 1, followed by Days 1, 8 and 15 of subsequent cycles. Dexamethasone will be given on Days 1, 8, 15, and 22 of Cycle 1 and then on Days 1, 8 and 15 of subsequent cycles. Dexamethasone will be administered IV on Cycle 1 Day 1, and IV or PO in the subsequent administrations. 1 cycle = 28 days.
干预措施: Dexamethasone (Drug)
Isatuximab in combination with weekly carfilzomib and dexamethasone
Participants will receive isatuximab via SC-OBDS administration in combination with weekly carfilzomib and dexamethasone. Isatuximab will be administered on days 1, 8, 15 and 22 for Cycle 1 and then on days 1, 15 for subsequent cycles. Carfilzomib will be administered intravenously (IV) at a starting dose on Day 1 of Cycle 1 and then escalated dose on Days 8 and 15 of Cycle 1, followed by Days 1, 8 and 15 of subsequent cycles. Dexamethasone will be given on Days 1, 8, 15, and 22 of Cycle 1 and then on Days 1, 8 and 15 of subsequent cycles. Dexamethasone will be administered IV on Cycle 1 Day 1, and IV or PO in the subsequent administrations. 1 cycle = 28 days.
干预措施: Acetaminophen (Drug)
Isatuximab in combination with weekly carfilzomib and dexamethasone
Participants will receive isatuximab via SC-OBDS administration in combination with weekly carfilzomib and dexamethasone. Isatuximab will be administered on days 1, 8, 15 and 22 for Cycle 1 and then on days 1, 15 for subsequent cycles. Carfilzomib will be administered intravenously (IV) at a starting dose on Day 1 of Cycle 1 and then escalated dose on Days 8 and 15 of Cycle 1, followed by Days 1, 8 and 15 of subsequent cycles. Dexamethasone will be given on Days 1, 8, 15, and 22 of Cycle 1 and then on Days 1, 8 and 15 of subsequent cycles. Dexamethasone will be administered IV on Cycle 1 Day 1, and IV or PO in the subsequent administrations. 1 cycle = 28 days.
干预措施: Diphenhydramine (Drug)
Isatuximab in combination with weekly carfilzomib and dexamethasone
Participants will receive isatuximab via SC-OBDS administration in combination with weekly carfilzomib and dexamethasone. Isatuximab will be administered on days 1, 8, 15 and 22 for Cycle 1 and then on days 1, 15 for subsequent cycles. Carfilzomib will be administered intravenously (IV) at a starting dose on Day 1 of Cycle 1 and then escalated dose on Days 8 and 15 of Cycle 1, followed by Days 1, 8 and 15 of subsequent cycles. Dexamethasone will be given on Days 1, 8, 15, and 22 of Cycle 1 and then on Days 1, 8 and 15 of subsequent cycles. Dexamethasone will be administered IV on Cycle 1 Day 1, and IV or PO in the subsequent administrations. 1 cycle = 28 days.
干预措施: Methylprednisolone (Drug)
Isatuximab in combination with weekly carfilzomib and dexamethasone
Participants will receive isatuximab via SC-OBDS administration in combination with weekly carfilzomib and dexamethasone. Isatuximab will be administered on days 1, 8, 15 and 22 for Cycle 1 and then on days 1, 15 for subsequent cycles. Carfilzomib will be administered intravenously (IV) at a starting dose on Day 1 of Cycle 1 and then escalated dose on Days 8 and 15 of Cycle 1, followed by Days 1, 8 and 15 of subsequent cycles. Dexamethasone will be given on Days 1, 8, 15, and 22 of Cycle 1 and then on Days 1, 8 and 15 of subsequent cycles. Dexamethasone will be administered IV on Cycle 1 Day 1, and IV or PO in the subsequent administrations. 1 cycle = 28 days.
干预措施: Carfilzomib (Drug)
结局指标
主要结局
Overall response rate (ORR)
时间窗: 6 months after the Last Participant In (LPI) i.e., approximately 32 months
ORR, defined as the proportion of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR), according to IMWG criteria assessed by investigator.
次要结局
- Number of participants with infusion reactions (IRs)(From the signing of informed consent to 30 days after the date of the last study treatment administration i.e., approximately 38 months)
- Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and laboratory abnormalities (per NCI-CTCAE grade or PCSA if NCI-CTCAE scale is not applicable)(From the signing of informed consent to 30 days after the date of the last study treatment administration i.e., approximately 38 months)
- Number of participants with injection site reactions (ISRs)(From the signing of informed consent to 30 days after the date of the last study treatment administration i.e., approximately 38 months)
- CR or better(12 months after the Last Participant In (LPI) i.e., approximately 38 months)
- VGPR or better(12 months after the Last Participant In (LPI) i.e., approximately 38 months)
- Duration of response (DOR)(12 months after the Last Participant In (LPI) i.e., approximately 38 months)
- Time to first response (TT1R)(12 months after the Last Participant In (LPI) i.e., approximately 38 months)
- Time to best response (TTBR)(12 months after the Last Participant In (LPI) i.e., approximately 38 months)
- Patient experience and Satisfaction Questionnaire v2 (PESQ v2)(Cycle 3/Day 15 and Cycle 6/Day 15)
- Positivity titer of anti-drug antibodies (ADA) in a subset of approximately 30 participants(From Cycle 1 Day 1 to follow-up (90 days from last administration) i.e, approximately up to 15 months (1 cycle = 28 days))
- Maximum observed concentration (Cmax) of isatuximab in a subset of approximately 30 participants(Multiple timepoints in Cycle 1 (1 cycle = 28 days))
- Cumulative area under the curve over the first 4 weeks of isatuximab treatment (AUC4 weeks) in a subset of approximately 30 participants(Multiple timepoints in Cycle 1 (1 cycle = 28 days))