Multizentrische, offene Phase-II-Studie zu Lenvatinib (E7080/MK-7902) plus Pembrolizumab (MK-3475) bei vorbehandelten Personen mit ausgewählten soliden Tumoren (LEAP-005)

Biological: Pembrolizumab;Drug: Lenvatinib

Gender: All
Maximum age: N/A
Minimum age: 18 Years

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