CompletedNCT02501096Updated Jul 20, 2023Results posted

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

A Phase 1/2 interventional study of Lenvatinib and Pembrolizumab in Tumors, sponsored by Eisai Inc.. Completed at 64 sites in 3 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-07-20.

Sponsored by Eisai Inc. · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 357
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study 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 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 studied

Tumors

Browse trials for

Neoplasms 9,365

Keywords

Lenvatinib
Lenvima
E7080
Phase 1b/2
Pembrolizumab
Keytruda
Solid tumors

In context

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,486 are open to participants now.

This study's enrollment of 357 is above the median of 50 across 7,250 interventional studies indexed under Neoplasms.

Browse Neoplasms studies →

Lead sponsor

Eisai Inc. is the lead sponsor of 360 studies on the registry; 7 are open to participants now.

Of its 81 completed or terminated interventional studies of FDA-regulated products, 54 (67%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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:
1. 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)
2. 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
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:
1. Absolute neutrophil count (ANC) greater than or equal to 1500/mm3 (greater than or equal to 1.5 X 103/uL)
2. Platelets greater than or equal to 100,000/mm3 (greater than or equal to 100 X 109/L)
3. 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.

Exclusion criteria

Exclusion Criteria:

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
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.

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 357 participants (actual)

Study arms

Experimental
Lenvatinib + Pembrolizumab
Participants 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.
Drug: Lenvatinib · Drug: Pembrolizumab

Interventions

DrugLenvatinib
Lenvatinib will be administered with water orally once a day (with or without food) continuously in 21-day treatment cycle.
Also known as: Lenvima, E7080
DrugPembrolizumab
Pembrolizumab will be administered as a dose of 200 mg Q3W, IV in 21-day treatment cycle.
Also known as: Keytruda, MK-3475

What researchers measure

Primary outcomes

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).
Time frame: Cycle 1 (21 days)
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.
Time frame: Cycle 1 (21 days)
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.
Time frame: Week 24

Secondary outcomes

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.
Time frame: From date of first dose up to 30 days after the last dose of study drugs (Up to 74 months)
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.
Time frame: 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)
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).
Time frame: From date of first dose of study drug administration to date of irPD or date of death, whichever occurred first (up to 73 months)
Overall Survival (OS)
OS was defined as the time from the first dose date to the date of death from any cause.
Time frame: From the first dose until death from any cause, up to 73 months
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).
Time frame: 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)
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).
Time frame: 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)
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.
Time frame: 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)
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.
Time frame: First documentation of irCR or irPR until first documentation of progression or death (up to 73 months)
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.
Time frame: 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)
Plasma Concentrations of Lenvatinib
Observed plasma concentration of Lenvatinib was reported here quantified by LCMS/MS method.
Time frame: 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):

Results

Posted Jul 20, 2023

Participant flow

Participants took part in the study at 62 investigative sites in the United States, Spain and Norway from 22 July 2015 to 11 July 2022.

Participant flow — Overall Study
Milestone	Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: RCC	Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: NSCLC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: EC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: RCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: Melanoma	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: NSCLC	Phase 1b and 2,Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: HNSCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: UC	Phase1b and 2, Lenvatinib 20mg/Day+Pembrolizumab 200 mg: Leiomyosarcoma
Started	2	1	124	145	21	21	22	20	1
Phase 1b participants who received, lenvatinib 20 mg/day + pembrolizumab 200 mg.	0	0	2	6	1	1	0	0	0
Phase 2 participants who received, lenvatinib 20 mg/day + pembrolizumab 200 mg	0	0	122	139	20	20	22	20	1
Completed	0	0	0	0	0	0	0	0	0
Not completed	2	1	124	145	21	21	22	20	1
Withdrew: Lost to follow-up	0	0	0	0	1	1	3	0	0
Withdrew: Withdrawal by subject	1	0	7	13	2	2	2	3	0
Withdrew: Survival follow-up discontinued by sponsor	0	0	29	58	3	2	2	1	0
Withdrew: Death	1	1	88	74	15	16	15	16	1

Outcome measures

PrimaryPhase 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).

Time frame:: Cycle 1 (21 days)
Reported as:: Number · milligram (mg)

Phase 1b: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Lenvatinib
milligram (mg)	Phase 1b: All Participants
MTD	20
RP2D	20

PrimaryPhase 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.

Time frame:: Cycle 1 (21 days)
Reported as:: Count of participants · Participants

Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs) of Lenvatinib
Participants	Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: RCC	Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: NSCLC	Phase 1b, Lenvatinib 20 mg/Day + Pembrolizumab 200 mg: NSCLC	Phase 1b, Lenvatinib 20 mg/Day + Pembrolizumab 200 mg: RCC	Phase 1b, Lenvatinib 20 mg/Day + Pembrolizumab 200 mg: EC	Phase 1b, Lenvatinib 20 mg/Day + Pembrolizumab 200 mg: Melanoma
Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs) of Lenvatinib	1	1	0	0	0	0

PrimaryObjective 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.

Time frame:: Week 24
Reported as:: Number · percentage of participants

Objective Response Rate (ORR) Based on Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) Version 1.1 at Week 24
percentage of participants	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: EC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: RCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: Melanoma	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: NSCLC	Phase 1b and 2,Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: HNSCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: UC	Phase1b and 2, Lenvatinib 20mg/Day+Pembrolizumab 200 mg: Leiomyosarcoma
Objective Response Rate (ORR) Based on Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) Version 1.1 at Week 24	39.5 (30.9 to 48.7)	56.6 (48.1 to 64.8)	47.6 (25.7 to 70.2)	23.8 (8.2 to 47.2)	31.8 (13.9 to 54.9)	25.0 (8.7 to 49.1)	0 (NA to NA)

SecondaryNumber 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.

Time frame:: From date of first dose up to 30 days after the last dose of study drugs (Up to 74 months)
Reported as:: Count of participants · Participants

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Participants	Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: RCC	Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: NSCLC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: EC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: RCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: Melanoma	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: NSCLC	Phase 1b and 2,Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: HNSCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: UC	Phase1b and 2, Lenvatinib 20mg/Day+Pembrolizumab 200 mg: Leiomyosarcoma
TEAEs	2	1	124	145	21	21	22	20	1
TESAEs	1	1	73	81	12	15	12	17	0

SecondaryObjective 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.

Time frame:: 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)
Reported as:: Number · percentage of participants

Objective Response Rate (ORR) Based on irRECIST Version 1.1
percentage of participants	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: EC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: RCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: Melanoma	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: NSCLC	Phase 1b and 2,Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: HNSCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: UC	Phase1b and 2, Lenvatinib 20mg/Day+Pembrolizumab 200 mg: Leiomyosarcoma
Objective Response Rate (ORR) Based on irRECIST Version 1.1	40.3 (31.6 to 49.5)	63.4 (55.1 to 71.3)	47.6 (25.7 to 70.2)	23.8 (8.2 to 47.2)	40.9 (20.7 to 63.6)	25.0 (8.7 to 49.1)	NA (NA to NA)

SecondaryProgression-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).

Time frame:: From date of first dose of study drug administration to date of irPD or date of death, whichever occurred first (up to 73 months)
Reported as:: Median · months

Progression-free Survival (PFS) Based on irRECIST Version 1.1
months	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: EC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: RCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: Melanoma	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: NSCLC	Phase 1b and 2,Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: HNSCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: UC	Phase1b and 2, Lenvatinib 20mg/Day+Pembrolizumab 200 mg: Leiomyosarcoma
Progression-free Survival (PFS) Based on irRECIST Version 1.1	7.5 (5.3 to 9.7)	14.1 (11.6 to 18.4)	5.5 (2.6 to 15.8)	5.4 (2.3 to 7.4)	4.4 (4.0 to 9.8)	5.4 (1.3 to 42.3)	1.35 (NA to NA)

SecondaryOverall Survival (OS)

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

Time frame:: From the first dose until death from any cause, up to 73 months
Reported as:: Median · months

Overall Survival (OS)
months	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: EC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: RCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: Melanoma	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: NSCLC	Phase 1b and 2,Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: HNSCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: UC	Phase1b and 2, Lenvatinib 20mg/Day+Pembrolizumab 200 mg: Leiomyosarcoma
Overall Survival (OS)	19.9 (16.2 to 25.9)	32.2 (29.8 to 55.8)	25.4 (8.6 to 39.5)	11.4 (3.6 to 23.3)	16.2 (8.6 to 31.8)	6.1 (2.4 to 30.1)	16.56 (NA to NA)

SecondaryDisease 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).

Time frame:: 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)
Reported as:: Number · percentage of participants

Disease Control Rate (DCR) Based on irRECIST Version 1.1
percentage of participants	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: EC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: RCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: Melanoma	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: NSCLC	Phase 1b and 2,Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: HNSCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: UC	Phase1b and 2, Lenvatinib 20mg/Day+Pembrolizumab 200 mg: Leiomyosarcoma
Disease Control Rate (DCR) Based on irRECIST Version 1.1	84.7 (77.1 to 90.5)	93.8 (88.5 to 97.1)	81.0 (58.1 to 94.6)	76.2 (52.8 to 91.8)	90.9 (70.8 to 98.9)	70.0 (45.7 to 88.1)	NA (NA to NA)

SecondaryClinical 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).

Time frame:: 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)
Reported as:: Number · percentage of participants

Clinical Benefit Rate (CBR) Based on irRECIST Version 1.1
percentage of participants	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: EC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: RCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: Melanoma	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: NSCLC	Phase 1b and 2,Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: HNSCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: UC	Phase1b and 2, Lenvatinib 20mg/Day+Pembrolizumab 200 mg: Leiomyosarcoma
Clinical Benefit Rate (CBR) Based on irRECIST Version 1.1	58.9 (49.7 to 67.6)	80.0 (72.6 to 86.2)	61.9 (38.4 to 81.9)	57.1 (34.0 to 78.2)	45.5 (24.4 to 67.8)	40.0 (19.1 to 63.9)	NA (NA to NA)

SecondaryDurable 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.

Time frame:: 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)

No measurements were reported for this outcome.

SecondaryDuration 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.

Time frame:: First documentation of irCR or irPR until first documentation of progression or death (up to 73 months)
Reported as:: Median · months

Duration of Objective Response (DOR) Based on irRECIST Version 1.1
months	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: EC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: RCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: Melanoma	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: NSCLC	Phase 1b and 2,Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: HNSCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: UC	Phase1b and 2, Lenvatinib 20mg/Day+Pembrolizumab 200 mg: Leiomyosarcoma
Duration of Objective Response (DOR) Based on irRECIST Version 1.1	NA (8.5 to NA)	16.6 (9.7 to 18.4)	12.5 (2.7 to 28.6)	14.5 (2.4 to NA)	7.1 (2.2 to 16.8)	41.0 (4.6 to NA)	—

SecondaryPhase 1b: Plasma Concentrations of Lenvatinib

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

Time frame:: 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)
Reported as:: Mean · microgram per liter (mcg/L)

Phase 1b: Plasma Concentrations of Lenvatinib
microgram per liter (mcg/L)	Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: RCC	Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: NSCLC
Cycle 1 Day 1: 0.5-4 hour	102.5 ± 136.44	198.0 ± NA
Cycle 1 Day 1: 6-10 hour	210.5 ± 65.76	—
Cycle 1 Day 15: Predose	53.9 ± NA	1.8 ± NA
Cycle 1 Day 15: 0.5-4 hour	78.4 ± NA	2.6 ± NA
Cycle 1 Day 15: 6-10 hour	366.0 ± NA	424.0 ± NA
Cycle 2 Day 1: Predose	35.4 ± 13.08	364.0 ± NA
Cycle 2 Day 1: 2-12 hour	491.0 ± 247.49	374.0 ± NA
Cycle 3 Day 1: Predose	23.3 ± 31.92	118.0 ± NA
Cycle 4 Day 1: Predose	28.0 ± 13.93	176.0 ± NA
Cycle 5 Day 1: Predose	19.9 ± 14.91	2.5 ± NA
Cycle 6 Day 1: Predose	44.4 ± 42.64	210.0 ± NA

SecondaryPlasma Concentrations of Lenvatinib

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

Time frame:: 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):
Reported as:: Mean · mcg/L

Plasma Concentrations of Lenvatinib
mcg/L	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: EC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: RCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: Melanoma	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: NSCLC	Phase 1b and 2,Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: HNSCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: UC	Phase1b and 2, Lenvatinib 20mg/Day+Pembrolizumab 200 mg: Leiomyosarcoma
Cycle 1 Day 1:0.5-4 hour	82.2 ± 145.44	35.5 ± 78.13	24.0 ± 33.59	79.9 ± 118.94	41.8 ± 100.34	123.8 ± 169.05	—
Cycle 1 Day 1:6-10 hour	231.7 ± 109.67	190.8 ± 96.25	154.3 ± 69.56	224.1 ± 109.95	169.7 ± 95.78	214.2 ± 86.51	116 ± NA
Cycle 1 Day 15:Predose	66.6 ± 36.56	67.2 ± 80.70	52.1 ± 61.70	62.9 ± 87.36	60.9 ± 46.38	61.1 ± 69.54	52.2 ± NA
Cycle 1 Day 15:0.5-4 hour	129.3 ± 109.72	122.4 ± 114.62	93.1 ± 117.35	275.3 ± 305.30	142.8 ± 149.90	153.9 ± 135.79	45.9 ± NA
Cycle 1 Day 15:6-10 hour	271.3 ± 103.60	206.3 ± 97.29	241.8 ± 241.52	266.8 ± 146.41	210.6 ± 78.37	249.7 ± 91.65	161 ± NA
Cycle 2 Day 1:Predose	57.2 ± 60.58	54.6 ± 64.43	49.2 ± 46.63	51.6 ± 66.72	42.0 ± 48.16	22.3 ± 21.61	26.1 ± NA
Cycle 2 Day 1:2-12 hour	199.7 ± 155.08	171.7 ± 119.34	218.6 ± 83.83	295.0 ± 190.80	166.5 ± 128.95	204.7 ± 174.60	—
Cycle 3 Day 1:Predose	53.2 ± 59.53	59.0 ± 67.58	62.8 ± 65.77	99.4 ± 132.33	43.7 ± 50.45	37.9 ± 29.19	—
Cycle 4 Day 1:Predose	50.7 ± 52.16	56.0 ± 61.56	65.8 ± 115.31	53.4 ± 81.66	34.3 ± 54.94	18.8 ± 34.33	61.9 ± NA
Cycle 5 Day 1:Predose	53.5 ± 56.69	52.1 ± 65.15	60.8 ± 58.38	71.8 ± 134.39	37.7 ± 42.97	39.0 ± 29.50	—
Cycle 6 Day 1:Predose	40.6 ± 33.66	51.8 ± 49.19	114.0 ± 189.97	49.9 ± 68.97	36.9 ± 34.12	34.2 ± 31.86	—

Adverse events

Collected over From date of first dose of the study drugs up to 30 days after the last dose (up to 74 months). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: RCC	1/2 (50%)	1/2 (50%)	2/2 (100%)
Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: NSCLC	1/1 (100%)	1/1 (100%)	1/1 (100%)
Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: EC	88/124 (71%)	73/124 (58.9%)	122/124 (98.4%)
Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: RCC	74/145 (51%)	81/145 (55.9%)	145/145 (100%)
Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: Melanoma	15/21 (71.4%)	12/21 (57.1%)	21/21 (100%)
Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: NSCLC	16/21 (76.2%)	15/21 (71.4%)	21/21 (100%)
Phase 1b and 2,Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: HNSCC	15/22 (68.2%)	12/22 (54.5%)	22/22 (100%)
Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: UC	16/20 (80%)	17/20 (85%)	20/20 (100%)
Phase1b and 2, Lenvatinib 20mg/Day+Pembrolizumab 200 mg: Leiomyosarcoma	1/1 (100%)	0/1 (0%)	1/1 (100%)

Most frequent serious events

Showing 10 of 207

Most frequent serious events
Event	Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: RCC	Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: NSCLC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: EC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: RCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: Melanoma	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: NSCLC	Phase 1b and 2,Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: HNSCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: UC	Phase1b and 2, Lenvatinib 20mg/Day+Pembrolizumab 200 mg: Leiomyosarcoma
EncephalopathyNervous system disorders	0/2	1/1	3/124	1/145	0/21	0/21	0/22	0/20	0/1
Clostridial sepsisInfections and infestations	1/2	0/1	0/124	0/145	0/21	0/21	0/22	0/20	0/1
SepsisInfections and infestations	0/2	0/1	1/124	3/145	0/21	0/21	0/22	3/20	0/1
AstheniaGeneral disorders	0/2	0/1	2/124	1/145	1/21	0/21	0/22	2/20	0/1
PneumoniaInfections and infestations	0/2	0/1	1/124	6/145	0/21	1/21	1/22	2/20	0/1
Acute kidney injuryRenal and urinary disorders	0/2	0/1	1/124	6/145	0/21	0/21	1/22	2/20	0/1
DiarrhoeaGastrointestinal disorders	0/2	0/1	2/124	3/145	0/21	2/21	0/22	0/20	0/1
CholecystitisHepatobiliary disorders	0/2	0/1	0/124	3/145	2/21	0/21	0/22	0/20	0/1
SeizureNervous system disorders	0/2	0/1	1/124	0/145	2/21	0/21	0/22	0/20	0/1
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders	0/2	0/1	0/124	0/145	0/21	2/21	1/22	0/20	0/1

Most frequent other events

Showing 10 of 162

Most frequent other events
Event	Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: RCC	Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: NSCLC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: EC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: RCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: Melanoma	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: NSCLC	Phase 1b and 2,Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: HNSCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: UC	Phase1b and 2, Lenvatinib 20mg/Day+Pembrolizumab 200 mg: Leiomyosarcoma
HypothyroidismEndocrine disorders	1/2	1/1	61/124	60/145	7/21	8/21	6/22	8/20	0/1
DiarrhoeaGastrointestinal disorders	2/2	1/1	79/124	97/145	13/21	12/21	8/22	11/20	0/1
DyspepsiaGastrointestinal disorders	0/2	1/1	12/124	21/145	3/21	1/21	0/22	2/20	0/1
NauseaGastrointestinal disorders	2/2	0/1	66/124	74/145	13/21	10/21	9/22	12/20	0/1
StomatitisGastrointestinal disorders	2/2	1/1	45/124	63/145	1/21	5/21	7/22	2/20	1/1
VomitingGastrointestinal disorders	1/2	0/1	56/124	44/145	9/21	8/21	6/22	10/20	1/1
FatigueGeneral disorders	2/2	1/1	66/124	95/145	14/21	15/21	11/22	12/20	1/1
Skin infectionInfections and infestations	2/2	0/1	0/124	0/145	0/21	0/21	0/22	0/20	0/1
Urinary tract infectionInfections and infestations	0/2	1/1	37/124	8/145	6/21	3/21	2/22	9/20	0/1
Decreased appetiteMetabolism and nutrition disorders	2/2	1/1	68/124	70/145	10/21	16/21	10/22	10/20	0/1

Baseline characteristics

The safety analysis set included all participants who received at least one dose of study drug.

Age, Customized
Age, Customized(Participants)	Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: RCC	Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: NSCLC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: EC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: RCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: Melanoma	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: NSCLC	Phase 1b and 2,Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: HNSCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: UC	Phase1b and 2, Lenvatinib 20mg/Day+Pembrolizumab 200 mg: Leiomyosarcoma	Total
<65 years	0	0	47	88	16	9	9	4	1	174
>=65 years	2	1	77	57	5	12	13	16	0	183

Sex: Female, Male
Sex: Female, Male(Participants)	Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: RCC	Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: NSCLC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: EC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: RCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: Melanoma	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: NSCLC	Phase 1b and 2,Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: HNSCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: UC	Phase1b and 2, Lenvatinib 20mg/Day+Pembrolizumab 200 mg: Leiomyosarcoma	Total
Female	0	1	124	32	4	10	4	6	1	182
Male	2	0	0	113	17	11	18	14	0	175

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: RCC	Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: NSCLC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: EC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: RCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: Melanoma	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: NSCLC	Phase 1b and 2,Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: HNSCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: UC	Phase1b and 2, Lenvatinib 20mg/Day+Pembrolizumab 200 mg: Leiomyosarcoma	Total
Hispanic or Latino	1	0	3	17	2	0	1	2	0	26
Not Hispanic or Latino	1	1	121	128	19	21	21	18	1	331
Unknown or Not Reported	0	0	0	0	0	0	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: RCC	Phase 1b, Lenvatinib 24 mg/Day + Pembrolizumab 200 mg: NSCLC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: EC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: RCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: Melanoma	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: NSCLC	Phase 1b and 2,Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: HNSCC	Phase 1b and 2, Lenvatinib 20 mg/Day+Pembrolizumab 200 mg: UC	Phase1b and 2, Lenvatinib 20mg/Day+Pembrolizumab 200 mg: Leiomyosarcoma	Total
American Indian or Alaska Native	0	0	1	0	0	0	0	0	0	1
Asian	0	0	5	3	0	0	0	0	0	8
Native Hawaiian or Other Pacific Islander	0	0	1	0	0	0	0	0	0	1
Black or African American	0	0	7	6	0	3	2	0	1	19
White	2	1	108	125	19	18	20	19	0	312
More than one race	0	0	2	8	1	0	0	1	0	12
Unknown or Not Reported	0	0	0	3	1	0	0	0	0	4

Study locations

64 sites

Alaska Clinical Research Center
Anchorage, Alaska, United States
Arizona Oncology Associates
Oro Valley, Arizona, United States
Arizona Oncology Associates, PC - HOPE, Site #1
Tucson, Arizona, United States
Arizona Oncology Associates, PC - HOPE, Site #2
Tucson, Arizona, United States
Arizona Oncology Associates, PC - HOPE, Site #3
Tucson, Arizona, United States
Rocky Mountain Cancer Centers
Aurora, Colorado, United States
Rocky Mountain Cancer Centers
Boulder, Colorado, United States
Rocky Mountain Cancer Centers
Colorado Springs, Colorado, United States
Rocky Mountain Cancer Centers, Site #1
Denver, Colorado, United States
Rocky Mountain Cancer Centers, Site #2
Denver, Colorado, United States
Rocky Mountain Cancer Centers
Lakewood, Colorado, United States
Rocky Mountain Cancer Centers
Littleton, Colorado, United States
Rocky Mountain Cancer Centers
Lone Tree, Colorado, United States
Rocky Mountain Cancer Centers
Longmont, Colorado, United States
Rocky Mountain Cancer Centers
Parker, Colorado, United States
Rocky Mountain Cancer Centers
Pueblo, Colorado, United States
Rocky Mountain Cancer Centers
Thornton, Colorado, United States
Baptist Health Medical Group Oncology, LLC, Site #1
Miami, Florida, United States
Baptist Health Medical Group Oncology, LLC, Site #2
Miami, Florida, United States
Baptist Health Medical Group Oncology, LLC, Site #3
Miami, Florida, United States
Boca Raton Clinical Research Medical Center
Plantation, Florida, United States
Piedmont Cancer Institue
Atlanta, Georgia, United States
The University of Chicago
Chicago, Illinois, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Mass General Hospital
Boston, Massachusetts, United States
University of Minnesota, Masonic Cancer Center
Minneapolis, Minnesota, United States
Comprehensive Cancer Centers of Nevada, Site #1
Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada, Site #2
Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada, Site #3
Henderson, Nevada, United States
Comprehensive Cancer Centers of Nevada, Site #1
Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada, Site #2
Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada, Site #3
Las Vegas, Nevada, United States
Comprehensive Cancer Centers of Nevada, Site #4
Las Vegas, Nevada, United States
New York Hematology Oncology (US Onc)
Albany, New York, United States
Memorial Sloan Kettering at Westchester
Harrison, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Oregon Health & Science University
Portland, Oregon, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Texas Oncology-Bedford
Bedford, Texas, United States
Texas Oncology (US Onc)
Dallas, Texas, United States
Texas Oncology
Dallas, Texas, United States
Texas Oncology-Denton South
Denton, Texas, United States
Texas Oncology-Fort Worth, Site #1
Fort Worth, Texas, United States
Texas Oncology-Grapevine
Grapevine, Texas, United States
Texas Oncology-Longview Cancer Center
Longview, Texas, United States
Texas Oncology-Plano West
Plano, Texas, United States
South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, United States
Texas Oncology-Tyler
Tyler, Texas, United States
Texas Oncology-Waco, Site #1
Waco, Texas, United States
Texas Oncology-Waco, Site #2
Waco, Texas, United States
Haukeland Univerity Hospital
Bergen, Norway
Sørlandet Hospital
Kristiansand, 4604, Norway
Akershus Universitetssykehus HF
Lørenskog, Norway
Oslo Univerity Hospital
Oslo, Norway
Sykehuset Østfold
Sarpsborg, Norway
Hospital Universitari Germans Trias i Pujol
Badalona, Spain
Hospital Universitari Vall d'Hebron
Barcelona, Spain
Hospital Universitario De Fuenlabrada
Fuenlabrada, Spain
Hospital La Paz
Madrid, Spain
Hospital Universitario Clinico San Carlos
Madrid, Spain
MD Anderson Cancer Center Madrid - España
Madrid, Spain
Parc Taulí Sabadell
Sabadell, Spain
Hospital Virgen de la Salud
Toledo, Spain
Hospital Universitari i Politécnic La Fe.
Valencia, Spain

References and documents

Publications

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. Erratum In: J Clin Oncol. 2020 Aug 10;38(23):2702. doi: 10.1200/JCO.20.01942. 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. PubMed 30922731 ↗

Study documents

Study protocol · Jul 30, 2021
Statistical analysis plan · Sep 16, 2020

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jul 20, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02501096
Lead sponsor: Eisai Inc.
Collaborators: Merck Sharp & Dohme LLC
Responsible party: Sponsor
First posted: Jul 17, 2015
Start date: Jul 22, 2015
Primary completion: Aug 18, 2020
Completion: Jul 11, 2022
Results posted: Jul 20, 2023
Last update: Jul 20, 2023

Oversight

FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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