A Phase III Study to Evaluate the Safety and Efficacy of MK-3475 Compared to Ipilimumab in Patients with Advanced Melanoma.

Phase 1

• Conditions: Patients with advanced Melanoma; MedDRA version: 20.0 Level: LLT Classification code 10053571 Term: Melanoma System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-004907-10-DE
• 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: 2013-07-31
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 645

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
2) Patient is male or female and =18 years of age on day of signing informed consent, either by the patient or a parent or legal guardian.
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.
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.
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 patient to be eligible.
7) Female patients enrolled in the study, who are not free from menses for >18 months, post hysterectomy/oophorectomy, or surgically sterilized, must be willing to use either 2 adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy or to abstain from heterosexual activity throughout the study, starting with Visit 1 through 120 days after the last dose of study therapy. Approved contraceptive methods include 2 of the following barrier methods or one barrier method combined with a hormonal contraceptive: intra uterine de

Exclusion Criteria

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. (A patient in the Survival Follow up phase of an investigational agent where no further treatment is expected is eligible).
4 Patient is expected to require any other form of systemic or localized antineoplastic therapy while on study.
5 Patient 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.
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 ½ 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 (wit

Study & Design

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