A Phase 1/2 Multicenter, Open-label, Dose-escalation, and Dose-expansion Study to Evaluate the Safety, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI4276 in Subjects with Select HER2-expressing Advanced Solid Tumors

MedImmune LLC, a wholly owned subsidiary of AstraZeneca PLC0 个研究点目标入组 216 人开始时间: 2017年7月28日最近更新: 2018年6月11日

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方
入组人数: 216

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•1.Age = 18 years at the time of screening.
•2.Written informed consent and any locally required authorization obtained from the subject prior to performing any protocol related procedures, including screening evaluations.
•3.In the dose-escalation phase:
•a.Histologically or cytologically documented unresectable, locally advanced or metastatic breast or gastric cancer refractory to standard therapy.
•b.HER2-positive disease documented as FISH-positive and/or 3+ by IHC on previously collected tumor tissue.
•c.At least one lesion measurable by RECIST Version 1.1
•4.In the dose-expansion phase:
•a.Cohort 1 (T-DM1 progressors, HER2-positive breast cancer) must meet all of the following:
•i.Histologically or cytologically documented unresectable, locally advanced or metastatic breast cancer (locally advanced disease must not be amenable to surgical resection or radiation with curative intent).
•ii.At least one lesion measurable by RECIST Version 1.1. NOTE: A previously irradiated lesion can be considered a target lesion if the lesion is well defined, measurable per RECIST v1.1, there is objective evidence for interval increase in size, and the subject consents to providing the prior computed tomography (CT) scan before enrolling in the study.
•iii.HER2-positive disease documented as FISH-positive and/or 3+ by IHC based on previously collected tumor tissue.
•iv.Subjects with a primary tumor that is hormone (estrogen, progesterone, or both) receptor positive or receptor-negative are eligible
•v.Prior treatment with trastuzumab + pertuzumab-based regimen
•vi.Prior treatment with T-DM1 in the metastatic setting with documented radiographic disease progression while receiving or after completing T-DM1.
•vii.Prior hormone therapy is allowed, but last dose must be at least 14 days prior to first dose of MEDI4276
•viii.Documented radiographic disease progression during or after the most recent treatment is also required if not T-DM1.
•b.Cohort 2 (TNBC) must meet all of the following:
•i.Histologically or cytologically documented unresectable, locally advanced or metastatic breast cancer (locally advanced disease must not be amenable to either surgical resection or radiation with curative intent).
•ii.At least one lesion measurable by RECIST Version 1.1. NOTE: A previously irradiated lesion can be considered a target lesion if the lesion is well defined, measurable per RECIST v1.1, there is objective evidence for interval increase in size, and the subject consents to providing the prior CT scan before enrolling in the study.
•iii.HER2-negative disease documented according to 2013 ASCO/College of American Pathologists (CAP) HER2 Testing Clinical Practice Guidelines (Wolff et al, 2013) as HER2 0, 1+ by IHC or HER2 2+ by IHC on previously collected tumor tissue. If HER2 2+ by IHC is documented, FISH must also be performed and the ratio of HER2 to chromosome enumeration probe 17 (CEP17) must be < 2.0 or average HER2 gene copy number must be < 4 signals per nucleus.
•iv.ER/PR-negative documented disease according to 2010 ASCO/CAP Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer (Hammond et al, 2010), defined as < 1% of tumor cell nuclei are immunoreactive by IHC.
•v.If futility criteria are met in the TNBC all-comers population after an initial 15 subjects are enrolled and evaluated, then further enrollment will be limited to the TNBC HER2Low population defined as the subset of TNBC subjects with tumor

排除标准

•1.Receipt of any conventional or investigational anticancer treatment within 28 days prior to the first dose of MEDI4276.
•2.History of exposure to the following cumulative doses of anthracyclines:
•a.Doxorubicin or liposomal doxorubicin > 350 mg/m2.
•b.Epirubicin > 530 mg/m2.
•c.Mitoxantrone > 90 mg/m2 and idarubicin > 70 mg/m2.
•d.If another anthracycline or more than 1 anthracycline has been used, then the cumulative dose must not exceed the equivalent of 350 mg/m2 of doxorubicin.
•3.Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v4.03 Grade 0 or 1 with the exception of Grade 2 peripheral neuropathy that is clinically stable for at least 28 days prior to the first dose of MEDI4276, alopecia, and laboratory values listed per the inclusion criteria. NOTE: Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (eg, hearing loss) after consultation with the medical monitor.
•4.Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study.
•5.History of or currently with symptomatic congestive heart failure (New York Heart Association classes II-IV) or serious cardiac arrhythmia requiring treatment.
•6.Cardiac troponin I = 0.2 ng/mL within 28 days prior to the first dose of MEDI4276.
•7.History of myocardial infarction or unstable angina within 6 months of the first dose of MEDI4276.
•8.History of intolerance (such as Grade 3 or Grade 4 infusion-related reaction) to trastuzumab or T-DM1.
•9.Known hypersensitivity to any component of MEDI4276, including the excipients.
•10.Any of the following within 6 months before the first dose of MEDI4276: active peptic ulcer disease, active inflammatory bowel disease (including ulcerative colitis and Crohn’s disease).
•11.Diarrhea of any grade within 14 days prior to the first dose of MEDI4276.
•12.Previous radiotherapy is not allowed if:
•a.More than 25% of marrow-bearing bone has been irradiated.
•b.The last fraction of radiotherapy has been administered within approximately 3 weeks prior to the first dose of MEDI4276.
•13.Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms; or any radiation, surgery, or other therapy to control symptoms from brain metastases within 2 months prior to first dose of MEDI4276.
•?CT or magnetic resonance imaging (MRI) scan of the brain is mandatory (within approximately 28 days prior to first dose of MEDI4276) in cases of clinical suspicion of brain metastases or in a patient with any prior history of brain metastases.
•14.Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs from MEDI4276, or compromise the ability of the subject to give written informed consent.
•15.Current severe, uncontrolled systemic disease (eg, clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures).
•16.Major surgical procedure or significant traumatic injury (as defined by the investigator) within approximately 28 days prior to first dose of MEDI4276 or anticipation of the need for major surgery during the course of study treatment.
•17.Current pregnancy or lactation.

研究者

发起方

MedImmune LLC, a wholly owned subsidiary of AstraZeneca PLC

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