EUCTR2014-003277-42-PT进行中（未招募）1 期
A Phase I/II Study of MCLA-128, a full length IgG1 Bispecific Antibody Targeting HER2 and HER3, in Patients with Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Merus N.V.
- 入组人数
- 228
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
- •General Inclusion Criteria Part 1+2
- •1. Age =18 yrs
- •2. =1 measurable lesion, RECIST v1.1
- •3. ECOG 0-1
- •4. life expectancy =12 wks
- •5. Toxicities of previous anti-cancer therapy resolved to =Gr 1, except for alopecia, lymphopenia assessed as non-clinically significant, Gr 2 sensory neurotoxicity
- •6. =4-wks between last radiotherapy and D1 (except =1X8 Gy for pain palliation)
- •7. Complete recovery from major surgery
- •8. Screening Labvalues
- •a. neutrophil count =1.5 x 10^9/L without colony stimulating factor support
- •b. Platelets =100 x 10^9/L
- •c. Hemoglobin =9 g/dL or =2.2 mmol/L (not transfusion dependent)
- •d. Total bilirubin <1.5 ULN (unless Gilbert’s syndrome)
- •e. AST(SGOT) =2.5 x ULN; ALT(SGPT) =2.5 x ULN; =5 x ULN for patients with advanced solid tumors with liver metastases; patients with confirmed bony metastases are permitted with isolated elevations in ALP >5 x ULN
- •f. Serum creatinine = 1.5 x ULN or estimated GFR of >50 mL/min Cockroft-Gault
- •g. Coagulation function (INR and aPTT =1.5 ULN, unless on therapeutic anticoagulants)
- •h. Urine protein dipstick = 2+ ; or =100 mg/24 hrs urine
- •9. Able to provide at baseline a mandatory archival tumor sample from fresh (preferred) or archival tissue
- •10. Negative pregnancy test at Screening and =7 days of D1
- •11. Sexually active male and female patients of childbearing potential must agree to use an effective method of birth control during entire study and 6 months after final administration of MCLA-128
- •12. give written informed consent
- •13. Capable of understanding protocol requirements, is willing and able to comply with study procedures and has signed the main informed consent document. For any optional biopsy sampling (tissue and/or blood) and long-term sample storage, additional consent is required
- •14. Patient with metastatic cancer who has disease progression after having received treatment with all available therapies known to convey clinical benefit
- •Specific Inclusion Criterion Part 1
- •15. Histologically-confirmed and documented advanced/metastatic epithelial tumors, relapsed/refractory to =2 prior regimens of standard treatment(s), or for which no curative therapy is available and MCLA-128 is a reasonable treatment option
- •Specific Inclusion Criterion Part 2:
- •Group A (BC)
- •16. Histologically-confirmed and documented advanced/metastatic breast cancer (BC), relapsed/refractory to =2 prior HER2 directed regimen for breast cancer
- •17. Confirmed HER2 amplification (HER2 2+ by IHC confirmed by FISH, or HER2 3+ by IHC) based on historical pathology report or analysis of baseline fresh/archival tumor sample
- •Group B (CRC)
- •18. Histologically-confirmed and documented advanced/metastatic colorectal cancer (CRC), relapsed/refractory to at least 2 prior regimens of standard treatments for metastatic CRC, including 1anti-EGFR treatment (if RASWT)
- •19. Confirmed HER2 amplification based on historical pathology report prior to commencing screening assessments
- •Group C (OC)
- •20. Histologically-confirmed and documented advanced/metastatic epithelial ovarian cancer (OC) for which no curative therapy is available
- •21. Prior therapy including all available standard therapies and =1 platinium based chemotherapy
- •Group D (GC or GEC)
- •22. Histologically-confirmed and documented advanced/metastatic gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEC)
- •23. Prior chemotherapy including platinium and fluoropyrimidine based treatment and trastuzumab
- •24. Confirme
排除标准
- •General Exclusion Criteria for Part 1 and Part 2
- •1. Pregnant or lactating;
- •2. Presence of an active infection or an unexplained fever greater than 38.5°C during Screening up to the first scheduled day of dosing. At the discretion of the Investigator, patients with tumor fever may be enrolled;
- •3. Known hypersensitivity to any of the components of MCLA-128 or history of severe hypersensitivity reactions to human or humanized monoclonal antibodies, including therapeutic antibodies;
- •4. Known HIV, Hepatitis B or Hepatitis C; patients who have previously been treated for Hepatitis C and have undetectable viral loads are eligible;
- •5. Any untreated central nervous system (CNS) lesion. However, patients are eligible if: a) all known CNS lesions have been treated with radiotherapy and/or surgery and b) patient remained without evidence of CNS disease progression = 4 weeks after treatment and c) patients must be off corticosteroid therapy for = 3 weeks;
- •6. Patients with leptomeningeal metastases
- •7. Previous or concurrent malignancy (excluding non-basal cell carcinoma of skin or carcinoma in situ of the uterine cervix) unless the tumor was treated with curative intent more than 2 years prior to study entry;
- •8. Prior anti-tumor therapy including:
- •a. Approved anti-HER2 therapies and/or anti-EGFR approved therapies within 28 days prior to the first scheduled day of dosing with MCLA-128;
- •b. Investigational therapy administered within 28 days prior to the first scheduled day of dosing with MCLA-128. Dosing with MCLA-128 within 28 days of receiving investigational therapy is acceptable once a time interval equal to at least five half-lives of the investigational agent has passed or in case of prior checkpoint inhibitory treatment;
- •c. Treatment with chemotherapy agents within 28 days prior to the first scheduled day of dosing with MCLA-128;
- •9. Presence of NYHA Class III or IV congestive heart failure or LVEF <50% or history of significant cardiac disease, unstable angina, congestive heart failure, myocardial infarction, or ventricular arrhythmia requiring medication;
- •10. Presence of any other medical or psychological condition deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate or participate in the study, or interfere with the interpretation of the results.
研究者
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