A Phase 3 study of Pembrolizumab or placebo as adjuvant therapy after surgical removal of a high-risk melanoma at stage II.
Zusammenfassung der Studie
The immune system plays an important role in tumor control. Pembrolizumab is an antibody that interrupts or ends the deception of the immune system by the tumor, thereby enhancing its own fighting ability, particularly when the tumor has a feature (the so-called PD-L1). The study investigates the adjuvant (supportive) effect of Pembrolizumab compared to a placebo (dummy medication, containing no active substance) after surgical removal of a stage II melanoma and aims to find out whether Pembrolizumab can delay the recurrence of the disease. The total duration of the study is approximately 15 years (1 year of treatment with the study medication; followed by monitoring with the possibility of re-treatment if the disease recurs).
(BASEC)
Untersuchte Intervention
This study is expected to involve nearly 1000 patients.
After a thorough eligibility assessment, collection of medical history, and detailed information, the participant is included in the study and randomly assigned to one of the two treatment arms (treatment with Pembrolizumab or treatment with placebo). The probability of being assigned to the Pembrolizumab treatment group is 50%. Neither the study doctor nor the participant knows about the assignment and the therapy applied (the study is so-called "double-blind").
In the first part of the study, participants receive Pembrolizumab or placebo intravenously every three weeks (depending on the assigned group) for 17 cycles. During this period, their health status will be regularly monitored for any recurrence of the disease using imaging studies.
If the disease recurs, the study participant will be unblinded (i.e., both the doctor and the participant will now know which treatment group they were assigned to).
Under certain circumstances, a study participant may also participate in the second part of the study in case of disease recurrence. Here, they receive Pembrolizumab every three weeks (up to 17 or 35 cycles, depending on diagnosis).
During study visits, various measures and examinations may take place:
Discussion of well-being and current medication, intravenous therapy, imaging procedures (CT and/or MRI scans), electrocardiogram (ECG), samples of blood, urine, or tissue, questionnaires, and examination of vital signs (pulse, blood pressure, etc.).
Follow-Up Phase:
Participants from the first and second parts of the study enter the follow-up phase after complete treatment or after study discontinuation for reasons other than disease progression, where they will be monitored in the first year every 12 weeks, in years 2-5 every 6 months, and then annually.
Participants who cannot or do not wish to participate in the second part of the study but begin a new cancer treatment due to local recurrence or distant metastases will be contacted by the study team approximately every 12 weeks or more frequently to inquire about their health status.
(BASEC)
Untersuchte Krankheit(en)
Study participants are being investigated who have had a cutaneous melanoma (black skin cancer) at stage IIB or IIC surgically removed before the start of the study. The study must begin within 12 weeks after complete tumor removal. Clinical research data indicate that this population has a medical need for adjuvant therapy after surgical removal of the tumor. The aim of this so-called adjuvant therapy is to prevent a recurrence of the disease and to increase the survival rate, with the therapeutic benefit of Pembrolizumab already demonstrated in patients with more advanced melanomas.
(BASEC)
• Male or female study participants with surgically removed and histologically/pathologically confirmed new diagnosis of cutaneous melanoma at stage IIB or IIC. • Study participants have not been treated for this cancer (e.g., radiation) other than complete surgical removal of the current primary melanoma. • No more than 12 weeks may elapse between the complete surgical removal of the melanoma and the first study treatment. (BASEC)
Ausschlusskriterien
• Known additional malignant cancer that is progressing or required active antineoplastic (growth-inhibiting, e.g., hormonal) therapy or surgical intervention within the last 5 years. • Diagnosed immunodeficiency, long-term systemic steroid treatment (> 10 mg daily prednisone or equivalent) or any other form of immunosuppressants within 7 days prior to the first administration of the study medication. • Insufficient wound healing and recovery from the effects of surgery at the start of the study treatment. (BASEC)
Studienstandort
Basel, Bellinzona, Bern, Chur, Genf, Lausanne, Sion, St Gallen, Zürich
(BASEC)
Sponsor
MSD Merck Sharp & Dohme AG Luzern
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Klaudia Georgi
+41 79 512 34 39
klaudia.georgi@cluttermsd.comMerck Sharp & Dohme LLC 126 East Lincoln Ave. P.O. Box 2000 07065 Rahway, New Jersey USA
(BASEC)
Allgemeine Auskünfte
Merck Sharp & Dohme LLC
(ICTRP)
Wissenschaftliche Auskünfte
Merck Sharp & Dohme LLC
(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Zürich
(BASEC)
Datum der Bewilligung durch die Ethikkommission
06.09.2018
(BASEC)
ICTRP Studien-ID
NCT03553836 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
Adjuvant Therapy with Pembrolizumab versus Placebo in Resected Highrisk Stage II Melanoma: A Randomized, Double-blind Phase 3 Study (KEYNOTE 716) (BASEC)
Wissenschaftlicher Titel
Adjuvant Therapy With Pembrolizumab Versus Placebo in Resected High-risk Stage II Melanoma: A Randomized, Double-blind Phase 3 Study (KEYNOTE-716) (ICTRP)
Öffentlicher Titel
Safety and Efficacy of Pembrolizumab Compared to Placebo in Resected High-risk Stage II Melanoma (MK-3475-716/KEYNOTE-716) (ICTRP)
Untersuchte Krankheit(en)
Melanoma (ICTRP)
Untersuchte Intervention
Biological: Pembrolizumab;Other: Placebo (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator). (ICTRP)
Ein-/Ausschlusskriterien
Gender: All
Maximum age: N/A
Minimum age: 12 Years
Inclusion:
- 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
- Has not been previously treated for melanoma beyond complete surgical resection
- Has =12 weeks between final surgical resection and randomization
- Has no evidence of metastatic disease on imaging as determined by investigator
- 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
- Has recovered adequately from toxicity and/or complications from surgery prior to
study start
- 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:
- Has a known additional malignancy that is progressing or has required active
antineoplastic therapy (including hormonal) within the past 5 years with the
exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin,
or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have
undergone potentially curative therapy
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
or any other form of immunosuppressive therapy within 7 days prior to the first dose
of study treatment
- 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
- 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)
- Has received prior systemic anti-cancer therapy for melanoma including
investigational agents
- Has received a live vaccine within 30 days prior to the first dose of study
treatment
- 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
- Has severe hypersensitivity (=Grade 3) to any excipients of pembrolizumab
- Has an active autoimmune disease that has required systemic treatment in the past 2
years
- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis
- Has an active infection requiring systemic therapy
- Has a known history of human immunodeficiency virus (HIV) infection
- 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
- Has a history of active tuberculosis (Bacillus tuberculosis)
- 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
- Has a known psychiatric or substance abuse disorder that would interfere with the
participant's ability to cooperate with the requirements of the study
- Has had an allogeneic tissue/solid organ transplant (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Recurrence-free Survival (RFS) (ICTRP)
Distant Metastasis-free Survival (DMFS);Overall Survival (OS);Number of Participants Who Experienced at Least One Adverse Event (AE);Number of Participants Who Discontinued Study Treatment Due to an AE (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Medical Director, Merck Sharp & Dohme LLC (ICTRP)
Sekundäre IDs
MK-3475-716, KEYNOTE-716, 205203, 2022-501966-23, U1111-1282-6109, 2018-000669-35, 3475-716 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT03553836 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar