An Open-label Phase 1b/2 Study Assessing the Safety and Efficacy of Mitazalimab in Combination With Chemotherapy in Patients With Metastatic Pancreatic Ductal Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 94
- 试验地点
- 14
- 主要终点
- Incidence of Dose Limiting Toxicities (DLTs) (Part 1: Phase 1b Dose escalation)
研究概览
简要总结
Phase 1b/2 study to assess the safety and efficacy of mitazalimab in combination with chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma.
详细描述
OPTIMIZE-1 is a phase 1b/2, open-label, multi-center study assessing the clinical efficacy of mitazalimab in combination with chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma.
The efficacy of intravenously administered mitazalimab in combination with the standard of care chemotherapy mFOLFIRINOX will be evaluated in patients with metastatic pancreatic ductal adenocarcinoma. Two dose levels of mitazalimab, 450 ug/kg and 900 ug/kg, are planned to be evaluated together with mFOLFIRINOX for determination of recommended phase 2 dose (RP2D) of mitazalimab in combination with mFOLFIRINOX before entering a dose expansion part with RP2D obtained. The expansion part will evaluate the clinical efficacy of mitazalimab in combination with mFOLFIRINOX assessing objective response rate (ORR), primary endpoint, as well as Progression-free survival (PFS) and Overall survival (OS). The dose expansion part includes a Simon´s two-stage design with an interim analysis for stop for futility or efficacy based on ORR.
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
- •Has provided written informed consent
- •Is ≥18 years of age at the time of signing the informed consent form (ICF)
- •Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Has a diagnosis of previously untreated metastatic pancreatic ductal adenocarcinoma (histologically documented)
- •Has measurable disease per RECIST v. 1.1
- •Has not received previous chemotherapy for pancreatic ductal adenocarcinoma
- •Has not received prior abdominal radiotherapy (except for palliative radiotherapy to non-target lesions)
- •Has a life expectancy of ≥ 3 months
- •Has acceptable hematologic laboratory values defined as:
- •Neutrophils ≥ 1.5 x 109/L without growth factor stimulation within 3 weeks prior to the blood test
- •Platelets ≥100 x 109/L
- •Hemoglobin ≥6.2 mmol/L (~100 g/L) (may be after transfusion)
- •Has acceptable clinical chemistry laboratory values defined as:
- •Bilirubin ≤1.5 x ULN (biliary drainage is permitted)
- •AST ≤3 x ULN (irrespective of hepatic metastases)
- •ALT ≤3 x ULN (irrespective of hepatic metastases)
- •Creatinine ≤1.5 x ULN or glomerular filtration rate (GFR) of ≥45 mL/min
- •INR ≤1.5 x ULN
- •Albumin ≥28 g/L
- •For women of childbearing potential1:
- •Has a negative highly sensitive serum (β-human chorionic gonadotropin [β-hCG]) pregnancy test at screening
- •Is willing to use highly effective contraception methods during study treatment and for at least six months thereafter
- •Fertile men must practice effective contraceptive methods (i.e. surgical sterilization, or a condom used with a spermicide) during study treatment and for at least six months thereafter
- •Is willing to comply with all study procedures
排除标准
- •Has other types of non-ductal tumor of the pancreas, including endocrine tumors or acinar cell adenocarcinoma, cyst adenocarcinoma and ampullary carcinoma
- •Has other current cancer or history of cancer in the prior 3 years before signing the ICF other than in situ cervical cancer, or basal cell or squamous cell carcinoma treated with local excision only
- •Has known CNS metastases or carcinomatous meningitis
- •Has contraindication to any constituent of study treatment (mitazalimab and applicable chemotherapy)
- •Has a history of chronic diarrhea, inflammatory disease of the colon or rectum, or unresolved partial or complete intestinal obstruction
- •Has a history of myocardial infarction within 12 months of the first administration of mitazalimab, uncontrolled angina pectoris, unstable cardiac arrhythmias, or congestive heart failure of New York Heart Association class II or greater
- •Has QTc >450 msec
- •Has uncontrolled intercurrent illness, including active infection
- •Has a known history of HIV, hepatitis B or active hepatitis C infection
- •Is a female patient who is pregnant or nursing
- •Has received attenuated vaccine within 28 days before the first dose of study treatment
- •Any condition that, in the opinion of the Investigator, would place the patient at increased risk or preclude the patient's compliance with the study
- •Participates in another investigational drug or device study with any intervention within the previous 4 weeks prior to first dose of mitazalimab
- •Has received prior treatment with irinotecan or platinum-containing chemotherapy
- •Has pre-existing peripheral neuropathy greater than grade 1
- •Has known Gilbert's disease
- •Has known genotype UGT1A1 * 28 / * 28
- •Has known fructose intolerance (malabsorption)
- •Has complete dihydropyrimidine dehydrogenase (DPD) deficiency
研究组 & 干预措施
Intravenously administered mitazalimab given in combination with chemotherapy
Mitazalimab, a human monoclonal antibody targeting CD40, administered intravenously every 14 days, in combination with standard of care chemotherapy modified FOLFIRINOX.
干预措施: CD40 agonist mitazalimab in combination with chemotherapy (Biological)
结局指标
主要结局
Incidence of Dose Limiting Toxicities (DLTs) (Part 1: Phase 1b Dose escalation)
时间窗: From first dose to end of dose limiting toxicity period (Day 1-21)
Number of patients experiencing DLTs
Objective response rate (ORR) (Part 2: Phase 2 Dose expansion)
时间窗: From first dose to 28-56 days after end of study treatment
Proportion of patients achieving complete response or partial response at any time during the study
次要结局
- Progression free survival (efficacy)(From first dose and up to 2 years after end of study treatment)
- Type, frequency and severity of Adverse Events(From informed consent signed to 28-56 days after end of of study treatment)
- Anti-drug-antibody (ADA) titer in serum (tolerability)(From first dose until 28-56 days after end of study treatment)
- Cmax of mitazalimab (pharmacokinetics)(From first dose until 28-56 days after end of study treatment)
- Anti-tumor Activity per RECIST 1.1 guideline (efficacy)(From first dose until 28-56 days after end of study treatment)
- Tmax of mitazalimab (pharmacokinetics)(From first dose until 28-56 days after end of study treatment)
- Overall survival (efficacy)(From first dose and up to 2 years after end of study treatment)
- AUC(0-T) of mitazalimab (pharmacokinetics)(From first dose until 28-56 days after end of study treatment)