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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03517449




Registration number
NCT03517449
Ethics application status
Date submitted
25/04/2018
Date registered
7/05/2018
Date last updated
18/10/2023

Titles & IDs
Public title
Lenvatinib in Combination With Pembrolizumab Versus Treatment of Physician's Choice in Participants With Advanced Endometrial Cancer (MK-3475-775/E7080-G000-309 Per Merck Standard Convention [KEYNOTE-775])
Scientific title
A Multicenter, Open-label, Randomized, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib in Combination With Pembrolizumab Versus Treatment of Physician's Choice in Participants With Advanced Endometrial Cancer
Secondary ID [1] 0 0
2017-004387-35
Secondary ID [2] 0 0
E7080-G000-309
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endometrial Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

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

Experimental: Lenvatinib 20 mg + Pembrolizumab 200 mg - Participants will receive pembrolizumab 200 milligram (mg) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle plus lenvatinib 20 mg administered orally (PO) once daily (QD) during each 21-day cycle for up to 35 cycles.

Active Comparator: Treatment of Physician's Choice - Participants will receive either of the following treatments: doxorubicin 60 milligram per square meter (mg/m^2) administered by IV on Day 1 of each 21-day cycle for up to a maximum cumulative dose of 500 mg/m^2 OR paclitaxel 80 mg/m^2 administered by IV on a 28-day cycle: 3 weeks receiving paclitaxel once a week and 1 week not receiving paclitaxel.


Treatment: Drugs: Pembrolizumab
200 mg administered by IV infusion on Day 1 of each 21-day cycle.

Treatment: Drugs: Lenvatinib
20 mg administered orally (PO) QD during each 21-day cycle.

Treatment: Drugs: Paclitaxel
80 mg/m^2 administered by IV on a 28-day cycle: 3 weeks receiving paclitaxel once a week and 1 week not receiving paclitaxel.

Treatment: Drugs: Doxorubicin
60 mg/m^2 administered by IV on Day 1 of each 21-day cycle.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS)
Timepoint [1] 0 0
From the date of randomization to the date of the first documentation of disease progression or death, whichever occurred first or up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)
Primary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
From the date of randomization until the date of death from any cause or up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)
Secondary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
From date of randomization up to first documentation of PD or date of death, whichever occurred first up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)
Secondary outcome [2] 0 0
Health-Related Quality of Life (HRQoL) Assessed by European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQC30) Score
Timepoint [2] 0 0
At baseline (prior to first dose of study drug), on Day 1 of each subsequent cycle (cycle length of either 21 or 28 days), and at the post-treatment visit (up to 5 years and 5 months)
Secondary outcome [3] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Immune-Related Adverse Events (irAEs)
Timepoint [3] 0 0
From the first dose of study drug up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)
Secondary outcome [4] 0 0
Percentage of Participants Discontinued Study Treatment Due to TEAEs
Timepoint [4] 0 0
From the first dose of study drug up to data cutoff date 26 October 2020 (up to approximately 2 years 5 months)
Secondary outcome [5] 0 0
Time to Treatment Failure Due to Toxicity
Timepoint [5] 0 0
From the date of randomization to the date of discontinuation of study treatment due to TEAEs (up to 5 years 5 months)
Secondary outcome [6] 0 0
Model Predicted Apparent Total Clearance (CL/F) for Lenvatinib
Timepoint [6] 0 0
Cycle 1 Day 1: 0.5-10 hours post-dose; Cycle 1 Day 15: 0-12 hours post-dose; Cycle 2 Day 1: 0.5-10 hours post-dose (each cycle length=21 days)
Secondary outcome [7] 0 0
Model Predicted Area Under the Plasma Drug Concentration-time Curve (AUC) for Lenvatinib
Timepoint [7] 0 0
Cycle 1 Day 1: 0.5-10 hours post-dose; Cycle 1 Day 15: 0-12 hours post-dose; Cycle 2 Day 1: 0.5-10 hours post-dose (each cycle length=21 days)

Eligibility
Key inclusion criteria
1. Has a histologically confirmed diagnosis of endometrial carcinoma (EC)

2. Documented evidence of advanced, recurrent or metastatic EC.

3. Has radiographic evidence of disease progression after 1 prior systemic,
platinum-based chemotherapy regimen for EC. Participants may have received up to 1
additional line of platinum-based chemotherapy if given in the neoadjuvant or adjuvant
treatment setting.

Note: There is no restriction regarding prior hormonal therapy.

4. Has historical or fresh tumor biopsy specimen for determination of mismatch repair
(MMR) status.

5. Has at least 1 measurable target lesion according to Response Evaluation Criteria In
Solid Tumors (RECIST) 1.1 and confirmed by Blinded Independent Central Review BICR.

6. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7
days of starting study treatment.

7. Is not pregnant, breastfeeding, and agrees to use a highly effective method of
contraception during the treatment period and for at least 120 days (for participants
treated with lenvatinib plus pembrolizumab) or at least 180 days (for participants
treated with treatment of physician's choice [TPC]) after the last dose of study
treatment.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Has carcinosarcoma (malignant mixed mullerian tumor), endometrial leiomyosarcoma and
endometrial stromal sarcomas.

2. Has unstable central nervous system (CNS) metastases.

3. Has active malignancy (except for endometrial cancer, definitively treated in-situ
carcinomas [e.g. breast, cervix, bladder], or basal or squamous cell carcinoma of the
skin) within 24 months of study start.

4. Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other
condition that might affect the absorption of lenvatinib.

5. Has a pre-existing greater than or equal (>=) Grade 3 gastrointestinal or
non-gastrointestinal fistula.

6. Has radiographic evidence of major blood vessel invasion/infiltration.

7. Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the
first dose of study treatment.

8. Has a history of congestive heart failure greater than New York Heart Association
(NYHA) Class II, unstable angina, myocardial infarction, cerebrovascular accident
(CVA) stroke, or cardiac arrhythmia associated with hemodynamic instability within 12
months of the first dose of study treatment.

9. Has an active infection requiring systemic treatment.

10. Has not recovered adequately from any toxicity and/or complications from major surgery
prior to starting therapy.

11. Is positive for Human Immunodeficiency Virus (HIV).

12. Has active Hepatitis B or C.

13. Has a history of (non-infectious) pneumonitis that required treatment with steroids,
or has current pneumonitis.

14. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the study.

15. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to study start -Has an active autoimmune
disease (with the exception of psoriasis) that has required systemic treatment in the
past 2 years.

16. Is pregnant or breastfeeding.

17. Has had an allogenic tissue/solid organ transplant.

18. Has received >1 prior systemic chemotherapy regimen (other than adjuvant or
neoadjuvant) for Endometrial Cancer. Participants may receive up to 2 regimens of
platinum-based chemotherapy in total, as long as one is given in the neoadjuvant or
adjuvant treatment setting.

19. Has received prior anticancer treatment within 28 days of study start. All acute
toxicities related to prior treatments must be resolved to Grade =1, except for
alopecia and Grade =2 peripheral neuropathy.

20. Has received prior treatment with any treatment targeting VEGF-directed angiogenesis,
any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

21. Has received prior treatment with an agent directed to a stimulatory or co-inhibitory
T-cell receptor other than an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, and who has
discontinued from that treatment due to a Grade 3 or higher immune-related adverse
event.

22. Has received prior radiation therapy within 21 days of study start with the exception
of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks of
study start. Participants must have recovered from all radiation-related toxicities
and/or complications prior to randomization.

23. Has received a live vaccine within 30 days of study start.

24. Has a known intolerance to study treatment (or any of the excipients).

25. Prior enrollment on a clinical study evaluating pembrolizumab and lenvatinib for
endometrial carcinoma, regardless of treatment received.

26. Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks of study start.

27. Participants with urine protein =1 gram (g)/24 hour.

28. Prolongation of corrected QT (QTc) interval to >480 milliseconds (ms).

29. Left ventricular ejection fraction (LVEF) below the institutional normal range as
determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).

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



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
11/06/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
7/10/2024
Actual
Sample size
Target
Accrual to date
Final
827
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Royal North Shore Hospital - Sydney
Recruitment hospital [2] 0 0
Royal Brisbane and Women s Hospital - Herston
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 0 0
St John of God - Subiaco
Recruitment postcode(s) [1] 0 0
2065 - Sydney
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
6008 - Subiaco
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
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California
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United States of America
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Connecticut
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Florida
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Georgia
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Illinois
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Louisiana
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Maryland
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New Jersey
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United States of America
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New York
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North Carolina
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Oklahoma
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Oregon
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South Dakota
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Tennessee
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United States of America
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Texas
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Utah
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Argentina
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Buenos Aires
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Argentina
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La Rioja
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Brazil
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GO
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Brazil
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RJ
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Brazil
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RS
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Brazil
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SP
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Brazil
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Belo Horizonte
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Alberta
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Quebec
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Bogota
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Medellin
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Plerin
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Rennes
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Dresden
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Erlangen
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Hamburg
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Rostock
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Tuebingen
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Holon
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Jerusalem
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Israel
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Petah Tikva
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Ramat Gan
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Catania
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Meldola
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Niigata
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Tokyo
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Gyeonggi-do
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Mazowieckie
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Bielsko-Biala
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Gdynia
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Gliwice
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Lodz
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Russian Federation
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Barnaul
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Kazan
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Moscow
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Saint Petersburg
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Saransk
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Tomsk
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Ufa
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Barcelona
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Madrid
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Spain
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Valencia
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Taiwan
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Beitou
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Taiwan
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Kaohsiung
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Taiwan
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Taichung
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Taipei
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Taiwan
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Taoyuan
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Turkey
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Adana
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Ankara
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Bursa
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Istanbul
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Turkey
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Izmir
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United Kingdom
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Brighton
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Cambridge
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London
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United Kingdom
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Southampton

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

Ethics approval
Ethics application status

Summary
Brief summary
This is a study of pembrolizumab (MK-3475, KEYTRUDA®) in combination with lenvatinib (E7080)
versus treatment of physician's choice (doxorubicin or paclitaxel) for the treatment of
advanced endometrial cancer. Participants will be randomly assigned to receive either
pembrolizumab and lenvatinib or treatment of physician's choice. The primary study hypothesis
is that pembrolizumab in combination with lenvatinib prolongs progression free survival (PFS)
and overall survival (OS) when compared to treatment of physician's choice.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03517449
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Eisai Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03517449