Brief Summary:
The primary purpose of this study is to compare pembrolizumab/vibostolimab to pembrolizumab
with respect to recurrence-free survival (RFS). The primary hypothesis is that
pembrolizumab/vibostolimab is superior to pembrolizumab with respect to RFS as assessed by
the investigator in participants with high-risk resected Stage IIB, IIC, III and IV melanoma.
Inclusion Criteria:
- Has surgically resected and histologically or pathologically confirmed diagnosis of
Stage IIB and IIC (pathological or clinical), III, or IV cutaneous melanoma per the
American Joint Committee on Cancer (AJCC) eighth edition guidelines
- Has not received any prior systemic therapy for melanoma beyond surgical resection
- Has had no more than 12 weeks between final surgical resection and randomization
- Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV
on anti-retroviral therapy (ART)
- Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they
have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have
undetectable HBV viral load before randomization
- Participants with history of hepatitis C virus (HCV) infection are eligible if HCV
viral load is undetectable at screening
Exclusion Criteria:
- Has ocular, mucosal, or conjunctival melanoma
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior the first dose of study medication
- Has not adequately recovered from major surgical procedure or has ongoing surgical
complications
- Has received prior radiotherapy within 2 weeks of start of study intervention or has
had a history of radiation pneumonitis
- Received a live or live attenuated vaccine within 30 days before the first dose of
study intervention. Administration of killed vaccines is allowed
- Has received an investigational agent or has used an investigational device within 4
weeks before study intervention administration
- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease
- Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years
- Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis
- Has an active autoimmune disease that has required systemic treatment in past 2 years
- Has an active infection requiring systemic therapy
- Has had an allogenic tissue/solid organ transplant
Primary outcome:
1. Recurrence-Free Survival (RFS) (Time Frame - Up to approximately 52 months):
RFS is defined as the time from randomization to any recurrence (local, locoregional, regional, or distant) as assessed by the investigator, or death due to any cause, whichever occurs first. The RFS as assessed by the investigator will be reported for all randomized participants.
Secondary outcome:
1. Distant Metastasis-Free Survival (DMFS) (Time Frame - Up to approximately 68 months):
DMFS is defined as the time from randomization to the first diagnosis of a distant metastasis, or death due to any cause, whichever occurs first. Distant metastasis refers to cancer that has spread from the original (primary) tumor and beyond local tissues and lymph nodes to distant organs or distant lymph nodes. The DMFS as assessed by the investigator will be reported for all randomized participants.
2. Overall Survival (OS) (Time Frame - Up to approximately 96 months):
OS is defined as the time from randomization to death due to any cause.
3. Number of Participants Who Experienced at Least One Adverse Event (AE) (Time Frame - Up to approximately 15 months):
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
4. Number of Participants Who Discontinued Study Treatment Due to an AE (Time Frame - Up to approximately 12 months):
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
5. Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score (Time Frame - Baseline and up to approximately 72 months):
The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to Items 29 and 30 ("How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1=Very Poor to 7=Excellent). A higher score indicates a better overall outcome. Change from baseline in the score of EORTC QLQ-C30 Items 29 and 30 will be presented.
6. Change from Baseline in the EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score (Time Frame - Baseline and up to approximately 72 months):
The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a worse level of function. Change from baseline in the score of EORTC QLQ-C30 Items 1-5 will be presented.
7. Change from Baseline in the EORTC QLQ-C30 Role Functioning (Items 6 and 7) Combined Score (Time Frame - Baseline and up to approximately 72 months):
The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 2 questions about their role functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a worse level of function. Change from baseline in the score of EORTC QLQ-C30 Items 6-7 will be presented.
- Experimental: Pembrolizumab/Vibostolimab
Participants receive pembrolizumab/vibostolimab (coformulation of 200 mg pembrolizumab and 200 mg vibostolimab) via intravenous (IV) infusion on Day 1 of each cycle (cycle length = 3 weeks) for up to 17 cycles (up to ~1 year). - Active Comparator: Pembrolizumab
Adult participants receive 200 mg and adolescent participants ≥40 kg receive 2 mg/kg (up to a max of 200 mg) pembrolizumab via IV infusion on Day 1 of each cycle (cycle length = 3 weeks) for up to 17 cycles (up to ~1 year).
- Pembrolizumab/Vibostolimab (MK-7684A):
Co-formulation of pembrolizumab 200 mg/20 mL vial and vibostolimab 200 mg administered as IV infusion for up to 17 administrations - Pembrolizumab (MK-3475 / KEYTRUDA® / ):
Pembrolizumab 25 mg/mL administered as IV infusion for up to 17 administrations
Quelle: ClinicalTrials.gov
