EUCTR2012-002206-52-GB进行中（未招募）1 期
A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MEDI4736 in Subjects with Advanced Solid Tumors
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- MedImmune
- 入组人数
- 1,322
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
- •Written informed consent.
- •Dose-escalation phase: histologically-or cytologically- confirmed
- •advanced melanoma, renal cell carcinoma, non-small cell lung cancer, or colorectal cancer that is refractory to standard therapy and for which no standard therapy exists.
- •Dose-expansion phase: histologically-or cytologically-confirmed
- •advanced utaneous melanoma, uveal melanoma, HCC, SCCHN, NSCLC squamous and non-squamous, gastroesophageal cancer, TNBC, or pancreatic adenocarcinoma, urothelial bladder cancer, GBM, epithelial ovarian cancer, soft tissue sarcoma, SCLC, MSI-high cancers, HPV-positive cancers, or nasopharyngeal carcinoma.
- •HCC subjects must be of Child-Pugh class A (not amenable to or
- •refractory to locoregional therapy). Subjects with HCC associated with hepatitis B virus must be receiving adequate antiviral therapy.
- •Subjects with histologically or cytologically confirmed inoperable or metastatic transitional cell carcinoma of the urothelium (subjects must have received and have progressed or are refractory to at least 1 but not more than 2 prior lines of systemic therapy for inoperable or metastatic disease)
- •Subjects with histologically or cytologically documented NSCLC must
- •present with Stage IIIB/ Stage IV disease, or with recurrent or progressive disease following multimodal therapy for locally advanced disease (refer to protocol for further details).
- •Subjects with SCCHN must have disease that is either metastatic or
- •recurrent and deemed to be incurable by the investigator.
- •MSI-high cancers must have defective DNA mismatch repair by EITHER high-frequency microsatellite instability with changes detected in 2 or more panels of microsatellite markers (BAT-25, BAT-26, NR-21, NR-24 and MONO-27) OR immunohistochemical analysis demonstrating
- •absence of protein expression of any 1 or more of the following proteins: MLH1, MSH2, MSH6, PMS2.
- •Subjects with HPV-positive cancers are eligible if they have a confirmed HPV positive tumor by local laboratory.
- •GBM cohort: Subjects with GBM must not have significant edema or shift from midline by intracranial imaging, or be symptomatic due to edema. A minimum of 10 subjects without O6-methylguanine-DNA
- •methyltransferase promoter methylation will be enrolled in the GBM
- •Epithelial ovarian cancer cohort: A minimum of 10 subjects with
- •platinum sensitivity will be enrolled in the ovarian cancer cohort
- •If an approved first-line standard therapy is available, subjects must have failed, be intolerant to, be ineligible for, or have refused treatment.
- •Progressive disease as assessed by the investigator or treatment naïve at the time of study entry.
- •Tumoral PD-L1 expression requirements are as follows:
- •·HCC, gastroesophageal cancer, TNBC, GBM, ovarian cancer, soft tissue sarcoma, SCLC, HPV-positive cancers, pancreatic adenocarcinoma, and nasopharyngeal carcinoma dose-expansion cohorts: after the first 20-40 subjects in each cohort are enrolled, additional subjects in the applicable cohorts may be required to have tumoral PD-L1 expression as determined by prospective testing prior to enrollment.
- •NSCLC (squamous and non-squamous) dose-expansion cohorts:
- •Non-squamous NSCLC: all remaining subjects to be enrolled will be required to have tumoural PD-L1 expression as determined by prospective testing prior to enrollement.
- •Squamous NSCLC: a minimum of 10 subjects in the first-line therapy cohort, and a minimum of 35 subjects in each of the second-line therapy and third-line or greater
排除标准
- •Concurrent enrollment in another clinical study, unless it is an
- •observational (non-interventional) clinical study or the follow-up period of an interventional study.
- •Receipt of any immunotherapy, BRAF inhibitor (in cutaneous melanoma and uveal melanoma subjects), or investigational anticancer therapy within 4 weeks prior to the first dose of MEDI4736; in the case of MAbs, 6 weeks prior to the first dose of
- •Any prior Grade = 3 irAE while receiving immunotherapy.
- •For all subjects: prior exposure to any anti-PD-1 or anti-PD-L1 antibody.
- •For UBC cohort: prior treatment with immunotherapy agents including, but not limited to, tumor necrosis factor receptor superfamily agonists or checkpoint inhibitors or natural killer (NK) cell inhibitors including agents targeting KIR, PD-1, PD-L1, CTLA-4, OX40, CD27, CD137 (4-1BB), CD357 (GITR), and CD40. Prior treatment with Bacillus Calmette-Guerin therapy is permitted.
- •Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment.
- •Current or prior use of immunosuppressive medication within 28 days before the first dose of MEDI4736.
- •Active or prior documented autoimmune disease within the past 2 years
- •NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
- •Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
- •History of primary immunodeficiency.
- •History of organ transplant that requires use of immunosuppressives.
- •Known allergy or reaction to any component of the MEDI4736
- •formulation.
- •Untreated CNS metastatic disease, leptomeningeal disease, or cord
- •compression.
- •Other invasive malignancy within 2 years except for noninvasive
- •malignancies that have been surgically cured.
- •Unresolved toxicities from prior anticancer therapy.
- •Major surgical procedure (as defined by the investigator) within 30 days prior to the first dose of MEDI4736 or still recovering from prior surgery.
- •Females who are pregnant or lactating.
- •Uncontrolled intercurrent illness.
- •Any condition that would interfere with evaluation of the investigational product or interpretation of subject safety or study results.
- •Known history of tuberculosis.
- •Known to be human immunodeficiency virus (HIV) positive.
- •Hepatitis B or C infection.
- •Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving MEDI4736.
- •Subjects with pancreatic adenocarcinoma must not have more than 50% of the liver parenchyma replaced by tumour.
- •Subjects with HCC must not have a history of bleeding from esophageal varices, unless the varices have been treated with no active bleeding within 30 days prior to the first dose of MEDI4736.
- •Prior participation in clinical studies that include MEDI4736 alone or in combination, where the study has registrational intent and the analyses for the primary endpoint have not yet been completed.
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