MK-3475 Compared to Ipilimumab in Patients with Advanced Melanoma
- Conditions
- Patients with advanced MelanomaTherapeutic area: Diseases [C] - Cancer [C04]MedDRA version: 19.0Level: LLTClassification code 10053571Term: MelanomaSystem Organ Class: 100000004864
- Registration Number
- EUCTR2012-004907-10-GB
- Lead Sponsor
- Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. (hereafter referred to as the SPONSOR or Merck)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 834
1) Patient must have a histologically confirmed diagnosis of unresectable stage III or metastatic MEL not amenable to local therapy.
Patient may not have a diagnosis of uveal or ocular melanoma.
Patients who have not received prior systemic treatment (excluding adjuvant or neoadjuvant therapy) for MEL (first line) or who have received prior systemic treatment (excluding adjuvant or neoadjuvant therapy) for MEL (second line) are both eligible. However, the enrollment of either first line or second line patients will be limited to approximately 387 patients. After this limit is reached for either of the group, only patients from the other group will be enrolled.
Patients must have testing for BRAF mutation prior to study entry. Patients with BRAF V600E mutant melanoma may have received prior BRAF inhibitor therapy as first-line systemic therapy and be eligible for this study as second line treatment. At the discretion of the investigator, patients with BRAF V600E mutant melanoma who have NOT received a BRAF inhibitor are also eligible for this study as first line treatment if they meet the following additional criteria:
-LDH-No clinically significant tumour related symptoms in the judgement of the investigator
-Absence of rapidly progressing metastatic melanoma in the judgement of the investigator
2) Patient is male or female and =18 years of age on day of signing informed consent.
3) Patient must have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale (Appendix 6.4).
4) Patient must have adequate organ function as indicated by the following laboratory values.
SystemLaboratory Value
Hematological:
Absolute neutrophil count (ANC)=1,500 /mcL
Platelets=100,000 / mcL
Hemoglobin=9 g/dL or =5.6 mmol/L–
Renal
Serum creatinine=1.5 X upper limit of normal (ULN)
Hepatic
Serum total bilirubin= 1.5 X ULN OR
Direct bilirubin = ULN for patients with total bilirubin levels > 1.5 ULN
AST (SGOT) and ALT (SGPT)= 2.5 X ULN OR
= 5 X ULN for patients with liver metastases
Coagulation
International Normalized Ratio (INR) or Prothrombin Time (PT)
Activated Partial Thromboplastin Time (aPTT)=1.5 X ULN unless patient is receiving anticoagulant therapy
as long as PT or PTT is within therapeutic range of intended use of anticoagulants
=1.5 X ULN unless patient is receiving anticoagulant therapy
as long as PT or PTT is within therapeutic range of intended use of anticoagulants
5) Patient has a tumour sample (archival or newly obtained biopsy) that is adequate for PD-L1 assessment prior to randomisation. Patients must submit the tumour sample during screening for PD-L1 expression testing at a central pathology laboratory. Patients will be eligible to participate regardless of the level of PD-L1 expression, but will be stratified by PD-L1 expression level (high or low PD-L1 expression level) at the time of randomisation. Patient who do not submit a sample adequate for PD-L1 determination will not be randomised. Patients with an inadequate archival sample may obtain a new biopsy and patients with an inadequate newly obtained biopsy may undergo re biopsy at the discretion of the investigator.
6) Female patient of childbearing potential has a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the patien
1) Patient had prior treatment with IPI or other anti-CTLA-4 agent, any anti-PD-1, anti-PD-L1, or anti- PD-L2 agent.
2) Patient who has had chemotherapy, radioactive, or biological cancer therapy within four weeks prior to the first dose of study drug, or who has not recovered to CTCAE Grade 1 or better from the AEs due to cancer therapeutics administered more than four weeks earlier.
3) Patient is currently participating or has participated in a study of an investigational agent or using an investigational device within 30 days of the first dose of study drug.
4) Patient is expected to require any other form of systemic or localized antineoplastic therapy while on study.
5) Patient is on any systemic steroid therapy within one week before the planned date for first dose of randomized treatment or on any other form of immunosuppressive medication.
6) Patient has a history of a malignancy (other than the disease under treatment in the study) within 5 years prior to first study drug administration. This should exclude adequately treated Stage 1 or Stage 2 basal/squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or other in situ cancers. Shorter intervals can be considered after discussion with Sponsor.
7) Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by MRI for at least four weeks prior to the first dose of study drug), have no evidence of new or enlarging brain metastases and are off systemic steroids for at least two weeks.
8) Patient previously had a severe hypersensitivity reaction to treatment with another mAb.
9) Patient has an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents. Patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Patients with hypothyroidism stable on hormone replacement will not be excluded from the study.
10) Patient has an active infection requiring systemic therapy.
11) Patient has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
12) Patient has a known history of or is positive for Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA [qualitative] is detected).
13) Patient has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient’s participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator.
14) Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
15) Patient is, at the time of signing informed consent, a regular user (including recreational use”) of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).
16) Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
17)Patient has received a live vaccine within 30 days prior to first dose.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method