Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Versus Chemotherapy for Endometrial Carcinoma (ENGOT-en9 / MK-7902-001) - China Extension Study

Endometrial Neoplasms Clinical Trial

— LEAP-001  

Official title:

A Phase 3 Randomized, Open-Label, Study of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Versus Chemotherapy for First-line Treatment of Advanced or Recurrent Endometrial Carcinoma (LEAP-001)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04865289
• Other study ID #: 7902-001 China Extension
• Secondary ID: MK-7902-001ENGOT
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 22, 2019
• Est. completion date: January 15, 2025

Study information

• Verified date: June 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the efficacy of pembrolizumab + lenvatinib to chemotherapy in female participants with Stage III, IV, or recurrent endometrial carcinoma. It is hypothesized that the combination of pembrolizumab + lenvatinib will be superior to chemotherapy for progression-free survival (PFS) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR). It is also hypothesized that the combination of pembrolizumab + lenvatinib will be superior to chemotherapy for overall survival (OS).

As of Amendment 7 eligible participants on study completion will be able to transition to an extension study, if available, in which they can continue to receive pembrolizumab monotherapy, lenvatinib monotherapy, or a combination of both pembrolizumab and lenvatinib as received in the parent study.

Description:

This China extension study will include participants previously enrolled in China in the global study for MK-7902-001 (NCT03884101) plus those enrolled during the China extension enrollment period.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 130
• Est. completion date: January 15, 2025
• Est. primary completion date: October 2, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has Stage III, Stage IV, or recurrent, histologically-confirmed endometrial carcinoma with disease that is either measurable or nonmeasurable but radiographically apparent, per RECIST 1.1 as assessed by BICR (note: may have received prior chemotherapy only if administered concurrently with radiation; may have received prior radiation without concurrent chemotherapy; may have received prior hormonal therapy for treatment of endometrial carcinoma, provided that it was discontinued =1 week prior to randomization; and may have received 1 prior line of systemic platinum-based adjuvant and/or neoadjuvant chemotherapy)

• Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion that was not previously irradiated, for determination of mismatch repair (MMR) status

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 7 days prior to the first dose of study intervention

• Is not pregnant or breastfeeding, and is either not a woman of childbearing potential (WOCBP) or is a WOCBP who agrees to use contraception during the study and for =120 days after pembrolizumab, =30 days after lenvatinib, or =180 days after (chemotherapy) [if a WOCBP, a pregnancy test will be required within 24 hours of first dose of study drug]

• Has adequately controlled blood pressure within 7 days prior to randomization

• Has adequate organ function based on assessment within 7 days prior to the first dose of study intervention

Exclusion Criteria:

• Has carcinosarcoma (malignant mixed Mullerian tumor), endometrial leiomyosarcoma or other high grade sarcomas, or endometrial stromal sarcomas

• Has a central nervous system (CNS) metastasis, unless local therapy (e.g., whole brain radiation therapy, surgery, or radiosurgery) has been completed and have discontinued use of corticosteroids for this indication for =4 weeks prior to starting study medication (major surgery within 3 weeks of the first dose of study drug will be exclusionary)

• Has a known additional malignancy (other than endometrial carcinoma) that is progressing or has required active treatment in the last 3 years

• Has gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib

• Has a pre-existing Grade =3 gastrointestinal or nongastrointestinal fistula

• Has radiographic evidence of major blood vessel invasion/infiltration

• Has active hemoptysis (bright red blood of =0.5 teaspoon) within 3 weeks prior to the first dose of study intervention, or tumor bleeding within 2 weeks prior to randomization

• Has clinically significant cardiovascular disease within 12 months from first dose of study intervention including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability

• Has any infection requiring systemic treatment

• Has not recovered adequately from any toxicity and/or complications from major surgery prior to randomization

• Has a known history of human immunodeficiency virus (HIV) infection (HIV test is required at screening)

• Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (hepatitis B and C testing is required at screening)

• Has a history of (noninfectious) pneumonitis that required treatment with steroids, or has current pneumonitis

• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator

• Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study

• 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 randomization

• Has an active autoimmune disease (with the exception of psoriasis) that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs)

• Has received prior systemic chemotherapy in any setting for the treatment of endometrial carcinoma (note: prior chemotherapy administered concurrently with radiation is permitted)

• Has received prior radiotherapy within 4 weeks prior to randomization (participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis - a 2-week washout is permitted for palliative radiation to non-CNS disease and vaginal brachytherapy)

• Has received prior hormonal therapy for the treatment of endometrial carcinoma within 1 week of randomization

• Has received prior therapy with any treatment targeting vascular endothelial growth factor (VEGF)-directed angiogenesis, an anti-programmed cell death (PD)-1, anti-PD ligand (L)1, or anti-PD L2 agent, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137)

• Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention

• Has known intolerance to study intervention (or any of the excipients)

• Has had an allogenic tissue/solid organ transplant

• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to randomization

Related Conditions & MeSH terms

• Endometrial Neoplasms

Intervention

Drug:
• Lenvatinib
Lenvatinib 4 mg or 10 mg capsules at a total daily dose of 20 mg taken by mouth once per day.

Biological:
• Pembrolizumab
Pembrolizumab 200 mg IV infusion given on Day 1 of each cycle.

Drug:
• Paclitaxel
Paclitaxel 175 mg/m^2 IV infusion given on Day 1 of each cycle.
• Carboplatin
Carboplatin 10 mg/mL IV infusion at a total dose of are-under-the-curve (AUC) 6 (per Calvert's formula) given on Day 1 of each cycle.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital ( Site 2504)	Beijing	Beijing
China	Beijing Obstetrics and Gynecology Hospital Capital Medical University ( Site 2505)	Beijing	Beijing
China	Peking Union Medical College Hospital ( Site 2501)	Beijing	Beijing
China	The First Hospital Of Jilin University ( Site 2518)	Changchun	Jilin
China	Hunan Cancer Hospital ( Site 2523)	Changsha	Hunan
China	Xiangya Hospital Central-South University ( Site 2512)	Changsha	Hunan
China	Chongqing Cancer Hospital ( Site 2513)	Chongqing	Chongqing
China	The First Affiliated Hospital.Sun Yat-sen University ( Site 2507)	Guangzhou	Guangdong
China	Women s Hospital School of Medicine Zhejiang University ( Site 2511)	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital ( Site 2506)	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital ( Site 2520)	Harbin	Heilongjiang
China	Anhui Cancer Hospital-Gynecological Oncology ( Site 2509)	Hefei	Anhui
China	Jiangxi Maternal and Child Health Hospital ( Site 2519)	Nanchang	Jiangxi
China	Nanjing Maternity and Child Health Care Hospital ( Site 2508)	Nanjing	Jiangsu
China	Guang Xi Tumour Hospital, Department of Chemotherapy ( Site 2517)	Nanning	Guangxi
China	Fudan University Shanghai Cancer Center ( Site 2500)	Shanghai	Shanghai
China	Obstetrics and Gynecology Hosp. Fudan University ( Site 2503)	Shanghai	Shanghai
China	Shanghai First Maternity and Infant Hospital ( Site 2524)	Shanghai	Shanghai
China	The First Affiliated Hospital of Xinjiang Medical University ( Site 2515)	Urumqi	Xinjiang
China	Hubei Cancer Hospital ( Site 2510)	Wuhan	Hubei
China	The first affiliated Hospital of Xi an Jiaotong University ( Site 2502)	XI An	Shaanxi
China	The First Affiliated hospital of Xiamen University-Obstetrics and gynecology department ( Site 2522)	Xiamen	Fujian

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	Eisai Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR)	Progression-free survival based on RECIST 1.1 as assessed by BICR. Progression-free survival is measured from the time of randomization to the first documented disease progression or death due to any cause, whichever occurs first.	Up to approximately 31 months
Primary	Overall Survival (OS)	Overall survival is measured from the time of randomization up to death due to any cause.	Up to approximately 45 months
Secondary	Objective response rate (ORR ) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent review (BICR)	The ORR (either confirmed complete response [CR] or partial response [PR]) based on RECIST 1.1 and assessed by BICR will be determined in mismatch repair proficient (pMMR) participants and in all-comer participants who have measurable disease at study entry.	Up to approximately 31 months
Secondary	Change from baseline in the global score of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) in pMMR and in all-comer participants	The EORTC QLQ-C30 was developed to assess the quality of life of patients with cancer. It contains 30 questions (items), 24 of which aggregate into nine multi-item scales representing various aspects, or dimensions, of quality of life (QoL): one global scale, five functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea, pain), and six additional single-symptom items assessing additional symptoms commonly reported by cancer patients (dyspnoea, loss of appetite, insomnia, constipation and diarrhoea) and perceived financial impact of the disease. Individual items are scored on a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Raw scores for each scale are standardized into a range of 0 to 100 by linear transformation; a higher score on the global and functional scales represents a higher ("better") level of functioning, and a higher score on the symptom scale represents a higher ("worse") level of symptoms.	Baseline and designated time points up to 27 months
Secondary	Percentage of participants experiencing an adverse event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.	Up to approximately 27 months (through 90 days after the last dose of study treatment)
Secondary	Percentage of participants experiencing a serious adverse event (SAE)	An SAE is an AE that results in death, is life-threatening, requires or prolongs hospitalization, results in persistent or significant disability, is a congenital birth defect, or is another important medical event.	Up to approximately 28 months (through 120 days after the last dose of study treatment)
Secondary	Percentage of participants experiencing an immune-related AE (irAE)	Immune-related AEs will be monitored in both arms.	Up to approximately 27 months (through 90 days after the last dose of study treatment)
Secondary	Percentage of participants discontinuing from study treatment due to an AE(s)	Discontinuations related to AEs will be monitored in both arms.	Up to approximately 24 months (through the last dose of study treatment)

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary