Adjuvant Therapy with Pembrolizumab versus Placebo in Resected High-risk Stage II Melanoma

Phase 1

Conditions: High-risk Stage II melanoma
MedDRA version: 21.1Level: LLTClassification code 10053571Term: MelanomaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-000669-35-BE

Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 954

Inclusion Criteria

1. Male/female participants who are =12 years of age on the day of providing documented informed consent/assent [unless local regulations and/or institutional policies do not allow for participants <18 years of age to participate; for those sites, the eligible population is =18 years of age] with surgically resected and histologically/pathologically confirmed new diagnosis of Stage IIB or IIC cutaneous melanoma per AJCC 8th edition guidelines.
2. Participants must not have been previously treated for melanoma beyond complete surgical resection.
3. No more than 12 weeks may elapse between final surgical resection and randomization. Treatment should start only after complete wound healing from the surgery. If there is a delay of 1 to 7 days exceeding 12 weeks due to unforeseen circumstances, the eligibility should be discussed with the Sponsor and the decision documented. A delay of 1 to 7 days for screening imaging requirements will be allowed if sponsor has allowed 1 week extension between surgical resection and randomization.
4. Have no evidence of metastatic disease on imaging as determined by investigator assessment. All suspicious lesions amenable to biopsy should be confirmed negative for malignancy
5. Have a performance status of 0 or 1 on the ECOG Performance Scale at the time of enrollment, LPS score =50 (for participants =16 years old.), or a KPS score =50 (for participants >16 and <18 years old)
6. Participant must have recovered adequately from toxicity and/or complications from surgery prior to starting study treatment
7. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
a.) Is not a woman of childbearing potential (WOCBP)
OR
• Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year) or be abstinent from heterosexual
intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) as described in Appendix 3 during the
intervention period and for at least 120 days after the last dose of study intervention. The investigator should evaluate the
potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
• A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 72 hours before the
first dose of study intervention.
• If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the
participant must be excluded from participation if the serum pregnancy result is positive.
• Abstains from breastfeeding during the study treatment period and for at least 120 days after study treatment.
• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
• Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those
participating in clinical studies.
8. The participant (or legally acceptable representative if applicable) provides documented informed consent/assent for the study and agrees to distant metastasis-free survival (DMFS) and Overall Survival (OS) data collection until these study endpoints are reached
9. The participant provides consent/assent for future biomedical r

Exclusion Criteria

1. Has a known additional malignancy that is progressing or has required active antineoplastic therapy (including hormonal) within the past 5 years
2. 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 drug
3. If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
4. A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
5. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137)
6. Has received prior systemic anticancer therapy for melanoma including investigational agents
7. Has received a live vaccine within 30 days prior to the first dose of study drug. Note: administration of killed vaccines is allowed.
8. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
9. Has severe hypersensitivity (=Grade 3) to any pembrolizumab excipients
10. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
11. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
12. Has an active infection requiring systemic therapy
13. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority
14. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen reactive) or known active Hepatitis C virus (defined as Hepatitis C virus RNA [qualitative] is detected) infection. No testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority
15. Has a history of active tuberculosis (Bacillus tuberculosis)
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
17. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study
18. Has had an allogeneic tissue/solid organ transplant

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare Recurrence-free Survival (RFS) between treatment arms;Secondary Objective: 1) To compare Distant Metastases-free Survival (DMFS) between treatment arms<br>2) To compare Overall Survival (OS) between treatment arms<br>3) To assess the safety and tolerability of pembrolizumab compared to placebo in the proportion of adverse events (AEs);Primary end point(s): Recurrence-free survival (RFS);Timepoint(s) of evaluation of this end point: RFS: time from randomization to (1) any recurrence (local or regional [including invasive ipsilateral tumor and invasive loco regional tumor], or distant) as assessed by the investigator, or (2) death due to any cause (both cancer and non-cancer causes of death)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Distant Metastasis-free Survival (DMFS)<br>2. Overall Survival (OS);Timepoint(s) of evaluation of this end point: • OS: The time from randomization to death due to any cause. <br>• DMFS: The time from randomization to appearance of a distant metastasis as assessed by the investigator. A distant metastasis refers to cancer that has spread from the original (primary) tumor to distant organs or distant lymph nodes

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