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)

Conditions:Breast Cancer, Colorectal Cancer, Ovarian Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Cancer, Brain Cancer
Therapuetic Areas:Oncology
Age Range:18 - Any
Start Date:February 12, 2019
End Date:April 11, 2022
Contact:Toll Free Number

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A Multicenter, Open-label Phase 2 Study of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) in Previously Treated Subjects With Selected Solid Tumors (LEAP-005)

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), or biliary tract cancers (BTC). Participants will be enrolled into initial
tumor-specific cohorts which will be expanded if adequate efficacy is determined.

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: non-microsatellite instability-High/proficient mismatch
repair (MSI-H/pMMR) tumor, GBM, BTC: intrahepatic, extrahepatic cholangiocarcinoma and
gall bladder cancer; excludes Ampulla of Vater

- 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 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 and
for at least 120 days after the last dose of study treatment, and refrain from
donating sperm 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 after the last dose of study treatment

- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 7
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)

For Ovarian Cancer Participants:

- Has received 3 prior lines of therapy

For Gastric Cancer Participants:

- Has received 2 prior lines of therapy

For Colorectal Cancer Participants:

- Has received 2 prior lines of therapy

- Has a locally determined non-MSI-H/pMMR tumor

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

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

Exclusion Criteria:

- Has presence of gastrointestinal condition including malabsorption that might affect
the absorption of lenvatinib

- Radiographic evidence of major blood vessel invasion/infiltration

- 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.

- Serious nonhealing wound, ulcer or bone fracture

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

- 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 or 5 times the half-life time, whichever is shorter 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

- Known intolerance to study treatment (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

- 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

For Colorectal Cancer Participants:

- Has MSI-H/dMMR disease

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
We found this trial at
Duarte, California 91010
Phone: 626-218-9200
Duarte, CA
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Herston, Queensland 4029
Phone: +61736468111
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600 Highland Ave.
Madison, Wisconsin 53792
(608) 263-6400
Phone: 608-262-5223
University of Wisconsin Carbone Cancer Center UW Carbone Cancer Center holds the unique distinction of...
Madison, WI
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