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AzTrials

TumorsPhase 1/2NCT02501096

A Trial of Lenvatinib (E7080) Plus Pembrolizumab in Participants With Selected Solid Tumors

A Phase 1/2 study testing Lenvatinib and Pembrolizumab in people with Tumors, run by Eisai Inc. at 64 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is an open-label Phase 1b/2 trial of lenvatinib (E7080) plus pembrolizumab in participants with selected solid tumors. Phase 1b will determine and confirm the maximum tolerated dose (MTD) for lenvatinib in combination with 200 milligrams (mg) (intravenous [IV], every 3 weeks [Q3W]) pembrolizumab in participants… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Tumors
What is being tested?
Lenvatinib and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
357 participants
Where
64 sitesin 3 countries
Study dates
22 Jul 2015to 11 Jul 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Phase 1b: Histologically and/or cytologically confirmed metastatic selected solid tumor types that have progressed after treatment with approved therapies or for which there are no standard effective therapies available. If nivolumab or pembrolizumab is an approved therapy for the participant's tumor type, but the participant has not been treated with it, the Investigator may enroll the participant in this study.
  • Phase 2: Histologically and/or cytologically confirmed metastatic selected solid tumor types with 0-2 prior lines of systemic therapy. If previously treated, participant has progressed after previous treatment. For the non-small cell lung cancer (NSCLC) and melanoma cohorts, participants must have progressed on or after prior treatment with one anti-programmed cell death protein 1 (anti-PD-1), anti-PD-1 ligand 1 (anti-PD-L1), or anti-PD-1 ligand 2 (anti-PD-L2) agent. For the renal cell carcinoma (RCC) cohort, participants must have progressed on treatment with an anti- programmed death receptor-1 /programmed death receptor-ligand 1 monoclonal antibody (anti-PD-1/PD-L1 mAb) administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies, the regimen with an anti-PD-1/PD-L1 mAb must be the most recent therapy. Selected tumor types of both phases: NSCLC, predominantly clear cell renal cell carcinoma, endometrial carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, or melanoma (excluding uveal melanoma)
  • Life expectancy of 12 weeks or more
  • Phase 2: Measurable disease meeting the following criteria:
  • At least 1 lesion of greater than or equal to 10 mm in the longest diameter for a non-lymph node or greater than or equal to 15 mm in the short-axis diameter for a lymph node that is serially measurable according to irRECIST (immune-related Response Evaluation Criteria in Solid Tumors) using computerized tomography/magnetic resonance imaging (CT/MRI)
  • Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation must show subsequent evidence of substantial size increase to be deemed a target lesion
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  • Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
  • Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than or equal to 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Cycle 1 Day 1
  • Adequate renal function defined as creatinine less than or equal to 1.5*ULN (upper limit of normal) or calculated creatinine clearance greater than or equal to 40 mL/min per the Cockcroft and Gault formula with creatinine levels greater than 1.5*ULN
  • Adequate bone marrow function:
  • Absolute neutrophil count (ANC) greater than or equal to 1500/mm3 (greater than or equal to 1.5 X 103/uL)
  • Platelets greater than or equal to 100,000/mm3 (greater than or equal to 100 X 109/L)
  • Hemoglobin greater than or equal to 9.0 g/dL
  • Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) less than or equal to 1.5
  • Adequate liver function as evidenced by bilirubin less than or equal to 1.5 times the ULN and alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) less than or equal to 3*ULN (in the case of liver metastases less than or equal to 5*ULN). In case ALP is greater than 3 X ULN (in the absence of liver metastases) or greater than 5 X ULN (in the presence of liver metastases) AND the participant also is known to have bone metastases, the liver specific ALP must be separated from the total and used to assess the liver function instead of the total ALP
  • Males or females age greater than or equal to 18 years at the time of informed consent
  • Participants with known brain metastases will be eligible if they have completed the primary brain therapy (such as whole brain radiotherapy, stereotactic radiosurgery or complete surgical resection) and if they have remained clinically stable, asymptomatic and off of steroids for at least 28 days before starting study treatment.
  • All females must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of beta-human chorionic gonadotropin [β-hCG]) at the Screening Visit and the Baseline Visit. A pregnancy test needs to be performed within 72 hours of the first dose of study drug. Females of childbearing potential must agree to use a highly effective method of contraception for the entire study period and for 120 days after study discontinuation, ie
  • total abstinence (if it is their preferred and usual lifestyle)
  • an intrauterine device (IUD) or hormone-releasing system (IUS)
  • a contraceptive implant
  • an oral contraceptive** (with additional barrier method) OR
  • have a vasectomized partner with confirmed azoospermia.
  • NOTES:
  • All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing).
  • Must be on a stable dose of the same oral hormonal contraceptive product for at least 4 weeks before dosing with study drug and for the duration of the study
  • Male participants who are partners of women of childbearing potential must use a condom + spermicide and their female partners if of childbearing potential must use a highly effective method of contraception (see methods described in Inclusion Criterion #12) beginning at least 1 menstrual cycle prior to starting study drug(s), throughout the entire study period, and for 120 days after the last dose of study drug, unless the male participants are totally sexually abstinent or have undergone a successful vasectomy with confirmed azoospermia or unless the female partners have been sterilized surgically or are otherwise proven sterile.
  • Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol
  • Archival tumor tissue or a newly obtained biopsy must be available prior to the first dose of study drug for biomarker analysis. In the case archival tissue cannot be provided, participants with inaccessible tumors for biopsy specimens can be enrolled without a biopsy upon consultation and agreement by the sponsor Note: In case of submitting unstained cut slides, freshly cut slides should be submitted to the testing laboratory within 14 days from when the slides are cut.

Who cannot join

  • Prior anticancer treatment within 28 days (or 5 times the half-life time, whichever is shorter) or any investigational agent within 30 days prior to the first dose of study drugs. All acute toxicities related to prior treatments must be resolved to Grade less than or equal to 1
  • Participants must have recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy
  • Participants having greater than 1+ proteinuria on urinalysis will undergo 24-h urine collection for quantitative assessment of proteinuria. Participants with urine protein greater than or equal to 1 g/24-hour will be ineligible.
  • Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
  • New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months
  • Prolongation of corrected QT (QTc) interval to greater than 480 msec
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  • Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug
  • Active infection (any infection requiring systemic treatment)
  • Participant is known to be positive for Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C
  • Serious nonhealing wound, ulcer, or bone fracture
  • Known intolerance to either of the study drugs (or any of the excipients)
  • History of organ allograft (Participant has had an allogenic tissue/solid organ transplant)
  • Biologic response modifiers (eg, granulocyte colony-stimulating factor) within 4 weeks before study entry. Chronic erythropoietin therapy is permitted provided that no dose adjustments were made within 2 months before first dose of study treatment
  • Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial
  • Females who are pregnant or breastfeeding
  • Excluding the primary tumor leading to enrollment in this study, any other active malignancy (except for definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the bladder or cervix) within the past 24 months
  • Prior treatment with lenvatinib or any PD-1, anti-PD-L1, or anti-PD-L2 agent, excluding melanoma and NSCLC where prior treatment with one PD-1, anti-PD-L1, or anti-PD-L2 agent is allowed, and excluding RCC where prior treatment with one regimen containing an anti-PD-1/PD-L1 mAb is required.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. The use of physiologic doses of corticosteroids (up to 7.5mg/d of prednisone or equivalent) may be approved after consultation with the sponsor.
  • No active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Has received a live-virus vaccination within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted.

Trial locations and contacts

64 sites in 3 countries.

64 sites in 3 countries

United States50 sites

  • New York Hematology Oncology (US Onc)

    Albany, New York

  • Alaska Clinical Research Center

    Anchorage, Alaska

  • Piedmont Cancer Institue

    Atlanta, Georgia

  • Rocky Mountain Cancer Centers

    Aurora, Colorado

  • Texas Oncology-Bedford

    Bedford, Texas

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts

  • Mass General Hospital

    Boston, Massachusetts

  • Rocky Mountain Cancer Centers

    Boulder, Colorado

  • The University of Chicago

    Chicago, Illinois

  • Rocky Mountain Cancer Centers

    Colorado Springs, Colorado

  • Texas Oncology (US Onc)

    Dallas, Texas

  • Texas Oncology

    Dallas, Texas

  • Texas Oncology-Denton South

    Denton, Texas

  • Rocky Mountain Cancer Centers, Site #1

    Denver, Colorado

  • Rocky Mountain Cancer Centers, Site #2

    Denver, Colorado

  • Texas Oncology-Fort Worth, Site #1

    Fort Worth, Texas

  • Texas Oncology-Grapevine

    Grapevine, Texas

  • Memorial Sloan Kettering at Westchester

    Harrison, New York

  • Comprehensive Cancer Centers of Nevada, Site #1

    Henderson, Nevada

  • Comprehensive Cancer Centers of Nevada, Site #2

    Henderson, Nevada

  • Comprehensive Cancer Centers of Nevada, Site #3

    Henderson, Nevada

  • Rocky Mountain Cancer Centers

    Lakewood, Colorado

  • Comprehensive Cancer Centers of Nevada, Site #1

    Las Vegas, Nevada

  • Comprehensive Cancer Centers of Nevada, Site #2

    Las Vegas, Nevada

  • Comprehensive Cancer Centers of Nevada, Site #3

    Las Vegas, Nevada

  • Comprehensive Cancer Centers of Nevada, Site #4

    Las Vegas, Nevada

  • Rocky Mountain Cancer Centers

    Littleton, Colorado

  • Rocky Mountain Cancer Centers

    Lone Tree, Colorado

  • Rocky Mountain Cancer Centers

    Longmont, Colorado

  • Texas Oncology-Longview Cancer Center

    Longview, Texas

  • Baptist Health Medical Group Oncology, LLC, Site #1

    Miami, Florida

  • Baptist Health Medical Group Oncology, LLC, Site #2

    Miami, Florida

  • Baptist Health Medical Group Oncology, LLC, Site #3

    Miami, Florida

  • University of Minnesota, Masonic Cancer Center

    Minneapolis, Minnesota

  • Memorial Sloan Kettering Cancer Center

    New York, New York

  • Arizona Oncology Associates

    Oro Valley, Arizona

  • Rocky Mountain Cancer Centers

    Parker, Colorado

  • University of Pennsylvania

    Philadelphia, Pennsylvania

  • Texas Oncology-Plano West

    Plano, Texas

  • Boca Raton Clinical Research Medical Center

    Plantation, Florida

  • Oregon Health & Science University

    Portland, Oregon

  • Rocky Mountain Cancer Centers

    Pueblo, Colorado

  • South Texas Accelerated Research Therapeutics, LLC

    San Antonio, Texas

  • Rocky Mountain Cancer Centers

    Thornton, Colorado

  • Arizona Oncology Associates, PC - HOPE, Site #1

    Tucson, Arizona

  • Arizona Oncology Associates, PC - HOPE, Site #2

    Tucson, Arizona

  • Arizona Oncology Associates, PC - HOPE, Site #3

    Tucson, Arizona

  • Texas Oncology-Tyler

    Tyler, Texas

  • Texas Oncology-Waco, Site #1

    Waco, Texas

  • Texas Oncology-Waco, Site #2

    Waco, Texas

Other trials in United States

Spain9 sites

  • Hospital Universitari Germans Trias i Pujol

    Badalona

  • Hospital Universitari Vall d'Hebron

    Barcelona

  • Hospital Universitario De Fuenlabrada

    Fuenlabrada

  • Hospital La Paz

    Madrid

  • Hospital Universitario Clinico San Carlos

    Madrid

  • MD Anderson Cancer Center Madrid - España

    Madrid

  • Parc Taulí Sabadell

    Sabadell

  • Hospital Virgen de la Salud

    Toledo

  • Hospital Universitari i Politécnic La Fe.

    Valencia

Other trials in Spain

Norway5 sites

  • Haukeland Univerity Hospital

    Bergen

  • Sørlandet Hospital

    Kristiansand, 4604

  • Akershus Universitetssykehus HF

    Lørenskog

  • Oslo Univerity Hospital

    Oslo

  • Sykehuset Østfold

    Sarpsborg

Other trials in Norway

About this study

Official title: A Multicenter, Open-Label Phase 1b/2 Trial of Lenvatinib (E7080) Plus Pembrolizumab in Subjects With Selected Solid Tumors

This is an open-label Phase 1b/2 trial of lenvatinib (E7080) plus pembrolizumab in participants with selected solid tumors. Phase 1b will determine and confirm the maximum tolerated dose (MTD) for lenvatinib in combination with 200 milligrams (mg) (intravenous [IV], every 3 weeks [Q3W]) pembrolizumab in participants with selected solid tumors (i.e. non-small cell lung cancer, renal cell carcinoma, endometrial carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, melanoma or leiomyosarcoma). Phase 2 (Expansion) will evaluate the safety and efficacy of the combination in 7 cohorts at the MTD from Phase 1b (lenvatinib 20 mg/day orally + pembrolizumab 200 mg Q3W, IV).

Conditions
Tumors
Keywords
Lenvatinib, Lenvima, E7080, Phase 1b/2, Pembrolizumab, Keytruda, Solid tumors
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LenvatinibDrug

    Also called Lenvima, E7080

    Lenvatinib will be administered with water orally once a day (with or without food) continuously in 21-day treatment cycle.

  • PembrolizumabDrug

    Also called Keytruda, MK-3475

    Pembrolizumab will be administered as a dose of 200 mg Q3W, IV in 21-day treatment cycle.

Study groups in NCT02501096
Study groupRoleWhat they receive
Lenvatinib + PembrolizumabExperimentalParticipants with one of the tumors: non-small cell lung cancer, renal cell carcinoma, endometrial cancer, urothelial cancer, squamous cell carcinoma of the head and neck, melanoma or leiomyosarcoma.
Receives: Drug: Lenvatinib; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1b: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Lenvatinib

    MTD was confirmed if no more than 3 participants experience dose-limiting toxicities(DLTs)during first 3 weeks (Cycle 1) of treatment.If MTD was not confirmed at dose level,then enrollment was proceeded to next lower dose level.Sponsor and investigators reviewed all participants' safety;clinical data to jointly determine RP2D of combination of treatment.DLT may be any of following: hematological/nonhematological toxicities considered to be at least possibly related to Lenvatinib/pembrolizumab occurring during Cycle 1;Failure to administer greater than or equal to (>=) 75 percent (%) of planned dosage of lenvatinib as result of treatment-related toxicity during Cycle 1;Who discontinue treatment due to treatment-related toxicity.Greater than 2 week delay in starting Cycle 2 because of treatment-related toxicity,even if toxicity does not meet DLT criteria.Toxicity was evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03(NCI CTCAE v 4.03).

    Measured: Cycle 1 (21 days)

  2. Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs) of Lenvatinib

    A DLT was defined as any of the following: any of the hematological or nonhematological toxicities considered to be at least possibly related to lenvatinib and/or pembrolizumab occurring during Cycle 1. Failure to administer >=75% of the planned dosage of lenvatinib as a result of treatment-related toxicity during Cycle 1. Participants who discontinue treatment due to treatment-related toxicity. Greater than 2 week delay in starting Cycle 2 because of a treatment-related toxicity, even if the toxicity does not meet DLT criteria. Toxicity was evaluated as per NCI CTCAE v 4.03.

    Measured: Cycle 1 (21 days)

  3. Objective Response Rate (ORR) Based on Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) Version 1.1 at Week 24

    ORR was defined as the percentage of participants whose best overall response (BOR) was immune related complete response (irCR) or immune related partial response (irPR) based on investigator assessment according to irRECIST version 1.1. irCR was defined as disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (<) 10 millimeter (mm). irPR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum of diameters.

    Measured: Week 24

Secondary outcomes (10)

  1. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

    TEAE: adverse event (AE) emerged during treatment, having been absent at pretreatment or reemerged during treatment, present at pretreatment but stopped before treatment or worsened in severity during treatment relative to pretreatment state, when AE is continuous. AE: any untoward medical occurrence in participant administered an investigational product. TEAEs were based on participants laboratory tests, regular measurement of vital signs, echocardiograms/multigated acquisition scans to assess left ventricular ejection fraction and electrocardiograms parameter values. TESAE: any untoward medical occurrence that at any dose: resulted in death; life threatening condition; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; a congenital anomaly/birth defect or was medically important due to reasons other than above criteria.

    Measured: From date of first dose up to 30 days after the last dose of study drugs (Up to 74 months)

  2. Objective Response Rate (ORR) Based on irRECIST Version 1.1

    ORR was defined as the percentage of participants whose BOR was irCR or irPR according to irRECIST version 1.1. irCR was defined as disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to <10 mm. irPR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum of diameters.

    Measured: From date of first dose of study drug administration until immune related (irPD), development of unacceptable toxicity, participant choice, withdrawal of consent, lost to follow up or discontinuation of this study by the sponsor (up to 73 months)

  3. Progression-free Survival (PFS) Based on irRECIST Version 1.1

    PFS was defined as the time from the first dose date to the date of irPD or date of death (whichever occurred first) according to irRECIST version 1.1. irPD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that was the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions was also considered progression).

    Measured: From date of first dose of study drug administration to date of irPD or date of death, whichever occurred first (up to 73 months)

  4. Overall Survival (OS)

    OS was defined as the time from the first dose date to the date of death from any cause.

    Measured: From the first dose until death from any cause, up to 73 months

  5. Disease Control Rate (DCR) Based on irRECIST Version 1.1

    DCR: percentage of participants with a confirmed irCR, irPR, or ir-stable disease (SD) (duration of irSD greater than or equal to [>=] 5 weeks). DCR was assessed on irRECIST v1.1. irCR: disappearance of all target lesions. All pathological lymph nodes (whether target or non-target) must have reduction in their short axis to <10 mm. irPR: at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference baseline sum of longest diameter. irSD: neither sufficient shrinkage to qualify for irPR nor sufficient increase to qualify for irPD, taking as reference smallest sum diameters while on study. irPD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (this includes baseline sum if that is the smallest on study).

    Measured: From first dose of the study drug until irPD, development of unacceptable toxicity, participant choice, withdrawal of consent, lost to follow up or discontinuation of this study by the sponsor (up to 73 months)

  6. Clinical Benefit Rate (CBR) Based on irRECIST Version 1.1

    CBR was defined as the percentage of participants with BOR of irCR or irPR or irdurable stable disease (irdSD) (duration of irSD >=23 weeks) [irCR + irPR + irdSD] based on irRECIST v1.1. irCR: disappearance of all target lesions. All pathological lymph nodes (whether target or non-target) must have reduction in their short axis to <10 mm. irPR: at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference baseline sum of longest diameter. irSD: neither sufficient shrinkage to qualify for irPR nor sufficient increase to qualify for irPD, taking as reference smallest sum diameters while on study. irPD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (this includes baseline sum if that is the smallest on study).

    Measured: From first dose date until irPD, development of unacceptable toxicity, participant choice, withdrawal of consent, lost to follow up or discontinuation of this study by the sponsor (up to 73 months)

  7. Durable Stable Disease Rate (DSDR) Based on irRECIST Version 1.1

    Durable SD rate is defined as the percentage of participants whose observed BOR is irSD and the duration of irSD is >=23 weeks based on irRECIST v1.1.

    Measured: From first dose date until irPD, development of unacceptable toxicity, participant choice, withdrawal of consent, lost to follow up or discontinuation of this study by the sponsor (up to 73 months)

  8. Duration of Objective Response (DOR) Based on irRECIST Version 1.1

    DOR: time from date of first observation of response (irPR or irCR) to date of the first observation of progression based on irRECIST 1.1, or date of death, whatever the cause. irCR: disappearance of all target and non-target lesions. All pathological (whether target or non-target) must have reduction in their short axis <10 mm. irPR: at least 30% decrease in sum of diameter (SOD) of target lesions, taking as reference baseline sum diameters. irPD was defined as at least 20% increase (including an absolute increase of at least 5 mm) in SOD of target lesions, taking as reference smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.

    Measured: First documentation of irCR or irPR until first documentation of progression or death (up to 73 months)

  9. Phase 1b: Plasma Concentrations of Lenvatinib

    Observed plasma concentration of Lenvatinib was reported here quantified by liquid chromatography with tandem mass spectrometry (LCMS/MS) method.

    Measured: Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post dose; Cycle 1 Day 15: predose, 0.5-4 hours and 6-10 hours post dose, Cycle 2 Day 1: predose, 2-12 hour postdose and Cycles 3,4,5,6 Day 1 predose (Cycle length =21 days)

  10. Plasma Concentrations of Lenvatinib

    Observed plasma concentration of Lenvatinib was reported here quantified by LCMS/MS method.

    Measured: Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post dose; Cycle 1 Day 15: predose, 0.5-4 hours and 6-10 hours post dose, Cycle 2 Day 1: predose, 2-12 hour postdose and Cycles 3,4,5,6 Day 1 predose (Cycle length =21 days):

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jul 2015 (estimated)
  2. Study start22 Jul 2015
  3. Primary completion18 Aug 2020
  4. Study completion11 Jul 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
357 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02501096
Sponsor's protocol ID
E7080-A001-111
Other IDs
2017-000300-26, 2017
Status last verified
Jun 2022
First submitted
15 Jul 2015
Last updated
20 Jul 2023
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Makker V, Taylor MH, Aghajanian C, Cohn AL, Brose MS, Simone CD, Cao ZA, Suttner L, Loboda A, Cristescu R, Jelinic P, Orlowski R, Dutta L, Matsui J, Dutcus CE, Minoshima Y, Messing MJ. Evaluation of potential biomarkers for lenvatinib plus pembrolizumab among patients with advanced endometrial cancer: results from Study 111/KEYNOTE-146. J Immunother Cancer. 2024 Jan 19;12(1):e007929. doi: 10.1136/jitc-2023-007929.

    PubMed 38242717

  • Makker V, Aghajanian C, Cohn AL, Romeo M, Bratos R, Brose MS, Messing M, Dutta L, Dutcus CE, Huang J, Schmidt EV, Orlowski R, Taylor MH. A Phase Ib/II Study of Lenvatinib and Pembrolizumab in Advanced Endometrial Carcinoma (Study 111/KEYNOTE-146): Long-Term Efficacy and Safety Update. J Clin Oncol. 2023 Feb 10;41(5):974-979. doi: 10.1200/JCO.22.01021. Epub 2023 Jan 6.

    PubMed 36608305

  • Lee CH, Shah AY, Rasco D, Rao A, Taylor MH, Di Simone C, Hsieh JJ, Pinto A, Shaffer DR, Girones Sarrio R, Cohn AL, Vogelzang NJ, Bilen MA, Gunnestad Ribe S, Goksel M, Tennoe OK, Richards D, Sweis RF, Courtright J, Heinrich D, Jain S, Wu J, Schmidt EV, Perini RF, Kubiak P, Okpara CE, Smith AD, Motzer RJ. Lenvatinib plus pembrolizumab in patients with either treatment-naive or previously treated metastatic renal cell carcinoma (Study 111/KEYNOTE-146): a phase 1b/2 study. Lancet Oncol. 2021 Jul;22(7):946-958. doi: 10.1016/S1470-2045(21)00241-2. Epub 2021 Jun 15.

    PubMed 34143969

  • Lee CH, DiNatale RG, Chowell D, Krishna C, Makarov V, Valero C, Vuong L, Lee M, Weiss K, Hoen D, Morris L, Reznik E, Murray S, Kotecha R, Voss MH, Carlo MI, Feldman D, Sachdev P, Adachi Y, Minoshima Y, Matsui J, Funahashi Y, Nomoto K, Hakimi AA, Motzer RJ, Chan TA. High Response Rate and Durability Driven by HLA Genetic Diversity in Patients with Kidney Cancer Treated with Lenvatinib and Pembrolizumab. Mol Cancer Res. 2021 Sep;19(9):1510-1521. doi: 10.1158/1541-7786.MCR-21-0053. Epub 2021 May 26.

    PubMed 34039647

  • Makker V, Taylor MH, Aghajanian C, Oaknin A, Mier J, Cohn AL, Romeo M, Bratos R, Brose MS, DiSimone C, Messing M, Stepan DE, Dutcus CE, Wu J, Schmidt EV, Orlowski R, Sachdev P, Shumaker R, Casado Herraez A. Lenvatinib Plus Pembrolizumab in Patients With Advanced Endometrial Cancer. J Clin Oncol. 2020 Sep 10;38(26):2981-2992. doi: 10.1200/JCO.19.02627. Epub 2020 Mar 13.

    PubMed 32167863

  • Taylor MH, Lee CH, Makker V, Rasco D, Dutcus CE, Wu J, Stepan DE, Shumaker RC, Motzer RJ. Phase IB/II Trial of Lenvatinib Plus Pembrolizumab in Patients With Advanced Renal Cell Carcinoma, Endometrial Cancer, and Other Selected Advanced Solid Tumors. J Clin Oncol. 2020 Apr 10;38(11):1154-1163. doi: 10.1200/JCO.19.01598. Epub 2020 Jan 21.

    PubMed 31961766

  • Makker V, Rasco D, Vogelzang NJ, Brose MS, Cohn AL, Mier J, Di Simone C, Hyman DM, Stepan DE, Dutcus CE, Schmidt EV, Guo M, Sachdev P, Shumaker R, Aghajanian C, Taylor M. Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer: an interim analysis of a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2019 May;20(5):711-718. doi: 10.1016/S1470-2045(19)30020-8. Epub 2019 Mar 25.

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Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Lenvatinib and Pembrolizumab in people with Tumors, run by Eisai Inc. at 64 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 64 sites in United States, Spain, Norway. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1b: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Lenvatinib (time frame: Cycle 1 (21 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02501096, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2023.

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