A Phase 1, Open-Label, Dose-Escalation, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of MT-0169 in Patients With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 14
- 试验地点
- 7
- 主要终点
- Maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)
研究概览
简要总结
This will be a Phase 1 Open-Label, dose escalation of MT-0169 (an Engineered toxin body (ETB) in patients with relapsed or refractory multiple myeloma. MT-0169 is an investigational drug that recognizes and binds to the CD38 receptor, which may be found on the surface of multiple myeloma cancer cells. It delivers a dose of a modified toxin that kills these cells.
详细描述
The drug being tested in this study is called MT-0169. The study will evaluate the safety, tolerability, preliminary efficacy, PK, pharmacodynamics, and immunogenicity of MT-0169 monotherapy in participants with RRMM.
The study will enroll up to 54 total participants.
The purpose of this study is to evaluate the safety and tolerability of MT-0169 in subjects with relapsed or refractory multiple myeloma (RRMM) and to estimate the maximum tolerated dose (MTD) or the recommended Phase 2 dose (RP2D).
MT-0169 will be given as an intravenous (IV) infusion over 60 minutes on the same day every week (i.e., days 1, 8, 15 and 22) or every 2 weeks (i.e., days 1 and 15) of each cycle. A cycle is defined as 28 days.
A subject may participate for the following three (3) periods:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Other
- 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
- 未提供
排除标准
- •With polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, amyloidosis, Waldenström macroglobulinemia, or Immunoglobulin M (IgM) myeloma.
- •With sensory or motor neuropathy of NCI CTCAE V5 Grade ≥
- •Have received final dose of any of the following treatments/procedures within the following interval before the first dose of MT-0169:
- •Myeloma-specific therapy, including PIs and IMiDs: 14 days
- •Anti-CD38 (a) therapy: Isatuximab 90 days; daratumumab 60 days
- •Corticosteroid therapy for myeloma: 7 days
- •Radiation therapy for localized bone lesions: 14 days
- •Major surgery:30 days
- •Autologous stem cell transplant: 90 days
- •Investigational therapy: 30 days
- •Have received an allogeneic stem cell transplant or organ transplantation.
- •Have not recovered to Grade ≤1 or baseline, from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) excluding alopecia and Grade 2 neuropathy.
- •With clinical signs of central nervous system (CNS) involvement of MM.
- •With a history of myelodysplastic syndrome or another malignancy other than MM except for the following: any malignancy in complete remission for 3 years, adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, or asymptomatic prostate cancer without known metastatic disease and not requiring therapy or requiring only hormonal therapy and with normal prostate-specific antigen level for ≥1 year before the start of study therapy.
- •With known or suspected light chain amyloidosis of any organ (amyloid on the BM biopsy without other evidence of amyloidosis is acceptable).
- •With any of the following cardiovascular conditions:
- •Congestive heart failure (NYHA) class ≥II or cardiomyopathy, active ischemia, or any other uncontrolled cardiac condition or myocardial infarction or clinically significant arrhythmia requiring therapy including anticoagulants within the past 6 months or at screening (stable therapy for > 6 months is acceptable).
- •Resting tachycardia (heart rate of > 100 bpm) at screening
- •Clinically significant uncontrolled hypertension at screening
- •Cardiac MRI at screening demonstrates evidence of amyloid cardiomyopathy or myocarditis
- •With a history of documented significant pleural or pericardial effusions of at least CTCAE Grade 3 within 3 months before the start of treatment. This will also exclude patients with:
- •Pericarditis (any Grade)
- •Non-malignant pleural effusion (Grade ≥2)
- •Patients with a history of noncardiogenic pulmonary edema associated with diffuse peripheral edema and history of intravascular hypovolemia associated with systemic antineoplastic therapy.
- •With chronic or active infection requiring systemic therapy, history of symptomatic viral infection that has not been fully cured. The following exceptions apply for those with positive serologies of HIV, HBV, or HCV:
- •With HIV and an undetectable viral load and CD4+ T-cell (CD4+) counts ≥350 cells/mL may be allowed but patient must be taking appropriate opportunistic infection prophylaxis if clinically relevant
- •With positive HBV serology may be allowed if undetectable viral load, receiving antiviral prophylaxis for potential HBV reactivation per institutional guidelines
- •With positive HCV serology may be allowed if quantitative PCR for plasma HCV RNA is below the lower limit of detection. Concurrent antiviral HCV treatment per institutional guidelines is allowed.
- •Have received a live attenuated vaccine within 28 days of first dose of MT-
- •With a history of CTCAE Grade 3 ≥ systemic inflammatory response syndrome (SIRS)/ cytokine release syndrome (CRS) reactions following infusion with any monoclonal antibodies (mAbs) or Chimeric Antigen Receptor (CAR) T therapy
- •With a chronic condition requiring systemic corticosteroids at >10 mg/day of prednisone or equivalent.
- •Are lactating and breastfeeding or have a positive serum pregnancy test during the screening period or patients of reproductive potential who are not employing an effective birth control
- •With a concurrent medical or psychiatric illness that would preclude study conduct and assessment including, but not limited to, uncontrolled medical conditions, active infection, risk of bleeding, diabetes mellitus, pulmonary disease, alcoholic liver disease, or primary biliary cirrhosis.
- •With known allergy or intolerance to any of the drugs used in the study or excipients in MT-0169
- •With a history of hypersensitivity or serious toxic reaction to kanamycin or another aminoglycoside.
- •Failed to recover to Grade ≤1 or baseline from adverse reactions to prior treatment or procedures (chemotherapy, immunotherapy, radiation therapy) excluding alopecia and stable Grade 2 neuropathy.
研究组 & 干预措施
Part 1: Dose Escalation
Weekly Dosing Intravenous (IV) infusion of MT-0169 every 7 days: Days 1, 8, 15, and 22 in a 28-day treatment cycle.
Every 2 Weeks IV infusion of MT-0169 every 14 days: Days 1 and 15 in a 28-day treatment cycle with escalating doses starting at the MTD/RP2D determined by the weekly dose escalation cohort.
Patients will continue to receive treatment until progressive disease, unacceptable toxicity or withdraw from the study for other reasons. Decision to escalate/deescalate/stay on the same dose/discontinue MT-0169 will be based on number of DLTs per number of patients enrolled at each dose level as predetermined by the mTPI-2 statistical model. Subsequent doses will be determined by the frequency and severity of adverse events in previous cohorts. The investigator and sponsor review of available safety, PK, pharmacodynamics, and efficacy data in the previous cohorts will also be factored in the decision.
干预措施: MT-0169 (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D)
时间窗: Up to 12 months
Number of participants with Grade greater than or equal to (>=) 3 TEAEs according to NCI CTCAE 5.0
时间窗: Up to 12 months
Number of participants with Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to 12 months
Number of participants with Dose-limiting Toxicities (DLTs)
时间窗: Up to 12 months
Number of participants with Serious Adverse Events (SAEs)
时间窗: Up to 12 months
Number of participants who discontinued MT-0169 due to TEAEs
时间窗: Up to 12 months
Number of participants with treatment-related dose modifications
时间窗: Up to 12 months
Dose modifications include dose delays, dose interruptions, and dose reductions
次要结局
- Overall response rate (ORR)(Up to 12 months)
- Proportion of RRMM participants who achieved MR (minimal response)(Up to 12 months)
- AUClast: Area Under the Concentration-time Curve From Time 0 to the time of the last quantifiable concentration for MT-0169(Cycles 1 and 2, Day 1: pre-dose, and at multiple time points (up to 168 hours) post-dose (each cycle is 28 days))
- Clinical Benefit Rate (CBR) for RRMM patients(Up to 12 months)
- Progression-free Survival (PFS) for RRMM patients(From the date of first dose until the date of progressive disease (PD))
- Duration of Response (DOR)(Date of the dose administration until death due to any cause (up to 12 months))
- Time to Response (TTR)(From the date of the first dose of the study treatment to the date of the first documentation of response (up to 12 months))
- Cmax: maximum observed concentration for MT-0169(Cycles 1 and 2, Day 1: pre-dose, and at multiple time points (up to 168 hours) post-dose (each cycle is 28 days))
- Tmax: time to reach maximum observed concentration for MT-0169(Cycles 1 and 2, Day 1: pre-dose, and at multiple time points (up to 168 hours) post-dose (each cycle is 28 days))
- Number of participants with Anti-drug Antibodies following administration of MT-0169(Up to 12 months)
- Percentage of participants with RRMM who achieved Complete Response (CR) or Very Good Partial Response (VGPR)(Up to 12 months)
- Overall survival (OS)(From date of the dose administration until death due to any cause (up to 12 months))