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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Sep 2018 → ongoing

Decision date (initial)

2023-09-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-501966-23-00

EudraCT number

2018-000669-35

WHO UTN

U1111-1282-6109

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacogenomic, Therapy, Others, Pharmacogenetic, Efficacy, Safety, Pharmacodynamic, Pharmacokinetic

To compare Recurrence-free Survival (RFS) between treatment arms.

Secondary objectives 3

1. To compare DMFS between treatment arms.
2. To compare OS between treatment arms.
3. To assess the safety and tolerability of pembrolizumab compared to placebo in the proportion of AEs.

Conditions and MedDRA coding

Resected High-Risk Stage II Melanoma

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Is 12 years or older
2. Has surgically resected and histologically/pathologically confirmed new diagnosis of Stage IIB or IIC cutaneous melanoma per American Joint Committee on Cancer (AJCC) 8th edition guidelines
3. Has not been previously treated for melanoma beyond complete surgical resection
4. Has ≤12 weeks between final surgical resection and randomization
5. Has no evidence of metastatic disease on imaging as determined by investigator
6. Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale or Lansky Play-Performance Scale (LPS) score ≥50 for participants ≤16 years old, or a Karnofsky Performance Scale (KPS) score ≥50 for participants >16 and <18 years old
7. Has recovered adequately from toxicity and/or complications from surgery prior to study start
8. Female participants must not be pregnant or breastfeeding, and must agree to use contraception during the treatment period and for at least 120 days after the last dose of study treatment if they are women of childbearing potential (WOCBP)

Exclusion criteria 15

1. 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
2. Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1), anti-Programmed Cell Death Receptor Ligand 1 (PD-L1) or anti-Programmed Cell Death Receptor Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
3. Has received prior systemic anti-cancer therapy for melanoma including investigational agents
4. Has received a live vaccine within 30 days prior to the first dose of study treatment
5. 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
6. Has severe hypersensitivity (≥Grade 3) to any excipients of pembrolizumab
7. Has an active autoimmune disease that has required systemic treatment in the past 2 years
8. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
9. Has an active infection requiring systemic therapy
10. Has a known history of human immunodeficiency virus (HIV) infection
11. 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 ribonucleic acid [RNA] [qualitative] is detected) infection
12. Has a history of active tuberculosis (Bacillus tuberculosis)
13. 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
14. Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
15. Has had an allogeneic tissue/solid organ transplant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Recurrence-free Survival (RFS)

Secondary endpoints 4

1. Distant Metastasis-free Survival (DMFS)
2. Overall Survival (OS)
3. Number of Participants Who Experienced at Least One Adverse Event (AE)
4. Number of Participants Who Discontinued Study Treatment Due to an AE

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Toshifumi Hoki

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Toshifumi Hoki

Third parties 6

Locations

6 EU/EEA countries · 49 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 87 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

18 submissions — initial application plus substantial / non-substantial modifications