EUCTR2019-004605-27-PL进行中（未招募）1 期
A Phase 1b/2 Dose Escalation/Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of GS-4224 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）
- 入组人数
- 18
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
- •Subjects must meet all of the following inclusion criteria to be eligible for participation in this study. Additional indication-specific inclusion criteria for 1000 mg BID Dose Escalation Cohort and Phase 2 are provided in Appendix 3.
- •1.Male or female = 18 years of age.
- •2.Dose Escalation Cohorts: Histologically or cytologically confirmed advanced malignant solid tumor that is refractory to or intolerant of all standard therapy or for which no standard therapy is available.
- •3.Dose Expansion and 1000 mg BID Dose Escalation Cohorts: Subjects must have available sufficient and adequate formalin fixed tumor sample preferably from a biopsy of a tumor lesion obtained either at the time of or after the diagnosis of advanced disease has been made and from a site not previously irradiated. Alternatively, subjects must agree to have a biopsy taken prior to entering the study to provide adequate tissue.
- •For the 1000 mg BID dose escalation cohort, subjects with melanoma, Merkel cell, MSI-H cancers, and cHL are not required to have archival or fresh biopsy tissue.
- •4.Dose Escalation Biopsy Substudy and 1000 mg BID Dose Escalation Cohorts: Documented PD-L1 expression in the tumor (TPS =10% or CPS = 10). See Appendix 3 for the PD-L1 expression requirement for specific tumor types.
- •a) In the 1000 mg BID cohort, PD-L1 expression will not be required for Merkel cell, melanoma, MSI-H cancers, and cHL.
- •5.All persisting toxic effects of any prior antitumor therapy resolved to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 Grade = 1 or baseline before the first dose of study drug (with the exception of alopecia [Grade 1 or 2 permitted] and neurotoxicity [Grade 1 or 2 permitted]).
- •6.Eastern Cooperative Oncology Group (ECOG) Performance Status of = 2.
- •7.Life expectancy of = 3 months, in the opinion of the investigator.
- •8.Adequate organ function defined as follows:
- •a)Hematologic: Platelets = 100 ? 109/L ( =60? 109/L in subjects with HCC); Hemoglobin = 9.0 g/dL; ANC = 1.5 ? 109/L (with without blood transfusion, platelet transfusion, or growth factors within previous 7 days of the hematologic laboratory values obtained at screening visit).
- •b)Hepatic: AST / ALT = 2.5 ? upper limit of normal (ULN) (if liver metastases are present, = 5 ? ULN); Total or conjugated bilirubin = 1.5 ? ULN.
- •c)Renal: Creatinine clearance (CLcr) = 45 mL/min as calculated by the Cockcroft Gault method.
- •9.Coagulation: Subjects on full-dose oral anticoagulation, except warfarin, which is an excluded medication, must be on a stable dose (minimum duration 14 days). Subjects on low molecular weight heparin will be allowed.
- •10.Negative serum pregnancy test for female subjects.
- •11.Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in Appendix 5.
- •12.Females who are nursing must agree to discontinue nursing before the first dose of GS-4224.
- •13.Able and willing to provide written informed consent to participate in the study.
- •14.Patients with history of human immunodeficiency virus (HIV) infection should have a CD4+ T-cell count = 350 cells/µL at screening.
- •15.Patients with serological evidence of chronic hepatitis B virus infection (HBV) should have HBV viral load below the limit of quantification at screening.
- •16.Patients with serological evidence of hepatitis C virus infection (HCV) should have com
排除标准
- •Subjects who meet any of the following exclusion criteria are not to be enrolled in this study. Additional indication-specific exclusion criteria for 1000 mg BID Dose Escalation Cohort and Phase 2 are provided in Appendix 3.
- •1)History or evidence of clinically significant disorder, condition, or disease that, in the opinion of the investigator or medical monitor would pose a risk to subject safety or interfere with the study evaluations, procedures, or completion.
- •2)Dose Escalation Cohorts: History of = Grade 3 AEs during prior treatment with an immune checkpoint inhibitor, or history of discontinuation of treatment with an immune checkpoint inhibitor due to AEs.
- •3)Dose Escalation 1000 mg BID and Dose Expansion Cohorts: Prior treatment with an immune checkpoint inhibitor (anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies).
- •4)History of autoimmune disease (for example, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis).
- •5)Positive serum pregnancy test (Appendix 5).
- •6)Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry, have no evidence of new or enlarging brain metastases and if taking corticosteroids, are on stable or decreasing doses for at least 7 days from first dose of study drug.
- •7)Uncontrolled intercurrent illness including, but not limited to, active uncontrolled infection, active or chronic bleeding event within 28 days prior to first dose of study drug, or psychiatric illness/social situation that would limit compliance with study requirements as judged by treating physician.
- •8)Myocardial infarction, symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or serious uncontrolled cardiac arrhythmia within the last 6 months of first dose of study drug.
- •9)Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (i.e., larger than what is required for placement of central venous access, percutaneous feeding tube, or biopsy) within 28 days of the first dose of study drug.
- •10)Impairment of GI function or GI disease that may significantly alter the absorption of GS-4224, including any unresolved nausea, vomiting, or diarrhea that is Common Terminology Criteria for Adverse Events (CTCAE) Grade > 1.
- •11)Symptomatic ascites or pleural effusion. A patient who is clinically stable following treatment for these conditions (including thora- or paracentesis) is eligible.
- •12)Minor surgical procedure(s) within 7 days of enrollment, or not yet recovered from prior surgery (placement of central venous access device, fine needle aspiration, or endoscopic biliary stent = 1 day before enrollment is acceptable).
- •13)Prior systemic radiation therapy completed within 4 weeks of the first dose of study drug, prior local radiation therapy completed within 2 weeks of Cycle 1 Day 1 (C1D1), or radiopharmaceuticals (strontium, samarium) within 8 weeks of C1D1.
- •14)Antitumor therapy (chemotherapy, antibody therapy, molecular targeted therapy) within 21 days or 5 half-lives, whichever is longer, of stu
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