The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03797326




Registration number
NCT03797326
Ethics application status
Date submitted
7/01/2019
Date registered
9/01/2019
Date last updated
8/08/2019

Titles & IDs
Public title
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)
Scientific title
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)
Secondary ID [1] 0 0
2018-003747-37
Secondary ID [2] 0 0
7902-005
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 0 0
Triple Negative Breast Cancer 0 0
Ovarian Cancer 0 0
Gastric Cancer 0 0
Colorectal Cancer 0 0
Glioblastoma 0 0
Biliary Tract Cancers 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Breast
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Pembrolizumab
Treatment: Drugs - Lenvatinib

Experimental: Pembrolizumab + Lenvatinib - Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) plus lenvatinib 20 mg via oral capsule once a day (QD). Pembrolizumab will be administered for up to 35 cycles (up to 2 years). Lenvatinib will be administered until progressive disease or unacceptable toxicity (up to at least 2 years).


Other interventions: Pembrolizumab
Administered as an IV infusion on Day 1 Q3W.

Treatment: Drugs: Lenvatinib
Administered orally once a day during each 21-day cycle.

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Glioblastoma (GBM) by Investigator Assessment in Initial Cohorts - ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline SOD) as assessed by the investigator per RECIST 1.1, which is modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. For participants with GBM, response will be assessed based on RANO criteria (CR: disappearance of all target lesions, PR: sum of products of diameters [SPD] decreased by = 50% from baseline value).
Timepoint [1] 0 0
Up to 18 months
Primary outcome [2] 0 0
ORR per RECIST 1.1 or RANO (GBM) by Blinded Independent Central Review (BICR) in Expanded Cohorts (Combined with Initial Cohorts) - ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) as assessed by BICR per RECIST 1.1, which is modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. For participants with GBM, response will be assessed based on RANO criteria (CR: disappearance of all target lesions, PR: SPD decreased by = 50% from baseline value).
Timepoint [2] 0 0
Up to 36 months
Primary outcome [3] 0 0
Percentage of Participants who Experience an Adverse Event (AE) - An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who experience at least one AE will be reported.
Timepoint [3] 0 0
Up to 36 months
Primary outcome [4] 0 0
Percentage of Participants who Discontinue Study Treatment Due to an Adverse Event (AE) - An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants who discontinue study treatment due to an AE will be reported.
Timepoint [4] 0 0
Up to 36 months
Secondary outcome [1] 0 0
Disease Control Rate (DCR) per RECIST 1.1 by Investigator Assessment in Initial Cohorts - DCR is defined as the percentage of participants who have a best overall response of CR, PR, or stable disease (SD) per RECIST 1.1. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and will be assessed by the investigator for this outcome measure.
Timepoint [1] 0 0
Up to 18 months
Secondary outcome [2] 0 0
Duration of Response (DOR) per RECIST 1.1 or RANO (GBM) by Investigator Assessment in Initial Cohorts - DOR is determined by disease assessment and is defined as the time from the earliest date of qualifying response until earliest date of disease progression or death from any cause, whichever comes first. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and will be assessed by the investigator for this outcome measure.
Timepoint [2] 0 0
Up to 18 months
Secondary outcome [3] 0 0
Progression Free Survival (PFS) per RECIST 1.1 or RANO (GBM) by Investigator Assessment in Initial Cohorts - PFS is defined as the time from date of study treatment to the first documented disease progression based on RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ (or RANO for GBM participants), or death due to any cause, whichever occurs first, as assessed by the investigator.
Timepoint [3] 0 0
Up to 18 months
Secondary outcome [4] 0 0
Overall Survival (OS) in Initial Cohorts - OS is defined as the time from the date of study treatment to the date of death due to any cause.
Timepoint [4] 0 0
Up to 18 months
Secondary outcome [5] 0 0
DCR per RECIST 1.1 by BICR in Expanded Cohorts (Combined with Initial Cohorts) - DCR is defined as the percentage of participants who have a best overall response of CR, PR, or (SD) per RECIST 1.1. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and will be assessed by BICR for this outcome measure.
Timepoint [5] 0 0
Up to 36 months
Secondary outcome [6] 0 0
DOR per RECIST 1.1 or RANO (GBM) by BICR in Expanded Cohorts (Combined with Initial Cohorts) - DOR is determined by disease assessment and is defined as the time from the earliest date of qualifying response until earliest date of disease progression or death from any cause, whichever comes first. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and will be assessed by BICR for this outcome measure.
Timepoint [6] 0 0
Up to 36 months
Secondary outcome [7] 0 0
PFS per RECIST 1.1 or RANO (GBM) by BICR in Expanded Cohorts (Combined with Initial Cohorts) - PFS is defined as the time from date of study treatment to the first documented disease progression based on RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ (or RANO for GBM participants), or death due to any cause, whichever occurs first, as assessed by BICR.
Timepoint [7] 0 0
Up to 36 months
Secondary outcome [8] 0 0
OS in Expanded Cohorts (Combined with Initial Cohorts) - OS is defined as the time from the date of study treatment to the date of death due to any cause.
Timepoint [8] 0 0
Up to 36 months
Secondary outcome [9] 0 0
Plasma Concentration of Lenvatinib - Blood samples will be obtained on Day 1 and Day 15 of Cycle 1 (21-day cycle) and Day 1 of Cycle 2 (21-day cycle) for pharmacokinetic (PK) analysis to determine the plasma concentration of lenvatinib.
Timepoint [9] 0 0
Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose and 2-12 hours post-dose; Cycle 2 Day 1: pre-dose, 0.5-4 hours, and 6-10 hours post-dose (up to approximately 23 days). Each cycle is 21 days.

Eligibility
Key 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 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 30 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 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)

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

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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Has presence of gastrointestinal condition including malabsorption that might affect
the absorption of lenvatinib

- Has radiographic evidence of major blood vessel invasion/infiltration

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

- Serious nonhealing wound, ulcer or bone fracture

- Has biologic response modifiers (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 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

- 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 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

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

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 0 0
Royal Brisbane and Women s Hospital ( Site 0901) - Herston
Recruitment hospital [2] 0 0
Alfred Health ( Site 0902) - Melbourne
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
New Jersey
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Tennessee
Country [6] 0 0
United States of America
State/province [6] 0 0
Washington
Country [7] 0 0
United States of America
State/province [7] 0 0
Wisconsin
Country [8] 0 0
Canada
State/province [8] 0 0
Manitoba
Country [9] 0 0
Canada
State/province [9] 0 0
Ontario
Country [10] 0 0
Canada
State/province [10] 0 0
Quebec
Country [11] 0 0
Chile
State/province [11] 0 0
Santiago
Country [12] 0 0
Chile
State/province [12] 0 0
Temuco
Country [13] 0 0
France
State/province [13] 0 0
Lille
Country [14] 0 0
France
State/province [14] 0 0
Lyon
Country [15] 0 0
France
State/province [15] 0 0
Nice
Country [16] 0 0
France
State/province [16] 0 0
Saint-Herblain
Country [17] 0 0
France
State/province [17] 0 0
Toulouse
Country [18] 0 0
France
State/province [18] 0 0
Villejuif
Country [19] 0 0
Germany
State/province [19] 0 0
Frankfurt am Main
Country [20] 0 0
Germany
State/province [20] 0 0
Jena
Country [21] 0 0
Germany
State/province [21] 0 0
Regensburg
Country [22] 0 0
Germany
State/province [22] 0 0
Wiesbaden
Country [23] 0 0
Israel
State/province [23] 0 0
Beer Sheva
Country [24] 0 0
Israel
State/province [24] 0 0
Haifa
Country [25] 0 0
Israel
State/province [25] 0 0
Ramat Gan
Country [26] 0 0
Israel
State/province [26] 0 0
Tel Aviv
Country [27] 0 0
Korea, Republic of
State/province [27] 0 0
Seoul
Country [28] 0 0
Spain
State/province [28] 0 0
Barcelona
Country [29] 0 0
Spain
State/province [29] 0 0
Madrid
Country [30] 0 0
United Kingdom
State/province [30] 0 0
Cambridgeshire
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Leicester
Country [32] 0 0
United Kingdom
State/province [32] 0 0
London
Country [33] 0 0
United Kingdom
State/province [33] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Eisai Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief 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), or biliary tract cancers (BTC). Participants will be enrolled into initial
tumor-specific cohorts which will be expanded if adequate efficacy is determined.
Trial website
https://clinicaltrials.gov/show/NCT03797326
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@merck.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03797326