Clinical trial NCT04865289: Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Versus Chemotherapy for Endometrial Carcinoma (ENGOT-en9 / MK-7902-001) - China Extension Study
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Endometrial Neoplasms
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Eisai Inc.
First posted: 2021-04-29
Enrollment: 130
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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 Műllerian 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

Primary outcomes:
measure: 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) in Mismatch Repair Proficient (pMMR) Participants
timeFrame: Up to approximately 45 months
measure: PFS Based on RECIST 1.1 as Assessed by BICR in All Randomized Participants
timeFrame: Up to approximately 45 months
measure: Overall Survival (OS) in pMMR Participants
timeFrame: Up to approximately 45 months
measure: OS in All Randomized Participants
timeFrame: Up to approximately 45 months
Secondary outcomes:
measure: Objective Response Rate (ORR) Based on RECIST 1.1 as Assessed by BICR in pMMR Participants
timeFrame: Up to approximately 45 months
measure: ORR Based on RECIST 1.1 as Assessed by BICR in All Randomized Participants
timeFrame: Up to approximately 45 months
measure: Mean Change From Baseline in the Global Health Status/Quality of Life Score of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) in pMMR Participants
timeFrame: Baseline and up to approximately 18 weeks
measure: Mean Change From Baseline in the Global Health Status/Quality of Life Score of the EORTC QLQ-C30 in All Randomized Participants
timeFrame: Baseline and up to approximately 18 weeks
measure: Percentage of Participants Experiencing an Adverse Event (AE)
timeFrame: Up to approximately 27 months (through 90 days after the last dose of study treatment)
measure: Percentage of Participants Experiencing a Serious Adverse Event (SAE)
timeFrame: Up to approximately 28 months (through 120 days after the last dose of study treatment)
measure: Percentage of Participants Experiencing an Immune-related AE (irAE)
timeFrame: Up to approximately 27 months (through 90 days after the last dose of study treatment)
measure: Percentage of Participants Discontinuing From Study Treatment Due to an AE(s)
timeFrame: Up to approximately 24 months (through the last dose of study treatment)
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Cancer Hospital-Gynecological Oncology ( Site 2509)
state: Anhui
city: Beijing
country: China
facility: Beijing Obstetrics and Gynecology Hospital Capital Medical University ( Site 2505)
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital ( Site 2501)
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital ( Site 2504)
state: Beijing
city: Chongqing
country: China
facility: Chongqing Cancer Hospital ( Site 2513)
state: Chongqing
city: Xiamen
country: China
facility: The First Affiliated hospital of Xiamen University-Obstetrics and gynecology department ( Site 2522)
state: Fujian
city: Guangzhou
country: China
facility: The First Affiliated Hospital.Sun Yat-sen University ( Site 2507)
state: Guangdong
city: Nanning
country: China
facility: Guang Xi Tumour Hospital, Department of Chemotherapy ( Site 2517)
state: Guangxi
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital ( Site 2520)
state: Heilongjiang
city: Wuhan
country: China
facility: Hubei Cancer Hospital ( Site 2510)
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital Central-South University ( Site 2512)
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital ( Site 2523)
state: Hunan
city: Nanjing
country: China
facility: Nanjing Maternity and Child Health Care Hospital ( Site 2508)
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Maternal and Child Health Hospital ( Site 2519)
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital Of Jilin University ( Site 2518)
state: Jilin
city: XI An
country: China
facility: The first affiliated Hospital of Xi an Jiaotong University ( Site 2502)
state: Shaanxi
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center ( Site 2500)
state: Shanghai
city: Shanghai
country: China
facility: Obstetrics and Gynecology Hosp. Fudan University ( Site 2503)
state: Shanghai
city: Shanghai
country: China
facility: Shanghai First Maternity and Infant Hospital ( Site 2524)
state: Shanghai
city: Urumqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University ( Site 2515)
state: Xinjiang
city: Hangzhou
country: China
facility: Women s Hospital School of Medicine Zhejiang University ( Site 2511)
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital ( Site 2506)
state: Zhejiang
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: