A First-in-human Phase 1a/1b Study to Evaluate Safety and Tolerability of QXL138AM in Patients With Locally Advanced Un-resectable and/or Metastatic Solid Tumors and Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 16
- 主要终点
- Incidence of Adverse Events
研究概览
简要总结
Study QXL138AM-001 is a Phase 1a/1b study to investigate the safety, pharmacokinetics, and preliminary activity of QXL138AM in subjects with locally advanced un-resectable and/or metastatic solid tumors and multiple myeloma. The study is an open-label, multicenter, first in human study to be conducted in two major parts which are further organized into two sub-parts. Part A Dose Escalation is a modified 3+3 with the first two cohorts consisting of one subject each based on the low clinical starting dose. Dose escalation in solid tumors (Part A1) will be followed by dose finding in multiple myeloma (Part A2). Part B consists of dose expansion in solid tumors (Part B1) and multiple myeloma (Part B2) using the recommended dose for expansion from Part A
详细描述
This is an open-label, multicenter, first in human (FIH) Phase 1a/1b study of QXL138AM in participants with locally advanced unresectable and/or metastatic solid tumors and multiple myeloma. This study will be conducted in two parts (A and B) and each part has two sub-parts for tumor type (1 and 2).
Part A1 - Dose Escalation in Solid Tumors The following solid tumor types will initially be enrolled in this part: ovarian, pancreatic, urothelial, renal, hepatocellular, gastrointestinal, lung, prostate, and breast cancer.
Dose escalation will use a standard 3+3 design, where 3 to 6 participants with advanced solid tumors will be enrolled sequentially into each cohort/dose level with the exception of Cohort 1 and 2. For Cohorts 1 and 2, given the very low starting dose, only one participant is planned for each level unless a participant experiences a Grade 2 or higher adverse event not clearly and incontrovertibly related to disease progression or an extraneous factor. If such a Grade 2 or higher event occurs in Cohort 1 or 2, dose escalation will switch to a standard 3+3 design. Dose escalation will continue until the MTD or RDE is determined in participants with solid tumors, referred to as the RDE-ST. At this point, the two solid tumor types for dose expansion will be selected for Part B1 and may begin at the RDE-ST.
The proposed dose levels are defined in the table below. Cohort No. of Participants Dose Level (Q2W) (mg/kg)
- 1-6 0.001
- 1-6 0.003
- 3-6 0.01
- 3-6 0.03
- 3-6 0.1
- 3-6 0.3
- 3-6 1
- 3-6 2
- 3-6 4 Infusions will be administered via syringe pump or IV bag (depending on the dose) and administered over a 30-60-minute (± 10 minutes) duration.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open-label
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 with Solid Tumors
- •Histopathologically confirmed diagnosis of an advanced, unresectable, or metastatic solid tumor (ovarian, pancreatic, urothelial, renal, hepatocellular, gastrointestinal (GI), lung, prostate, and breast cancer).
- •Have progressed despite standard therapies, or for whom conventional therapy is not effective or tolerable, as judged by the Investigator. Patients must have no available therapeutic options known to confer clinical benefit for their tumor type.
- •Participants with Multiple Myeloma
- •Have progressed despite standard therapies, or for whom conventional therapy is not effective or tolerable, as judged by the Investigator.
- •Patients must have failed at least 3 prior therapies for myeloma and should have had prior exposure to a proteosome inhibitor, an IMiD, and an anti-CD38-directed therapy.
- •2. Male or female participants ≥18 years of age at the time of informed consent
- •An Eastern Cooperative Oncology Group (ECOG) performance status scale of 0, 1, or 2 at Screening
- •Must have at least 1 measurable lesion by RECIST version 1.1 (solid tumors only), or evaluable disease by IMWG Uniform Response Criteria (multiple myeloma only)
- •Adequate organ function and bone marrow reserve
- •Adequate cardiac function as estimated by left ventricular ejection fraction
- •Female participants of child-bearing potential must:
- •Have a negative serum pregnancy test at screening and a negative pregnancy test at Week 1 Day 1 prior to first dose of QXL138AM, AND
- •Agree to use at least 1 highly effective method of contraception for the duration of study participation, and for 120 days after last dose of QXL138AM.
- •8. Male participants of child-bearing potential must:
- •Agree to use at least 1 highly effective method of contraception for the duration of study participation, and for 120 days after last dose of QXL138AM, AND
- •Refrain from sperm donation prior to the first dose of investigational product through 120 days following the last dose of QXL138AM.
排除标准
- •New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, a history of risk factors for Torsades de Pointes (TdP), including heart failure, hypokalemia, and family history of long QTc syndrome, or evidence of ischemia on ECG.
- •Symptomatic ischemic heart disease or unstable angina pectoris; or history of cardiac angioplasty, cardiac stenting, or coronary artery bypass graft. A clinically significant baseline prolongation of QT/QTcF interval at screening.
- •The use of concomitant medications that may significantly prolong the QT/QTc interval.
- •Active, uncontrolled bacterial, viral, or fungal infections requiring systemic therapy.
- •Known hypersensitivity to the investigational product or components (anti-CD138 IgG1 antibody, Interferon A2a and/or the formulation excipients: histidine, sucrose, arginine, polysorbate 80).
- •Female participant is lactating.
- •Any other clinically significant comorbidities.
- •Received prior anticancer therapy within 28 days or 5x the half-life (whichever is shorter) prior to the first dose of investigational product.
- •Participants who received wide-field radiation therapy within 4 weeks prior to first dose of investigational product, (2 weeks for limited field radiation therapy)
- •Major surgery within 30 days before first dose of investigational product
- •Chronic use of systemic corticosteroids of more than 20 mg/day of prednisone or equivalent.
- •Active, clinically significant liver disease such as Hepatitis B or C, autoimmune hepatitis, or cirrhosis (Child Hugh Stage B or C).
- •Current or history of mood disorder such as major depression per DSM-5 within past two years not controlled with current therapy.
- •Active autoimmune disorders not controlled with current therapy.
- •Active endocrine disorders including hypothyroidism, hyperthyroidism, hypoglycemia, hyperglycemia, and diabetes mellitus not controlled with current therapy.
研究组 & 干预措施
Phase 1a Dose Escalation in Solid Tumors - Part A1
Dose escalation of QXL138AM in participants with locally advanced un-resectable and/or metastatic solid tumors.
干预措施: QXL138AM Injection every 2 weeks by IV Infusion (Biological)
Phase 1a Dose Escalation in Multiple Myeloma - Part A2
Dose escalation of QXL138AM in participants with multiple myeloma.
干预措施: QXL138AM Injection every 2 weeks by IV Infusion (Biological)
Phase 1b Dose Expansion in Solid Tumors - Part B1
Dose expansion in solid tumors using the recommended dose for expansion from Part A1
干预措施: QXL138AM Injection every 2 weeks by IV Infusion (Biological)
Phase 1b Dose Expansion in Multiple Myeloma - Part B2
Dose expansion in Multiple Myeloma using the recommended dose for expansion from Part A2
干预措施: QXL138AM Injection every 2 weeks by IV Infusion (Biological)
结局指标
主要结局
Incidence of Adverse Events
时间窗: Throughout study - anticipated 3.5 years
Record all safety events during study including AEs, SAEs, DLTs, AESIs.
次要结局
- Measurement of maximum plasma concentration (Cmax) of QXL138AM(Throughout study - anticipated 3.5 years)
- Measurement of area under the serum concentration-time curve (AUC) of QXL138AM(Throughout study - anticipated 3.5 years)
- Describe Anti-tumor activity(Part B of study - anticipated 1.5 years)
- Measurement of trough concentration (Ctrough) of QXL138AM(Throughout study - anticipated 3.5 years)
- Incidence of Anti-drug Antibodies(Throughout study - anticipated 3.5 years)