Adjuvant Therapy with Pembrolizumab versus Placebo in Resected Highrisk 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-IT
• Lead Sponsor: MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-20
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 954

Inclusion Criteria

1. Male/female participants who are =12 years of age on the day of signing 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 male participant must agree to use contraception as detailed in Appendix 3 of the protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period
8. A female participant is eligible to participate if she is not pregnant (see Appendix 3 of the protocol), not breastfeeding, and at least one of the following conditions applies:
a.) Not a woman of childbearing potential (WOCBP) as defined in Appendix 3
OR
b.) A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days after the last dose of study treatment
9. The participant (or legally acceptable representative if applicable) provides written 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
10. The participant provides consent/assent for future biomedical research. However, the participant may take part in the main study without participating in future biomedical research
11. Have adequate organ function as defined in the protocol. Specimens must be collected within 10 days prior to the start of study treatment.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 810
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 142

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 or treatment allocation (see Appendix 5 of the protocol). 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-PDL2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137)
6. Has received prior systemic anti-cancer therapy for melanoma including investigational agents
7. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not 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. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with t

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: <br>To compare Recurrence-free Survival (RFS) between treatment arms.;Secondary Objective: <br>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<br>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: • 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.<br><br>• OS: The time from randomization to death due to any cause.