A Multicenter, Randomized Phase III study of MK-3475 Compared to Ipilimumab in Patients with Advanced Melanoma

Phase 1

• Conditions: Patients with advanced Melanoma; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-004907-10-NL
• 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

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-08-13
• Study Completion: 2019-06-03
• Last Update Posted: 3 November 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 834

Inclusion Criteria

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 one 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 (60% of the total patients). After this limit is reached for either of the groups, only patients from the other group will be enrolled.
• Patients must have testing for a 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 < local ULN
• No clinically significant tumor related symptoms in the judgment of the investigator
• Absence of rapidly progressing metastatic melanoma in the judgment of the investigator
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 tumor sample (archival or newly obtained biopsy) that is adequate for PD-L1 assessment prior to randomization. Patients must submit the tumor 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 randomization. Patients who do not submit a sample adequate for PD-L1 determination will not be randomized. 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.

Patient has at least one measurable lesion per RECIST criteria on imaging studies (CT or MRI). Cutaneous lesions and other superficial lesions that are detectable only by physical examination are not considered measurable lesions for the purposes of this protocol, but may be considered as non-target lesions.

Are

Exclusion Criteria

1Patient had prior treatment with IPI or other anti-CTLA-4 agent, any anti-PD-1, anti-PD-L1, or anti- PD-L2 agent.
2Patient 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.
3Patient 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.
4Patient is expected to require any other form of systemic or localized antineoplastic therapy while on study.
5Patient is on any systemic corticosteroid therapy within one week before the planned date for first dose of randomized treatment or on any other form of immunosuppressive medication.
6Patient 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.
7Patient 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.
8Patient previously had a severe hypersensitivity reaction to treatment with another mAb.
9Patient 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.
10Patient has an active infection requiring systemic therapy.
11Patient has known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
12Patient has a known history of or is positive for Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA [qualitative] is detected).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified