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: 22.0Level: LLTClassification code 10082179Term: Squamous cell carcinoma of head and neck metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003717-34-DE
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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 18 years of age at the time of
documented informed consent.
Male Participants
Contraceptive use by men should be consistent with local regulations
regarding the methods of contraception for those participating in clinical
studies. If the contraception requirements in the local label for any of
the study interventions is more stringent than the requirements above,
the local label requirements are to be followed.
4. Male participants are eligible to participate if they agree to the
following during the intervention period and for at least 7 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 a
WOCBP who is not currently pregnant.
- Please note that 7 days after lenvatinib is stopped, if the participant is
on pembrolizumab only, no male contraception measures are needed.
Female Participants
Contraceptive use by women should be consistent with local regulations
regarding the methods of contraception for those participating in clinical
studies. If the contraception requirements in the local label for any of
the study interventions is more stringent than the requirements above,
the local label requirements are to be followed.
5. A female participant is eligible to participate if she is not pregnant or
breastfeeding, and
at least one of the following conditions applies:
- Is not a WOCBP
OR
- Is 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 the
intervention period and for at least 120 days post pembrolizumab or 30
days post lenvatinib/placebo whichever occurs last. The investigator
should 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 (urine
or serum asrequired by local regulations) within 24 hours before the
first 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, the
participant must be excluded from participation if the serum pregnancy
result is positive.
6. The participant (or legally acceptable representative) has provided
documented informed consent 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 core,
excisional or incisional biopsy of a tumor lesion not previously irradiated.
FFPE tissue blocks are preferred to slides. Newly obtained biopsies are
preferred to archived tissue.
9. Has a PD-L1 positive (CPS =1) tumor as determined by the central
laboratory.
10. Participants with oropharyngeal cancer must have results from
1. Has any evidence of symptoms or signs of active tumor bleeding within 6 months before randomization.
2. Has radiographic evidence of major blood vessel invasion/infiltration
or tumor demonstrates >90 degree abutment or encasement of a major
blood vessel.
3. Has a history of re-irradiation to any head and neck sites of disease
including the cervical, infraclavicular or supraclavicular lymph nodes for
head and neck cancer.
4. Has ulceration and/or fungation of disease onto the skin surface.
5. Has a life expectancy of less than 3 months and/or has rapidly
progressing disease (eg, uncontrolled tumor pain) in the opinion of the
treating investigator.
6. Has a history of any contraindication or has a severe hypersensitivity
to any components of pembrolizumab (=Grade 3) or lenvatinib.
7. Has pre-existing =Grade 3 gastrointestinal or non-gastrointestinal
fistula.
8. Has a history of a gastrointestinal condition or procedure that, in the
opinion of the investigator, may affect oral study drug absorption.
9. Has clinically significant cardiovascular impairment within 12 months
of the first dose of study intervention.
10. Has disease that is suitable for local therapy administered with
curative intent.
11. Had PD within 6 months of completion of curatively intended
systemic treatment for locoregionally advanced HNSCC.
12. Has had major surgery within 3 weeks before first dose of study
interventions.
13. Has difficulty swallowing capsules or ingesting a suspension orally or
by a feeding tube.
14. Has received prior therapy with lenvatinib or pembrolizumab.
15. Received last dose of systemic therapy for locoregionally advanced
disease less than 6 months before signing consent
16. 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).
17. Has received prior systemic anticancer therapy including
investigational agents within 4 weeks before randomization.
18. Has received prior radiotherapy within 2 weeks of start of study
intervention.
19. Has received a live vaccine within 30 days before the first dose of
study intervention. Administration of killed vaccines is allowed.
20. Has received an investigational agent or has used an investigational
device within 4 weeks prior to study intervention.
21. Has urine protein =1 g/24 hours.
22. Has prolongation of QTc interval (calculated using Fridericia's
formula) to >480 msec.
23. Has a LVEF below the institutional (or local laboratory) normal
range, as determined by MUGA or ECHO.
24. 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 intervention.
25. Has a known additional malignancy that is progressing or has
required active treatment within the past 3 years.
26. Has known active CNS metastases and/or carcinomatous meningitis.
Participants with previously treated brain metastases may participate
provided they are radiologically stable, (ie, without evidence of
progression) for at least 4 weeks by repeat imaging (note that the
repeat imaging should be performed during study screening), clinically
stable and without requirement of steroid treatment for at least 14 days
prior to first dose of study intervention.
27. Has an active autoimmune disease that has required systemic
treatment in past 2
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