A Multicenter, Randomized, Controlled, Three-Arm, Phase III Study to Evaluate the Safety and Efficacy of Two Dosing Schedules of Pembrolizumab (MK-3475) Compared to Ipilimumab in Patients with Advanced Melanoma

Phase 3

Completed

• Conditions: Cancer; Melanoma; 10040900

• Registration Number: NL-OMON44956
• Lead Sponsor: Merck Sharp & Dohme (MSD)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 18

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 as indicated by the protocol.;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
device, diaphragm with spermicide, cervi

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.;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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The following evaluations will be performed throughout the course of the study<br /><br>(see flowchart, 1.7 of protocol for more details):<br /><br>- Tumor resonse assessments by physical examination, and tumor imaging by CT or<br /><br>MRI<br /><br>- Anti-MK3475 antibodies (MK3475 patients only)<br /><br>- PK measurements (PK peak/trough)<br /><br>- ECOG performance status<br /><br>- Tumor biopsies<br /><br>- EORTC QLQ-C30 / EuroQol EQ-5D<br /><br>- Health Economic Assessment</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>N/A</p><br>