2024-510985-17-00
进行中（未招募）
2 期
A Phase 2, Open-Label, Randomized Study to Assess the Efficacy and Safety of Zolbetuximab (IMAB362) in Combination with Nab-Paclitaxel and Gemcitabine (Nab-P + GEM) as First Line Treatment in Subjects with Claudin 18.2 (CLDN18.2) Positive, Metastatic Pancreatic Adenocarcinoma
概览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 113
- 试验地点
- 44
- 主要终点
- ● Confirm RP2D as assessed by DLTs (Safety Lead-in Phase) ● Safety and tolerability as measured by AEs, laboratory test results, vital signs, ECGs and ECOG performance status. ● OS, defined as the time from the date of randomization until the date of death from any cause
概览
简要总结
- To confirm the recommended phase 2 dose (RP2D) of zolbetuximab in combination with Nab-P + GEM for subjects with CLDN18.2 positive, metastatic pancreatic adenocarcinoma (Safety Lead-in Phase);
- To assess whether treatment with zolbetuximab in combination with Nab-P + GEM improves overall survival (OS) compared to Nab-P + GEM in subjects with CLDN18.2 positive, metastatic pancreatic adenocarcinoma (Randomization Phase);
- To assess the safety and tolerability of zolbetuximab in combination with Nab-P + GEM.
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act Authorization for United States sites) must be obtained from the subject or legally authorized representative prior to any study related procedures (including withdrawal of prohibited medication, if applicable).
- •Subject has histologically or cytologically confirmed adenocarcinoma of pancreas.
- •Subjects must have metastatic pancreatic adenocarcinoma that has not been previously treated with chemotherapy. • Prior treatment with 5-FU or GEM administered as a radiation sensitizer during and up to 4 weeks after radiation therapy is allowed (if there is lingering toxicity, then the sponsor should be consulted). • If a subject received adjuvant therapy, tumor recurrence or disease progression must have occurred at least 6 months after completing the last dose of the adjuvant therapy. • Subjects whose disease progressed on prior treatment with Nab-P and GEM are not eligible.
- •Subject has a measurable lesion(s) on at least 1 metastatic site based on RECIST 1.1 within 28 days prior to randomization. For subjects with only 1 measureable lesion and prior radiotherapy, the lesion must be outside the field of prior radiotherapy or must have documented progression following radiation therapy.
- •Subject's tumor sample has CLDN18.2 expression in ≥ 75% of tumor cells demonstrating moderate to strong membranous staining as determined by central IHC testing. Physical or Laboratory Findings
- •Subject has ECOG performance status of 0 or 1
- •Subject has predicted life expectancy ≥ 12 weeks in the opinion of the investigator.
- •Subject must meet all of the following criteria based on the laboratory tests collected within 14 days prior to randomization. In case of multiple laboratory data within this period, the most recent data should be used. •Hemoglobin ≥ 9 g/dl (no transfusion within 14 days of start of study treatment) •Absolute neutrophil count ≥ 1.5 x 109 /L •Platelets ≥ 100 x 109 /L •Albumin ≥ 2.5 g/dL •Total bilirubin ≤ 1.5 x upper limit of normal (ULN) •Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN without liver metastases (≤ 5 x ULN if liver metastases are present) •Estimated creatinine clearance ≥ 30 mL/min •Prothrombin time/international normalized ratio and partial thromboplastin time ≤ 1.5 x ULN (except for subjects receiving anticoagulation therapy)
- •Subject is considered an adult according to local regulation at the time of signing informed consent.
- •Subject agrees not to participate in another interventional study while receiving study drug in present study.
排除标准
- •Subject has received other investigational treatment within 28 days prior to randomization.
- •Subject has active infection requiring systemic therapy that has not completely resolved per investigator judgment within 7 days prior to randomizatio
- •Subject has significant cardiovascular disease, including: ● Congestive heart failure (defined as New York Heart Association Class III or IV), myocardial infarction, unstable angina, coronary angioplasty, coronary stenting, coronary artery bypass graft, cerebrovascular accident or hypertensive crisis within 6 months prior to randomization; ● History of clinically significant ventricular arrhythmias (i.e., sustained ventricular tachycardia, ventricular fibrillation or Torsades de Pointes); ● QTc interval > 450 msec for male subjects; QTc interval > 470 msec for female subjects; ● Cardiac arrhythmias requiring anti-arrhythmic medications (Subjects with rate controlled atrial fibrillation for > 1 month prior to randomization are eligible.)
- •Subject has a history of central nervous system metastases and/or carcinomatous meningitis from pancreatic adenocarcinoma
- •Subject has known peripheral sensory neuropathy ≥ Grade 2 per CTCAE v.4.03 unless the absence of deep tendon reflexes is the sole neurological abnormality
- •Subject has had a major surgical procedure ≤ 28 days prior to randomization.
- •Subject without complete recovery from a major surgical procedure ≤ 14 days prior to randomization.
- •Psychiatric illness or social situations that would preclude study compliance per investigator's judgment.
- •Subject has another malignancy for which treatment is required per investigator's clinical judgment
- •Subject has any concurrent disease, infection or co-morbid condition that interferes with the ability of the subject to participate in the study, which places the subject at undue risk or complicates the interpretation of data in the opinion of the investigator.
结局指标
主要结局
● Confirm RP2D as assessed by DLTs (Safety Lead-in Phase) ● Safety and tolerability as measured by AEs, laboratory test results, vital signs, ECGs and ECOG performance status. ● OS, defined as the time from the date of randomization until the date of death from any cause
● Confirm RP2D as assessed by DLTs (Safety Lead-in Phase) ● Safety and tolerability as measured by AEs, laboratory test results, vital signs, ECGs and ECOG performance status. ● OS, defined as the time from the date of randomization until the date of death from any cause
次要结局
- ● PFS, defined as the time from the date of randomization until the date of radiological PD per RECIST 1.1 by local investigator evaluation, or death from any cause, whichever is earliest
- ● ORR, defined as the proportion of subjects who have a best overall response of CR or PR as assessed by local investigator evaluation per RECIST 1.1
- Pharmacokinetic parameters of zolbetuximab, Nab-P and GEM (AUCinf, AUCinf [%extrap], AUClast, Cmax, Ctrough, tmax, t1/2, tlast, CL, Vz, as appropriate
- DCR, defined as the proportion of subjects who have a best overall response of CR, PR or stable disease (SD) as assessed by local investigator evaluation per RECIST 1.1
- ● DOR, defined as the time from the date of the first response (CR/PR) until the date of PD as assessed by local investigator evaluation per RECIST 1.1 or date of death from any cause, whichever is earlies
- Time to worsening of pancreatic pain and GHS/QoL as measured by QLQ-C30, QLQ-PAN26, and PGIS as key HRQOL endpoints
- HRQoL, as collected viameasured by EORTC QLQ-C30, EORTC QLQPAN26 (including remaining domains besides pancreatic pain), EORTC QLQ-C30 (including remaining domains besides GHS/QoL), EQ-5D-5L, PGIS and PGIC questionnaires
- Serum CA19-9 change from baseline
- Immunogenicity of zolbetuximab as measured by the frequency of anti-drug antibody (ADA) positive subjects.
研究者
Head of Clinical Trial Unit Regulatory Affairs
Scientific
Astellas Pharma Global Development Inc.
研究点 (44)
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