A Phase 3 study to assess the safety and efficacy of Pembrolizumab and Lenvatinib versus Pembrolizumab alone as first-line therapy in participants with advanced melanoma
Zusammenfassung der Studie
The immune system plays an important role in tumor control. Pembrolizumab (MK3475) is an antibody that blocks or terminates the inhibition of the immune system by the tumor, thereby enhancing the body's ability to fight the tumor. Lenvatinib is an inhibitor of a molecule that promotes cell growth and the formation of new blood vessels in tumor cells. By inhibiting blood vessel formation, the nutrient supply to the tumor is reduced, thereby slowing tumor growth. This study investigates the efficacy and safety of the combination of Pembrolizumab with Lenvatinib compared to the effect and safety of Pembrolizumab alone in patients with previously untreated advanced melanoma. Study participants will receive the study medication for approximately 2 years. After stopping the study medication, a follow-up phase will follow.
(BASEC)
Untersuchte Intervention
Approximately 660 patients will participate in the study worldwide.
After a thorough eligibility assessment and entry examination, participants will be randomly assigned to one of two treatment groups (Pembrolizumab + Lenvatinib or Pembrolizumab + placebo). The probability of being assigned to the Lenvatinib treatment group is 50%. Until the end of the study, neither the study participant nor the medical staff will know which group the participant is in and therefore whether Lenvatinib or placebo is being administered (the study is said to be "double-blind" regarding Lenvatinib). In case of a medical emergency, the study physician can find out which treatment group the study participant is in.
Treatment phase:
All study participants will receive Pembrolizumab as an infusion every 3 weeks. Additionally, study participants will take either Lenvatinib (20 mg) or placebo orally (tablets) daily. The study treatment lasts about 2 years; thereafter, treatment with Lenvatinib / placebo may continue if the patient has no tumor progression or undesirable side effects. Treatment with Pembrolizumab will be stopped after about 2 years in both treatment arms.
During the study visits, various measures and examinations may be performed: discussions with medical staff, blood draws, blood pressure measurements, electrocardiograms (ECG), weight measurements, urine samples, scans with computed tomography (CT) or magnetic resonance imaging (MRI) with or without intravenous contrast agent.
After treatment completion or study termination, follow-up will occur at 30 and 90 days before the study participant enters the follow-up phase.
Follow-up phase:
If the medication was stopped because the treatment duration of 2 years was reached or for reasons other than disease progression, the participant will continue to be physically examined every 12 weeks during the follow-up.
If the study medication was stopped due to disease progression or the need for a new therapy, the study participant will be contacted every 12 weeks during the follow-up and questioned about their health status.
(BASEC)
Untersuchte Krankheit(en)
Study participants are being sought who have advanced stage melanoma (black skin cancer) and have not yet received any treatment. Melanoma is the most serious form of skin cancer and affects adults of all ages. In Switzerland, melanoma is the fifth most common type of cancer.
(BASEC)
- Histologically or cytologically confirmed melanoma (black skin cancer) - Unresectable melanoma at stage III or IV - The patient has not been treated (with few exceptions) for advanced or metastatic disease so far (BASEC)
Ausschlusskriterien
- Diagnosis of immunodeficiency, chronic systemic treatment with steroids or any other form of immunosuppressive therapy in the past 7 days prior to the start of the study medication - Known other malignant diseases that are progressive and require active treatment - Patients with significant cardiovascular impairment within the last 12 months prior to administration of the first dose of the study medication (BASEC)
Studienstandort
Basel, Chur, Zürich
(BASEC)
Sponsor
Merck Sharp & Dohme AG
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Klaudia Georgi
+41 58 618 33 88
klaudia.georgi@cluttermsd.comMerck Sharp & Dohme AG
(BASEC)
Allgemeine Auskünfte
Merck Sharp & Dohme Corp.
(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Zürich
(BASEC)
Datum der Bewilligung durch die Ethikkommission
30.01.2019
(BASEC)
ICTRP Studien-ID
NCT03776136 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
A Phase 3 Randomized, Placebo-controlled Trial to Evaluate the Safety and Efficacy of Pembrolizumab (MK-3475) and Lenvatinib (E7080/MK-7902) Versus Pembrolizumab Alone as First-line Intervention in Participants with Advanced Melanoma (LEAP-003) (BASEC)
Wissenschaftlicher Titel
A Multicenter, Open-label, Phase 2 Trial to Assess the Efficacy and Safety of Lenvatinib (E7080/MK-7902) in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Melanoma Previously Exposed to an Anti-PD-1/L1 Agent (LEAP-004) (ICTRP)
Öffentlicher Titel
Efficacy and Safety of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) for Advanced Melanoma in Anti-Programmed Death-1/Programmed Death-Ligand 1 (PD-1/L1)-Exposed Participants (MK-7902-004/E7080-G000-225/LEAP-004) (ICTRP)
Untersuchte Krankheit(en)
Advanced Melanoma
(ICTRP)
Untersuchte Intervention
Biological: pembrolizumab
Drug: lenvatinib
(ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Ein-/Ausschlusskriterien
Inclusion Criteria: - Has histologically or cytologically confirmed melanoma - Has unresectable Stage III or Stage IV melanoma per American Joint Committee on Cancer (AJCC) staging system version 8 that is not amenable to local therapy - Has the presence of =1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 as confirmed by BICR. - Has progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies - Has submitted initial imaging - Has an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 - Has provided a baseline tumor biopsy - Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia). If participant received major surgery or radiation therapy of >30 Gray (Gy), they must have recovered from the toxicity and/or complications from the Intervention - Male participants must agree to use approved contraception during the treatment period and for at least 95 days after the last dose of study intervention and refrain from donating sperm during this period - Female participants are not pregnant and not breastfeeding, and are not a woman of childbearing potential (WOCBP) or are a WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 95 days after the last dose of study intervention - Has adequate organ function Exclusion Criteria: - 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 before the first dose of study treatment - Has a known additional malignancy that is progressing or requires active treatment - Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis - Has ocular melanoma - Has known hypersensitivity to active substances or any of their excipients including previous clinically significant hypersensitivity reaction to treatment with another monoclonal antibody - 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) - Has an active infection requiring systemic therapy - Has known history of Human Immunodeficiency Virus (HIV) or HIV 1/2 antibodies - Has known history of or is positive for hepatitis B (hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (HCV RNA qualitative] is detected) - Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis - Has a history of active tuberculosis (Bacillus tuberculosis) - Has presence of a gastrointestinal condition including malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib - Has had major surgery within 3 weeks prior to first dose of study interventions (adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility) - Has a pre-existing Grade =3 gastrointestinal or non-gastrointestinal fistula - Has radiographic evidence of major blood vessel invasion/infiltration - Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug - Has clinically significant cardiovascular disease within 12 months from first dose of study drug, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability - Has received prior radiotherapy within 2 weeks of Cycle 1 Day 1 - Has received a live vaccine within 30 days before 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 a history or has current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the 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 had an allogeneic tissue/solid organ transplant - Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study
Minimum age: 18 Years
Maximum age: N/A
Sex: All (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1)
(ICTRP)
Area Under the Concentration Time Curve of Lenvatinib From Time 0 to Infinity (AUC 0-inf)
Duration of Response (DOR) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1)
Overall Survival (OS)
Percentage of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
Percentage of Participants Who Experience At Least One Adverse Event (AE)
Progression-free Survival (PFS) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1)
(ICTRP)
Registrierungsdatum
13.12.2018 (ICTRP)
Einschluss des ersten Teilnehmers
30.01.2019 (ICTRP)
Sekundäre Sponsoren
Eisai Inc.
(ICTRP)
Weitere Kontakte
Medical Director, Merck Sharp & Dohme Corp. (ICTRP)
Sekundäre IDs
2018-002518-10, 7902-004, E7080-G000-225, LEAP-004, MK-7902-004 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
http://www.who.int/trialsearch/Trial2.aspx?TrialID=NCT03776136 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar