A Phase 3 study of pembrolizumab (MK-3475) with or without lenvatinib (E7080/MK-7902) as 1L intervention in a PD-L1 selected population with Recurrent Metastatic Head and Neck Cancer (LEAP-010)
- Conditions
- Recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC)MedDRA version: 21.1Level: PTClassification code 10063569Term: Metastatic squamous cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003717-34-IT
- Lead Sponsor
- MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 500
1.Has histologically confirmed diagnosis of R/M HNSCC that is considered incurable by local therapies. 2. Has a primary tumor location of oropharynx, oral cavity, hypopharynx, or larynx. 3 Is male or female, and at least 18years of age at the time of signing the informed consent. 4. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 30 days after
the last dose of lenvatinib/placebo:Be abstinent from heterosexual intercourse as their preferred and
usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent, or Must agree to use contraception unless confirmed to be azoospermic(vasectomized or secondary to medical cause) as detailed below:Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with aWOCBP who is not currently pregnant. Please note that 30 days after lenvatinib is stopped, if the participant ison pembrolizumab only, no male contraception measures are needed.5.A female participant is eligible to participate if she is not pregnant orbreastfeeding, and
at least one of the following conditions applies:Is not a WOCBP ORIs a WOCBP and using a contraceptive method that is highly effective(with a failure rate of <1% per year), with low user dependency, or be
abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) during theintervention period and for at least 120 days post pembrolizumab or 30
days post lenvatinib/placebo whichever occurs last. The investigatorshould 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 (urineor serum asrequired by local regulations) within 24 hours before thefirst 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, theparticipant must be excluded from participation if the serum pregnancyresult is positive.6.The participant (or legally acceptable representative if applicable)provides written informed consent/assent for the study.7.Has measurable disease per RECIST 1.1 as assessed by BICR.8.Has provided an archival tumor tissue sample or newly obtained coreor incisional biopsy of a tumor lesion not previously irradiated. FFPE
tissue blocks are preferred to slides. Newly obtained biopsies arepreferred to archived tissue.9.Has a PD-L1 positive (CPS =1) tumor as determined by the centrallaboratory.10.Participants with oropharyngeal cancer must have results fromtesting of HPV status defined as p16 IHC testing using CINtec® p16Histology assay and a 70% cutoff point. If HPV status was previouslytested using this method, no additional testing is required.11.Has an ECOG performance score of 0 to 1.12.Has adequately controlled BP with or without antihypertensivemedications, defined as BP =150/90 mm Hg with no change inantihypertensive medications within 1 week prior to randomization.13.Has adequate organ function as defined in the protocol. Specimens
must be collected within 7 days prior to the start of study intervention.
Are the trial subjects under 18? no
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 325
F.1.3 Elderly (>=65 years) yes
F.1.3.1
1.Has any evidence of symptoms or signs of active tumor bleedingwithin 6 months prior to randomization.2Has radiographic evid of major blood vessel invasion/infiltrationor tumor demonstrates >90 degree abutment or encasement of a majorblood vessel.3.Has a history of re-irradiation to any head and neck sites of diseaseincluding thecervical, infraclavicular or supraclavicular lymph nodes forhead and neck cancer.4.Has ulceration and/or fungation of disease onto the skin surface.5 Has a history of anycontraindication or has a sev hypersensitivityto any components of pembrolizumab (=Grade 3) or lenvatinib.6.Has preexisting =Grade 3 gastrointestinal or non-gastrointestinalfistula.7.Has a history of a gastrointestinal condition or procedure that, in theopinion of the investigator, may affect oral study drug absorption.8.Has clinically significant cardiovascular impairment within 12 monthsof the first dose of study drug, such as history of congestive heart failuregreater than NYHA Class II, unstable angina, myocardial infarction orcerebrovascular accident/TIA/stroke, cardiac revascularization, orcardiac arrhythmia associated with hemodynamic instability.9.Has disease that is suitable for local therapy administered withcurative intent.10 Had PD within 6 months of completion of curatively intendedsystemic treatment for locoregionally advanced HNSCC.11.Has had major surgery within 3 weeks prior to first dose of studyinterventions.12.Has difficulty swallowing capsules or ingesting a suspension eitherorally, by a nasogastric (NG) tube or by a gastrostomy tube.13.Has received prior therapy with lenvatinib or pembrolizumab.14.Received last dose of systemic therapy for locoregionally advanceddisease less than 6 months prior to signing consent15.Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PDL2agent or with an agent directed to another stimulatory or coinhibitoryT-cell receptor ( CTLA-4,OX- 40,CD137).16.Has received prior systemic anticancer therapy includinginvestigational agents within 4 weeks prior torandom.17.Hasreceived prior radiotherapy within 2 weeks of start of studyintervion.18 Has received a live vaccine within 30days prior to the first dose ofstudy drug.19.Iscurrently participating in or has participated in a study of aninvestigational agent or has used an investigational device within 4weeks prior to the first dose of study intervention.20.Has urine protein =1 g/24 hours.21.Has prolongation of QTc interval (calculated using Fridericia'sformula) to >480 msec.22.Has a LVEF below the institutional (or local laboratory) normalrange, as determined by MUGA or ECHO.23.Has a diagnosis of immunodeficiency or is receiving chronic systemicsteroid therapy (in dosing exceeding 10 mg daily of prednisoneequivalent) or any other form of immunosuppressive therapy within 7days prior the first dose of study drug.24.Has a known additional malignancy that is progressing or hasrequired active treatment within the past 3 years.25.Has known active CNS metastases and/or carcinomatous meningitis.Participants with previously treated brain metastases may participateprovided they are radiologically stable, (ie, without evidence ofprogression) for at least 4 weeks by repeat imaging (note that therepeat imaging should be performed during study screening), clinicallystable and without requirementof steroid treatment for at least 14 daysprior to first dose of study intervention.26. Has an active autoimmune disease that has required systemictreatment i
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method