AzTrials
AzTrials

Solid TumorsPhase 1NCT03006887

Phase 1b Trial of Lenvatinib Plus Pembrolizumab in Participants With Selected Solid Tumors

A Phase 1 study testing lenvatinib and pembrolizumab in people with Solid Tumors, run by Eisai Co., Ltd. at 1 site in Japan.

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 study designed to confirm the tolerability and safety of lenvatinib in combination with pembrolizumab in participants with selected solid tumors (non-small cell lung cancer, predominantly clear cell renal cell carcinoma, endometrial carcinoma, urothelial carcinoma, squamous cell… Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Solid Tumors
What is being tested?
lenvatinib and pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteJapan
Study dates
12 Jan 2017to 15 Apr 2020
Phase
Phase 1
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 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically and/or cytologically confirmed selected solid tumor types that have progressed after treatment with standard therapies or for which there are no other appropriate therapies available.
  • The selected tumor types are: non-small cell lung cancer, predominantly clear cell renal cell carcinoma, endometrial carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, or melanoma (excluding uveal melanoma)
  • At least 1 measurable target lesion according to modified Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
  • Participants must have an Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS) of 0 to 1.
  • Adequate liver function as evidenced by bilirubin ≤1.5×ULN and alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3×ULN (in the case of liver metastases ≤5×ULN). In case ALP is >3×ULN (in the absence of liver metastases) or >5×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 ≥20 years at the time of informed consent
  • Life expectancy of 12 weeks or more
  • Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol

Who cannot join

  • Prior anticancer treatment within 28 days (or 5 times the half-life time, whichever is shorter) or any investigational agent within 28 days prior to the first dose of study drugs. All toxicities related to prior treatments must be resolved to Grade ≤1 (except alopecia).
  • Prior treatment with lenvatinib or any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, excluding cancer types such as melanoma and non-small cell lung cancer where prior treatment with one anti-PD-1, anti-PD-L1, or anti-PD-L2 agent is allowed
  • Participants must have recovered adequately from any complications from major surgery prior to starting therapy.
  • 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 QTc (Fridericia formula) interval to >480 milliseconds (ms)
  • Active infection (any infection requiring systemic treatment)
Show all 14Show fewer
  • Participant is known to be positive for Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C
  • Known intolerance to either of the study drugs (or any of the excipients)
  • History of organ allograft
  • Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis, or has a history of interstitial lung disease
  • Females who are breastfeeding or pregnant at Screening or Baseline.
  • Females of childbearing potential.
  • Participants 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.

Trial locations and contacts

1 site in 1 country.

Japan1 site
  • Eisai Trial Site 1

    Chuo-ku, Tokyo

Other trials in Japan

About this study

Official title: An Open-Label Phase 1b Trial of Lenvatinib Plus Pembrolizumab in Subjects With Selected Solid Tumors

This is an open-label Phase 1b study designed to confirm the tolerability and safety of lenvatinib in combination with pembrolizumab in participants with selected solid tumors (non-small cell lung cancer, predominantly clear cell renal cell carcinoma, endometrial carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, or melanoma [excluding uveal melanoma]).

Conditions
Solid Tumors
Keywords
solid tumors, non-small cell lung cancer, predominantly clear cell renal cell carcinoma, endometrial carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, non-uveal melanoma, E7080, lenvatinib, pembrolizumab, Japan
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Endometrial Neoplasms, Carcinoma, Transitional Cell, Squamous Cell Carcinoma of Head and Neck

What participants receive

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

Study groups in NCT03006887
Study groupRoleWhat they receive
lenvatinib 20 mg plus pembrolizumab 200 mgExperimentalParticipants with selected tumors will receive oral lenvatinib at a starting dose of 20 milligrams (mg) once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks (Q3W) on a 21-day treatment cycle until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.
Receives: Drug: lenvatinib; Drug: pembrolizumab

What is being measured

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

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

    A TEAE was defined as an adverse event (AE) that emerged during the time from the first dose of study drug to 30 days following the last dose of study drug, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. A Serious AE is any untoward medical occurrence that at any dose: resulted in death; was life threatening (that is, the participant was at immediate risk of death from the AE as it occurred; this does not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death) required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or is medically important due to other reasons than the above mentioned criteria.

    Measured: From the first dose until 30 days after the last dose (approximately 2 years 7 months)

  2. Number of Participants With Dose-limiting Toxicities

    A DLT is defined as any of the following: any of the hematological or nonhematological toxicities specified in the protocol that are considered to be at least possibly related to lenvatinib and/or pembrolizumab occurring during Cycle 1; failed to administer greater than or equal to 75 percent (%) of the planned dosage of lenvatinib as a result of treatment-related toxicity during Cycle 1; participants who discontinued due to treatment-related toxicity in Cycle 1; greater than a 2-week delay in starting pembrolizumab in Cycle 2 because of a treatment-related toxicity, even if the toxicity does not meet DLT criteria.

    Measured: Cycle 1 (Cycle length=21 days)

Secondary outcomes (21)
  1. Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1

    ORR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) for target and non-target lesions. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in the short axis to less than 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The tumor assessment was done using number of lesions based on modified RECIST 1.1 for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ.

    Measured: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years 7 months

  2. Duration of Response (DOR) Based on Modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1

    DOR was defined as time from the first documented of CR or PR to the date of first documentation of disease progression (PD) (based on modified RECIST 1.1) or death (whichever occurs first). CR was defined as the disappearance of all target lesions and non-target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD for target lesion, was defined as a minimum 20% increase and a minimum 5 mm absolute increase in sum of diameters compared to nadir, or PD for non-target lesion(s) or unequivocal new lesion(s). Nadir was defined as lowest measure sum of diameters of target lesions at any time point from baseline onward. The tumor assessment was done using number of lesions based on modified RECIST 1.1 for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ. DOR = Date of PD/death (whichever occurs first) - Date of first CR or PR + 1.

    Measured: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years 7 months.

  3. Cmax: Maximum Plasma Concentration of Lenvatinib in Combination With Pembrolizumab

    Measured: Cycle 1 Day 1: 0-24 hours

  4. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Lenvatinib in Combination With Pembrolizumab

    Measured: Cycle 1 Day 1: 0-24 hours

  5. T1/2: Terminal Half-life of Lenvatinib in Combination With Pembrolizumab

    Measured: Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours

  6. AUC(0-t): Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration of Lenvatinib in Combination With Pembrolizumab

    Measured: Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours

  7. AUC(0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Lenvatinib in Combination With Pembrolizumab

    Measured: Cycle 1 Day 1: 0-24 hours

  8. Vz/F: Apparent Volume of Distribution at Terminal Phase of Lenvatinib in Combination With Pembrolizumab

    Measured: Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours

  9. CL/F: Apparent Total Clearance Following Oral Dosing of Lenvatinib in Combination With Pembrolizumab

    Measured: Cycle 1 Day 1: 0-24 hours

  10. MRT: Mean Residence Time of Lenvatinib in Combination With Pembrolizumab

    Measured: Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours

  11. Css,Max: Maximum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab

    Measured: Cycle 1 Day 15: 0-24 hours

  12. Css,Min: Minimum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab

    Measured: Cycle 1 Day 15: 0-24 hours

  13. Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Lenvatinib in Combination With Pembrolizumab

    Measured: Cycle 1 Day 15: 0-24 hours

  14. AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Lenvatinib in Combination With Pembrolizumab

    Measured: Cycle 1 Day 15: 0-24 hours

  15. Clss/F: Apparent Total Clearance Following Oral Administration at Steady State of Lenvatinib in Combination With Pembrolizumab

    Measured: Cycle 1 Day 15: 0-24 hours

  16. Css,Av: Average Steady State Plasma Concentration of Lenvatinib in Combination With Pembrolizumab

    Measured: Cycle 1 Day 15: 0-24 hours

  17. Rac (Cmax): Accumulation Index of Cmax for Lenvatinib in Combination With Pembrolizumab

    Rac (Cmax) was calculated as the ratio of drug concentrations observed during a dosing interval at steady state divided by drug concentrations seen during the dosing interval after a single (first) dose. Rac (Cmax) = Css,max on Cycle 1 Day 15 / Cmax on Cycle 1 Day 1

    Measured: Cycle 1 Day 1: 0-24 hours and Cycle 1 Day 15: 0-24 hours

  18. Rac (AUC): Accumulation Index of AUC for Lenvatinib in Combination With Pembrolizumab

    Rac (AUC) was calculated as the ratio of drug concentrations observed during a dosing interval at steady state divided by drug concentrations seen during the dosing interval after a single (first) dose. Rac (AUC) = AUC(0-t) on Cycle 1 Day 15 / AUC(0-t) on Cycle 1 Day 1.

    Measured: Cycle 1 Day 1: 0-24 hours and Cycle 1 Day 15: 0-24 hours

  19. Lambda z: Terminal Phase Elimination Rate Constant of Lenvatinib in Combination With Pembrolizumab

    Measured: Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours

  20. PTF: Peak-trough Fluctuation Ratio of Lenvatinib in Combination With Pembrolizumab

    The peak trough fluctuation within complete dosing interval at steady state, calculated as PTF (%) = ([Cmax - Cmin]/Cav ) multiplied by 100

    Measured: Cycle 1 Day 15: 0-24 hours

  21. Number of Participants Positive for Serum Anti-drug Antibodies (ADA) Status for Pembrolizumab

    Measured: Day 1 of Cycles 1, 2, 4, 6, and 8 and every 4 cycles thereafter; within 30 days after discontinuation or until the initiation of other anticancer treatment, whichever is earlier (Cycle length=21 days); up to 31 months

Timeline

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

  1. First posted30 Dec 2016 (estimated)
  2. Study start12 Jan 2017
  3. Primary completion15 Apr 2020
  4. Study completion15 Apr 2020

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03006887
Sponsor's protocol ID
E7080-J081-115
Other IDs
KEYNOTE 523
Status last verified
Apr 2021
First submitted
27 Dec 2016
Last updated
20 May 2021
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Kitano S, Fujiwara Y, Shimizu T, Iwasa S, Yonemori K, Kondo S, Shimomura A, Koyama T, Ebata T, Ikezawa H, Hayata N, Minoshima Y, Miura T, Kubota T, Yamamoto N. A feasibility study of lenvatinib plus pembrolizumab in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2022 Dec;90(6):523-529. doi: 10.1007/s00280-022-04480-w. Epub 2022 Oct 26.

    PubMed 36289094

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing lenvatinib and pembrolizumab in people with Solid Tumors, run by Eisai Co., Ltd. at 1 site in Japan.

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 8 inclusion and 14 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 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Japan. 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 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.

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 May 2021). 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?

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (time frame: From the first dose until 30 days after the last dose (approximately 2 years 7 months)). The study lists 2 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 NCT03006887, which also lists 1 linked publication.

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 May 2021.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in