Clinical Trial Details

Efficacy and Safety of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) in Previously Treated Participants With Select Solid Tumors (MK-7902-005/E7080-G000-224/LEAP-005)

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Trial Information

Broad Health Condition Advanced Solid Tumors
Triple Negative Breast Cancer
Ovarian Cancer
Gastric Cancer
Colorectal Cancer
Glioblastoma
Biliary Tract Cancers
Pancreatic Cancer

Specific Health Condition








Trial FocusTreatment

Recruitment statusActive, not recruiting

Recruitment Details
Recruitment State
QLD,VIC,WA,

Hospital
Royal Brisbane and Women s Hospital ( Site 0901)
Sir Charles Gairdner Hospital ( Site 0903)

Phase of TrialPhase 2

Trial summary

The purpose of this study is to determine the safety and efficacy of combination therapy with
pembrolizumab (MK-3475) and lenvatinib (E7080/MK-7902) in participants with triple negative
breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (CRC), glioblastoma
(GBM), biliary tract cancers (BTC), or pancreatic cancer.
Eligibility

Key inclusion criteria

Inclusion Criteria:

    -  Has a histologically or cytologically-documented, advanced (metastatic and/or
       unresectable) solid tumor that is incurable and for which prior standard systemic
       therapy has failed in one of the following cohorts: TNBC, Ovarian Cancer, Gastric
       Cancer, Colorectal Cancer, GBM, BTC (intrahepatic, extrahepatic cholangiocarcinoma and
       gall bladder cancer; excludes Ampulla of Vater), Pancreatic Cancer

    -  Must have progressed on or since the last treatment

    -  Has measurable disease per RECIST 1.1 (RANO for the GBM cohort) as assessed by the
       local site investigator/radiology and confirmed by BICR

    -  Has provided a PD-L1 evaluable archival tumor tissue sample or newly obtained core or
       excisional biopsy of a tumor lesion not previously irradiated

    -  Male participants agree to use approved contraception during the treatment period for
       at least 7 days after the last dose of lenvatinib, or refrain from heterosexual
       intercourse during this period

    -  Female participants are not pregnant or breastfeeding, and are not a woman of
       childbearing potential (WOCBP), OR are a WOCBP that agrees to use contraception during
       the treatment period (or 14 days prior to the initiation of study treatment for oral
       contraception) and for at least 120 days post pembrolizumab, or 30 days post
       lenvatinib, whichever occurs last

    -  Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3
       days of study treatment initiation

    -  Has adequate organ function

  For Triple Negative Breast Cancer Participants:

    -  Has received one or 2 prior lines of therapy

    -  Has Lactate Dehydrogenase (LDH) <2.0 x Upper Limit of Normal (ULN)

    -  Has locally determined results for estrogen receptor, progesterone receptor, and human
       epidermal growth factor receptor 2 tumor analyses

  For Ovarian Cancer Participants:

  - Has primary ovarian cancer and has received 3 prior lines of therapy.

  For Gastric Cancer Participants:

  - Has received 2 prior lines of therapy. Note: Gastric cancer will include participants
  with both gastric and gastroesophageal junction (GEJ) adenocarcinoma. Participants with
  squamous cell carcinoma histology are not eligible

  For Colorectal Cancer Participants:

  - Has received 2 prior lines of therapy

  For GBM Participants:

    -  Has failed initial systemic therapy for newly diagnosed GBM

    -  Have the following time periods elapsed before the projected start of scheduled study
       treatment: 1) at least 3 weeks from prior surgical resection, 2) at least 1 week from
       stereotactic biopsy, 3) at least 6 months from completion of prior radiotherapy, 4) at
       least 4 weeks (or 5 half-lives, whichever is shorter) from any investigational agent,
       5) at least 4 weeks from cytotoxic therapy, 6) at least 6 weeks from antibodies, 7) at
       least 4 weeks (or 5 half-lives, whichever is shorter) from other antitumor therapies
       and 1 week for cancer vaccines

    -  Be neurologically stable (e.g. without a progression of neurologic symptoms or
       requiring escalating doses of systemic steroid therapy within last 2 weeks) and
       clinically stable

    -  Has histologically confirmed World Health Organization (WHO) Grade IV GBM

    -  Has locally determined result for O^6-methylguanine-DNA methyltransferase (MGMT)
       analysis

  For Biliary Tract Cancer Participants:

    -  Has received 1 prior line of therapy

    -  Child-Pugh Score, Class A: well-compensated disease. Child-Pugh Score of 5-6

  For Pancreatic Cancer Participants:

    -  Has pathologically (histologically or cytologically) confirmed pancreatic ductal
       adenocarcinoma that is metastatic at enrollment

    -  Has received one or 2 prior lines of therapy

    -  Has received prior therapy with at least 1 (platinum-containing regimen or
       gemcitabine-containing regimen) but no more than 2 prior systemic therapies for
       unresectable or metastatic pancreatic cancer

  Exclusion Criteria:

    -  Has gastrointestinal malabsorption or any other condition that might affect the
       absorption of lenvatinib

    -  Has present or progressive accumulation of pleural, ascitic, or pericardial fluid
       requiring drainage or diuretic drugs within 2 weeks prior to enrollment (applies to
       all cohorts except the ovarian cancer cohort)

    -  Has radiographic evidence of encasement or invasion of a major blood vessel or of
       intratumoral cavitation. Participants with portal vein invasion (Vp4), inferior vena
       cava, or cardiac involvement based on imaging in the BTC cohort are not eligible for
       enrollment

    -  Has clinical significant hemoptysis or tumor bleeding within 2 weeks prior to the
       first dose of study treatment

    -  Has significant cardiovascular impairment within 12 months of the first dose of study
       treatment, such as history of congestive heart failure greater than New York Heart
       Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular
       accident (CVA), or cardiac arrhythmia associated with hemodynamic instability

    -  Has a history of arterial thromboembolism within 12 months of start of study treatment

    -  Has a known additional malignancy that is progressing or has required active treatment
       within the past 3 years.

    -  Has a serious nonhealing wound, ulcer or bone fracture

    -  Has had major surgery within 3 weeks prior to first dose of study interventions

    -  Has biologic response modifiers therapy (e.g. granulocyte colony-stimulating factor)
       within 4 weeks before study entry

    -  Has preexisting =Grade 3 gastrointestinal (GI) or non-gastrointestinal fistula

    -  Has received prior therapy with lenvatinib, an anti-PD-1, anti-PD-L1, or anti PD-L2
       agent or with an agent directed to another stimulatory or co-inhibitory T-cell
       receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Tumor necrosis
       factor receptor superfamily, member 4 [OX 40], tumor necrosis factor receptor
       superfamily member 9 [CD137])

    -  Has received prior systemic anti-cancer therapy including investigational agents
       within 4 weeks prior to study treatment start

    -  If participant received major surgery, they must have recovered adequately from the
       toxicity and/or complications from the intervention prior to starting study treatment

    -  Has received prior radiotherapy within 2 weeks of start of study treatment.
       Participants must have recovered from all radiation-related toxicities, not require
       corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
       for palliative radiation (=2 weeks of radiotherapy) to non-central nervous system
       (CNS) disease

    -  Has received a live vaccine within 30 days prior to the first dose of study treatment

    -  Has known intolerance to lenvatinib (and/or any of the excipients)

    -  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 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 treatment

    -  Has known active CNS metastases and/or carcinomatous meningitis

    -  Has tumors involving the brain stem

    -  Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients

    -  Has an active autoimmune disease that has required systemic treatment in 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 or known active hepatitis C virus infection

    -  Has a known history of active tuberculosis (TB; Bacillus tuberculosis)

    -  Is pregnant or breastfeeding or expecting to conceive or father children within the
       projected duration of the study, starting with the screening visit through 120 days
       after the last dose of study treatment

    -  Has had an allogenic tissue/solid organ transplant (large organ transplants, stem-cell
       transplant requiring chronic immunosuppressant therapy necessary to prevent graft
       rejection)

  For GBM Participants:

    -  Has carcinomatous meningitis

    -  Has recurrent tumor greater than 6 cm in maximum diameter

    -  Has tumor primarily localized to the brainstem or spinal cord

    -  Has presence of multifocal tumor, diffuse leptomeningeal or extracranial disease

    -  Has evidence of intratumoral or peritumoral hemorrhage on baseline magnetic resonance
       imaging (MRI) scan other than those that are grade = 1 and either post-operative or
       stable on at least 2 consecutive MRI scans

    -  Has received OptuneĀ® TTFields within 2 weeks of study intervention

Minimum age18 Years

GenderAll

Can Healthy volunteers participate?No

Contact details and further information

Sponsor Primary Sponsor Type: Commercial sector/Industry
Primary Sponsor Name: Merck Sharp & Dohme Corp.

Trial websitehttps://clinicaltrials.gov/show/NCT03797326

Trial IDNCT03797326