A Phase 1b Multicenter, Open-label, Expansion Study to Assess the Safety and Efficacy of AMG 420 as Monotherapy in Subjects With Relapsed and/or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Amgen
- 入组人数
- 23
- 试验地点
- 10
- 主要终点
- Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
研究概览
简要总结
To confirm the maximum tolerated dose (MTD) from the BI 836909 trial of 400 mcg/d, given as 28-day continuous intravenous infusion in patients with relapsed and/or refractory multiple myeloma, to test the 600 mcg/d dose, given as a 28-day continuous iV infusion.
详细描述
Cohort 1 will consist of 10 subjects dosed at 400 mcg/d. Cohort 2 will consist of 10 subjects dosed at 600 mcg/d. All doses will be given as a 28-day continuous IV infusion, followed by a 2 week treatment-free interval, until subject experiences disease progression as per International Myeloma Working Group (IMWG) criteria.
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
- •Subject has provided informed consent prior to initiation of any study specific activities/procedures
- •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 3 or more lines of prior therapy that must include a proteasome inhibitors (PI), an immunomodulators (IMiD), and a CD38-directed monoclonal antibody in any order during the course of treatment OR refractory to a PI, IMiD, and CD38-directed monoclonal antibody.
- •Measurable disease, defined by 1 or more of the following at time of screening: 1) serum M-protein > 0.5 g/dL measured by serum protein electrophoresis (SPEP); 2) urinary M-protein excretion > 200 mg/24 hours; 3) Involved serum free light chain (sFLC ) measurement > 10 mg/dL, provided that the sFLC ratio is abnormal (<0.26 or >1.65) as per IMWG response criteria
- •. ECOG performance status of less than or equal to 2
- •Life expectancy of at least 3 months per PI judgement at screening
- •Hematological function without transfusion support (within 7 days from screening assessment) as follows:
- •ANC ≥ 1.0 x 10^9/L (without growth factor support)
- •platelet count ≥ 25 x 10^9/L (without transfusions)
- •hemoglobin ≥ 7.0 g/dL (transfusions permitted no later than 48 hours before screening)
- •Renal function as follows: calculated or measured creatinine clearance ≥30 mL/min using the Cockcroft-Gault equation or via 24-hour urine collection with plasma and urine creatinine concentrations, respectively
- •Hepatic function as follows: AST and ALT < 3x upper limit of normal (ULN); TBIL <1.5 x ULN (unless considered due to Gilbert's syndrome)
排除标准
- •Known central nervous system involvement by multiple myeloma
- •Evidence of primary or secondary plasma cell leukemia at the time of screening
- •Waldenstrom's macroglobulinemia
- •Unresolved toxicities from prior anticancer therapy, defined as not having resolved to CTCAE version 5.0 grade 1 or to levels dictated in the eligibility criteria with the exception of grade 2 peripheral neuropathy, alopecia, or toxicities from prior anticancer therapy that are considered irreversible (defined as having been present and stable for > 4 weeks) which may be allowed if they are not otherwise described in the exclusion criteria and there is agreement to allow by the PI and Amgen medical monitor
- •History of other malignancy within the past 3 years, with the following exceptions:
- •malignancy treated with curative intent and with no known active disease present for ≥ 1 year before enrollment and felt to be at low risk for recurrence by the treating physician;
- •adequately-treated non-melanoma skin cancer or lentigo maligna without evidence of disease;
- •adequately-treated cervical carcinoma in situ without evidence of disease;
- •breast ductal carcinoma in situ with full surgical resection (ie, negative margins) and without evidence of disease;
- •prostate cancer with a Gleason score < 6 with undetectable PSA over 12 months;
- •treated medullary or papillary thyroid cancer;
- •adequately-treated urothelial papillary noninvasive carcinoma or carcinoma in situ; similar neoplastic conditions with an expectation of > 95% five-year disease-free survival;
- •see exclusion criterion # 2 for exclusion of subjects with evidence of primary or secondary plasma cell leukemia at the time of screening
- •Known history of amyloidosis
- •Current or known history of autoimmune diseases requiring systemic treatment in past 5 years except vitiligo, resolved childhood asthma/atopy, or subjects with history of hypothyroidism after completing treatment for autoimmune thyroid disease, stable on hormone replacement therapy.
- •Clinically not-controlled chronic or ongoing infectious disease requiring treatment at the time of study day 1 or within the 14 days before study day 1
- •Symptomatic peripheral sensory or motor neuropathy of grade ≥3
- •History or presence of clinically relevant central nervous system (CNS) pathology as uncontrolled epilepsy or seizure disorder, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, and psychosis
- •Active hepatitis B and C based on the following results: a) Positive for HepBsAg; b) Negative HepBsAg and positive for hepatitis B core antibody; c) Positive Hepatitis C virus antibody (HepCAb)
- •Known or suspected HIV infection or subjects who are HIV seropositive
- •Baseline ECG QTc > 470 msec (applying Fridericia correction)
- •Previously received an allogeneic stem cell transplant and the occurrence of 1 or more of the following: a) received the transplant within 6 months prior to study day 1; b) received immunosuppressive therapy within the last 3 months prior to study day 1; c) any active acute graft versus host disease (GvHD), grade 2 to 4, according to the Glucksberg criteria or active chronic GvHD requiring systemic treatment; d) any systemic therapy against GvHD within 2 weeks prior to start of investigational product treatment
- •Autologous stem cell transplantation < 90 days prior to study day 1
- •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 < 2 weeks prior to study day 1
- •Last treatment with a therapeutic antibody less than 4 weeks prior to study day 1
- •Systemic radiation therapy within 28 days prior to study day
- •Focal radiotherapy within 14 days prior to study day
- •Major surgery defined as surgery requiring general anesthesia with endotracheal intubation within 28 days prior to study day 1, unless discussed with and eligibility approved by Amgen medical monitor
- •Prior treatment with any drug that specifically targets BCMA on tumor cells (eg, other bi-specific antibody constructs, antibody drug conjugates, or CAR T-cells, except for subjects who were previously treated with AMG 420 in this study and who are candidates for second-course treatment
- •Treatment with medications known to cause QTc interval prolongation within the washout periods described in Section 12.10 unless approved by the Amgen medical monitor
- •Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.
- •History or evidence of any other clinically-significant disorder, condition, or disease (eg, symptomatic congestive heart failure, unstable angina pectoris,cardiac arrhythmia requiring therapy at time of screening) with the exception of those outlined above that, in the opinion of the investigator or Amgen medical monitor, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion.
研究组 & 干预措施
AMG 420
Single Arm Design
干预措施: AMG 420 (Drug)
结局指标
主要结局
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
时间窗: Up to approximately 3 years
The severity of TEAEs were graded using the CTCAE version 5.0 with the exception of CRS and TLS, which graded using the criteria referenced in the publication by Lee et al, 2014 and the Cairo Bishop criteria referenced in the publication by Coiffier et al, 2008. Any clinically significant changes in vital signs, electrocardiograms (ECGs) and clinical laboratory tests were recorded as TEAEs.
Number of Participants With Dose-limiting Toxicities (DLTs)
时间窗: Day 1 to Week 4
DLTs were graded using Common Terminology Criteria for Adverse Events (CTCAE) v5.0, with the exception of cytokine release syndrome (CRS) and tumor lysis syndrome (TLS), which graded using the criteria referenced in the publication by Lee et al, 2014 and the Cairo Bishop criteria referenced in the publication by Coiffier et al, 2008 respectively. A participant was non-DLT evaluable if they dropped out before completion of the DLT-evaluable period for reasons other than a DLT.
Number of Participants Who Experienced a Treatment-related TEAE
时间窗: Up to approximately 3 years
The severity of treatment-related TEAEs were graded using the CTCAE version 5.0 with the exception of CRS and TLS, which graded using the criteria referenced in the publication by Lee et al, 2014 and the Cairo Bishop criteria referenced in the publication by Coiffier et al, 2008. Treatment-related TEAEs were those that were considered related to the study treatment by the investigator.
次要结局
- Percentage of Participants With Minimal Residual Disease (MRD) Negativity Response at CR(Up to approximately 3 years)
- Duration of Response (DOR)(Up to approximately 3 years)
- Overall Response Rate (ORR)(Up to approximately 3 years)
- Number of Participants With Minimal Residual Disease (MRD) Negativity Response at CR(Up to approximately 3 years)