NCT03287908终止1 期
A Phase 1/2 Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 701 Monotherapy, or in Combination With Pomalidomide, With and Without Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma (ParadigMM-1B)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Amgen
- 入组人数
- 174
- 试验地点
- 34
- 主要终点
- Number of subjects with clinically-significant changes in vital signs
研究概览
简要总结
The primary purpose of the phase 1 part of the study is to evaluate safety and tolerability of AMG 701 monotherapy to identify the RP2D for AMG 701 monotherapy followed by a dose-confirmation part to gather further safety data for AMG 701 monotherapy at the RP2D in adult subjects with relapsed/refractory multiple myeloma (RRMM). In addition, this study will include a sequential dose exploration part to identify the RP2D of AMG 701 in combination with pomalidomide, with and without dexamethasone (AMG 701-P+/-d). Phase 2 will consist of the dose-expansion part to gain further efficacy and safety experience with AMG 701 monotherapy in adult subjects with RRMM.
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
- •Multiple myeloma meeting the following criteria:
- •Pathologically-documented diagnosis of multiple myeloma that is relapsed or is refractory as defined by the following:
- •Relapsed after > or = 3 lines of prior therapy that must include all approved and available therapies deemed eligible by the investigator, inclusing at a minimum of a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and, where approved and available, a CD38-directed cytolytic antibody in combination in the same line or separate lines of treatment OR refractory to PI, IMiD, and CD38- directed cytolytic antibody,
- •Subjects who could not tolerate a PI, IMiDs, or a CD38-directed cytolytic antibody are eligible to enroll in the study.
- •Measurable disease as per IMWG response criteria
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
- •Inclusion criteria specific to AMG 701-P±d include:
- •Subjects must have received ≥ 2 lines of prior therapy that must include a proteasome inhibitor (PI), lenalidomide, and where approved and available a CD38-directed antibody. These therapies may be in the same line or separate lines of treatment.
- •Subjects must have responded to at least 1 prior line with at least a PR.
- •Subjects that have previously received pomalidomide must not have been removed from therapy due to toxicity attributable to pomalidomide and must be at least 6 months from their last dose of pomalidomide.
- •Subjects must not have known intolerance to doses of dexamethasone up to 40 mg weekly (20 mg weekly if > 75 years).
排除标准
- •Known extramedullary relapse in the absence of any measurable medullary involvement
- •Known central nervous system involvement by multiple myeloma
- •Autologous stem cell transplantation less than 90 days prior to study day 1
- •Recent history of primary plasma cell leukemia (within last 6 months prior to enrollment) or evidence of primary or secondary plasma cell leukemia at the time of screening
- •Waldenstrom's macroglobulinemia
- •Prior amyloidosis (subjects with multiple myeloma with asymptomatic deposition of amyloid plaques found on biopsy would be eligible if all other criteria are met)
- •Treatment with systemic immune modulators including, but not limited to, nontopical systemic corticosteroids (unless the dose is ≤ 10 mg/day prednisone or equivalent), cyclosporine, and tacrolimus within 2 weeks before study day 1
- •Last anticancer treatment (chemotherapy, IMiD, PI, molecular targeted therapy) < 2 weeks prior to study day 1 or treatment with a therapeutic antibody less than 4 weeks prior to study day 1 as well as systemic radiation therapy within 28 days prior to study day 1 or focal radiotherapy within 14 days prior to study day
- •Prior treatment with any drug or construct that targets BCMA on tumor cells (eg, other bispecific antibody constructs, antibody drug conjugates, or CAR-T cells), other than Group C where prior treatment with GSK2857916 (belantamab mafodotin) is required.
- •Exclusion criteria specific to AMG 701-P±d include:
- •History of serious hypersensitivity associated with thalidomide, pomalidomide, or lenalidomide (> grade 3).
- •Multiple myeloma with IgM subtype.
- •POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
- •Contraindication to pomalidomide or dexamethasone.
- •Glucocorticoid therapy within 14 days prior to randomization that exceeds a cumulative dose of 160 mg of dexamethasone or equivalent dose of other corticosteroids.
- •Treatment with systemic immune modulators including, but not limited to, non-topical systemic corticosteroids (unless the dose is ≤ 10 mg/day prednisone or equivalent), cyclosporine, and tacrolimus within 2 weeks before study day 1 or 4 weeks before study day 1 for Phase 1 dose-confirmation.
- •Female subjects of childbearing potential with a positive pregnancy test assessed within 14 days prior to first dose of study drugs and/or a positive urine pregnancy test within 24 hours prior to first dose. In addition, females of childbearing potential unwilling to undergo pregnancy testing weekly during the first 4 weeks of pomalidomide use followed by pregnancy testing every 4 weeks in females with regular menses or every 2 weeks in females with irregular menstrual cycles.
- •Male subjects with a female partner of childbearing potential and female subjects of childbearing potential who are unwilling to use 2 methods of contraception (1 of which must be highly effective during the study and for an additional 75 days (females) and 135 days (males) after receiving the last dose of AMG 701, or 28 days after the last dose pomalidomide (males and females) or dexamethasone (females), whichever occurs later.
- •Females who are lactating/breastfeeding or who plan to breastfeed while on study through 75 days after receiving the last dose of AMG 701, or 28 days after the last dose pomalidomide or dexamethasone, whichever occurs later.
- •Females planning to become pregnant while on study through 75 days after receiving the last dose of AMG 701 or 28 days after the last dose pomalidomide or dexamethasone, whichever occurs later.
- •Male subjects with a pregnant partner who are unwilling to practice abstinence or use a latex or synthetic condom (even if they have had a vasectomy with medical confirmation of surgical success) during treatment (including during dose interruptions) and for an additional 135 days after the last dose of AMG 701, or 28 days after the last dose pomalidomide, whichever occurs later.
- •Males who are unwilling to abstain from sperm donation while on study through 135 days after receiving the last dose of AMG 701 or 28 days after the last dose pomalidomide, whichever occurs later.
研究组 & 干预措施
AMG 701
Experimental
干预措施: AMG 701 (Drug)
AMG 701 + Pomalidomide
Experimental
干预措施: AMG 701 (Drug)
AMG 701 + Pomalidomide
Experimental
干预措施: Pomalidomide (Drug)
AMG 701 + Pomalidomide + Dexamethasone
Experimental
干预措施: AMG 701 (Drug)
AMG 701 + Pomalidomide + Dexamethasone
Experimental
干预措施: Pomalidomide (Drug)
AMG 701 + Pomalidomide + Dexamethasone
Experimental
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Number of subjects with clinically-significant changes in vital signs
时间窗: 48 months
Number of subjects with clinically-significant changes in electrocardiogram (ECG) measurements
时间窗: 48 months
Number of subjects with dose-limiting toxicities (DLTs)
时间窗: 28 days
Number of subjects with clinically-significant changes in physical examination measurements
时间窗: 48 months
Number of subjects with treatment emergent adverse events (TEAEs)
时间窗: 60 months
Number of subjects with treatment-related adverse events
时间窗: 60 months
Number of subjects with disease-related adverse events
时间窗: 60 months
Number of subjects with clinically-significant changes in clinical laboratory tests
时间窗: 48 months
次要结局
- Pharmacokinetic parameter of AMG 701: Area under the concentration-time curve (AUC)(12 weeks)
- Pharmacokinetic parameter of AMG 701: Time of maximum concentration (Tmax)(12 weeks)
- Anti-tumor activity: Best overall response of very good partial response (VGPR)(48 months)
- Anti-tumor activity: Overall survival(60 months)
- Pharmacokinetic parameter of AMG 701: Trough concentration (Ctrough)(12 weeks)
- Anti-tumor activity: Duration of response(48 months)
- Pharmacokinetic parameter of AMG 701: Maximum concentration (Cmax)(12 weeks)
- Pharmacokinetic parameter of AMG 701: Steady state concentration (Css)(12 weeks)
- Anti-tumor activity: Overall response rate(48 months)
- Anti-tumor activity: Best overall response of complete response (CR)(48 months)
- Anti-tumor activity: Time to response(48 months)
- Anti-tumor activity: Best overall response of stringent complete response (sCR)(48 months)
- Anti-tumor activity: Best overall response of partial response (PR)(48 months)
- Anti-tumor activity: Progression-free survival(48 months)
- Anti-tumor activity: Number of subjects with minimum residual disease negative complete response(48 months)
研究者
研究点 (34)
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