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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03797326
Ethics application status
Date submitted
7/01/2019
Date registered
9/01/2019

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
MK-7902-005
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
Pancreatic Cancer 0 0
Condition category
Condition code
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
Treatment: Other - Pembrolizumab
Treatment: Drugs - Lenvatinib

Experimental: Pembrolizumab + Lenvatinib (Arm 1) - 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).

Experimental: Lenvatinib Monotherapy (Arm 2) - Participants receive lenvatinib 24 mg via oral capsule QD, to be administered until progressive disease or unacceptable toxicity (up to at least 2 years).


Treatment: Other: 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
Treatment: Other
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
Timepoint [1] 0 0
Up to approximately 72 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)
Timepoint [2] 0 0
Up to approximately 72 months
Primary outcome [3] 0 0
Percentage of Participants Receiving Pembrolizumab Plus Lenvatinib who Experience an Adverse Event (AE)
Timepoint [3] 0 0
Up to approximately 72 months
Primary outcome [4] 0 0
Percentage of Participants Receiving Pembrolizumab Plus Lenvatinib who Discontinue Study Treatment Due to an AE
Timepoint [4] 0 0
Up to approximately 72 months
Primary outcome [5] 0 0
Percentage of Participants Receiving Lenvatinib Monotherapy who Experience an AE
Timepoint [5] 0 0
Up to approximately 72 months
Primary outcome [6] 0 0
Percentage of Participants Receiving Lenvatinib Monotherapy who Discontinue Study Treatment Due to an Adverse Event (AE)
Timepoint [6] 0 0
Up to approximately 72 months
Secondary outcome [1] 0 0
Disease Control Rate (DCR) per RECIST 1.1 by Investigator Assessment in Initial Cohorts
Timepoint [1] 0 0
Up to approximately 72 months
Secondary outcome [2] 0 0
Duration of Response (DOR) per RECIST 1.1 or RANO (GBM) by Investigator Assessment in Initial Cohorts
Timepoint [2] 0 0
Up to approximately 72 months
Secondary outcome [3] 0 0
Progression Free Survival (PFS) per RECIST 1.1 or RANO (GBM) by Investigator Assessment in Initial Cohorts
Timepoint [3] 0 0
Up to approximately 72 months
Secondary outcome [4] 0 0
Overall Survival (OS) in Initial Cohorts
Timepoint [4] 0 0
Up to approximately 72 months
Secondary outcome [5] 0 0
DCR per RECIST 1.1 by BICR in Expanded Cohorts (Combined with Initial Cohorts)
Timepoint [5] 0 0
Up to approximately 72 months
Secondary outcome [6] 0 0
DOR per RECIST 1.1 or RANO (GBM) by BICR in Expanded Cohorts (Combined with Initial Cohorts)
Timepoint [6] 0 0
Up to approximately 72 months
Secondary outcome [7] 0 0
PFS per RECIST 1.1 or RANO (GBM) by BICR in Expanded Cohorts (Combined with Initial Cohorts)
Timepoint [7] 0 0
Up to approximately 72 months
Secondary outcome [8] 0 0
OS in Expanded Cohorts (Combined with Initial Cohorts)
Timepoint [8] 0 0
Up to approximately 72 months
Secondary outcome [9] 0 0
ORR per RECIST 1.1 by BICR in Lenvatinib Monotherapy Arm
Timepoint [9] 0 0
Up to approximately 72 months
Secondary outcome [10] 0 0
DCR per RECIST 1.1 by BICR in Lenvatinib Monotherapy Arm
Timepoint [10] 0 0
Up to approximately 72 months
Secondary outcome [11] 0 0
DOR per RECIST 1.1 by BICR in Lenvatinib Monotherapy Arm
Timepoint [11] 0 0
Up to approximately 72 months
Secondary outcome [12] 0 0
PFS per RECIST 1.1 by BICR in Lenvatinib Monotherapy Arm
Timepoint [12] 0 0
Up to approximately 72 months
Secondary outcome [13] 0 0
OS in Lenvatinib Monotherapy Arm
Timepoint [13] 0 0
Up to approximately 72 months
Secondary outcome [14] 0 0
Plasma Concentration of Lenvatinib
Timepoint [14] 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, 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 Optune® TTFields within 2 weeks of study intervention

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
12/02/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
28/10/2024
Sample size
Target
Accrual to date
Final
603
Recruitment in Australia
Recruitment state(s)
QLD,VIC,WA
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 hospital [3] 0 0
Sir Charles Gairdner Hospital ( Site 0903) - Nedlands
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
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
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
New Jersey
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Dakota
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
South Dakota
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Washington
Country [12] 0 0
United States of America
State/province [12] 0 0
Wisconsin
Country [13] 0 0
Argentina
State/province [13] 0 0
Buenos Aires
Country [14] 0 0
Argentina
State/province [14] 0 0
Caba
Country [15] 0 0
Argentina
State/province [15] 0 0
Santa Fe
Country [16] 0 0
Canada
State/province [16] 0 0
British Columbia
Country [17] 0 0
Canada
State/province [17] 0 0
Manitoba
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
Chile
State/province [20] 0 0
Araucania
Country [21] 0 0
Chile
State/province [21] 0 0
Region M. De Santiago
Country [22] 0 0
Colombia
State/province [22] 0 0
Antioquia
Country [23] 0 0
Colombia
State/province [23] 0 0
Distrito Capital De Bogota
Country [24] 0 0
Colombia
State/province [24] 0 0
Risaralda
Country [25] 0 0
Colombia
State/province [25] 0 0
Valle Del Cauca
Country [26] 0 0
France
State/province [26] 0 0
Alpes-Maritimes
Country [27] 0 0
France
State/province [27] 0 0
Auvergne
Country [28] 0 0
France
State/province [28] 0 0
Haute-Garonne
Country [29] 0 0
France
State/province [29] 0 0
Nord
Country [30] 0 0
France
State/province [30] 0 0
Val-de-Marne
Country [31] 0 0
Germany
State/province [31] 0 0
Baden-Wurttemberg
Country [32] 0 0
Germany
State/province [32] 0 0
Bayern
Country [33] 0 0
Germany
State/province [33] 0 0
Hessen
Country [34] 0 0
Germany
State/province [34] 0 0
Thuringen
Country [35] 0 0
Israel
State/province [35] 0 0
Beer Sheva
Country [36] 0 0
Israel
State/province [36] 0 0
Haifa
Country [37] 0 0
Israel
State/province [37] 0 0
Jerusalem
Country [38] 0 0
Israel
State/province [38] 0 0
Ramat Gan
Country [39] 0 0
Israel
State/province [39] 0 0
Tel Aviv
Country [40] 0 0
Italy
State/province [40] 0 0
Milano
Country [41] 0 0
Italy
State/province [41] 0 0
Toscana
Country [42] 0 0
Italy
State/province [42] 0 0
Napoli
Country [43] 0 0
Italy
State/province [43] 0 0
Roma
Country [44] 0 0
Korea, Republic of
State/province [44] 0 0
Seoul
Country [45] 0 0
Russian Federation
State/province [45] 0 0
Arkhangel Skaya Oblast
Country [46] 0 0
Russian Federation
State/province [46] 0 0
Moskva
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Sankt-Peterburg
Country [48] 0 0
Russian Federation
State/province [48] 0 0
Tatarstan, Respublika
Country [49] 0 0
Spain
State/province [49] 0 0
Barcelona
Country [50] 0 0
Spain
State/province [50] 0 0
Madrid
Country [51] 0 0
Switzerland
State/province [51] 0 0
Berne
Country [52] 0 0
Switzerland
State/province [52] 0 0
Grisons
Country [53] 0 0
Switzerland
State/province [53] 0 0
Sankt Gallen
Country [54] 0 0
Switzerland
State/province [54] 0 0
Ticino
Country [55] 0 0
Switzerland
State/province [55] 0 0
Geneve
Country [56] 0 0
Switzerland
State/province [56] 0 0
Zurich
Country [57] 0 0
Taiwan
State/province [57] 0 0
Tainan
Country [58] 0 0
Taiwan
State/province [58] 0 0
Taipei
Country [59] 0 0
Thailand
State/province [59] 0 0
Krung Thep Maha Nakhon
Country [60] 0 0
United Kingdom
State/province [60] 0 0
Cambridgeshire
Country [61] 0 0
United Kingdom
State/province [61] 0 0
Leicestershire
Country [62] 0 0
United Kingdom
State/province [62] 0 0
London, City Of
Country [63] 0 0
United Kingdom
State/province [63] 0 0
Surrey
Country [64] 0 0
United Kingdom
State/province [64] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
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
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents



Results not provided in https://clinicaltrials.gov/study/NCT03797326