Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Versus Chemotherapy for Endometrial Carcinoma (ENGOT-en9 / MK-7902-001) - China Extension Study
- Conditions
- Endometrial Neoplasms
- Interventions
- Registration Number
- NCT04865289
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 130
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lenvatinib + Pembrolizumab Lenvatinib Participants receive lenvatinib daily and pembrolizumab once at the start of each 3-week treatment cycle. Paclitaxel + Carboplatin Paclitaxel Participants receive paclitaxel and carboplatin once at the start of each 3-week treatment cycle. Paclitaxel + Carboplatin Carboplatin Participants receive paclitaxel and carboplatin once at the start of each 3-week treatment cycle. Lenvatinib + Pembrolizumab Pembrolizumab Participants receive lenvatinib daily and pembrolizumab once at the start of each 3-week treatment cycle.
- Primary Outcome Measures
Name Time Method 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 Up to approximately 45 months PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS of pMMR participants was presented.
PFS Based on RECIST 1.1 as Assessed by BICR in All Randomized Participants Up to approximately 45 months PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS of all randomized participants was presented.
Overall Survival (OS) in pMMR Participants Up to approximately 45 months OS was measured from the time of randomization up to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The OS for pMMR participants is presented.
OS in All Randomized Participants Up to approximately 45 months OS was measured from the time of randomization up to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The OS for all randomized participants is presented.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) Based on RECIST 1.1 as Assessed by BICR in pMMR Participants Up to approximately 45 months ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1. The percentage of pMMR participants who experienced a CR or PR is presented.
ORR Based on RECIST 1.1 as Assessed by BICR in All Randomized Participants Up to approximately 45 months ORR was defined as the percentage of participants who had a CR: Disappearance of all target lesions or a PR: At least a 30% decrease in the sum of diameters of target lesions as assessed using RECIST 1.1. The percentage of all randomized participants who experienced a CR or PR is presented.
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 Baseline and up to approximately 18 weeks 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.
Mean Change From Baseline in the Global Health Status/Quality of Life Score of the EORTC QLQ-C30 in All Randomized Participants Baseline and up to approximately 18 weeks 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 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.
Percentage of Participants Experiencing an Adverse Event (AE) Up to approximately 27 months (through 90 days after the last dose of study treatment) 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.
Percentage of Participants Experiencing a Serious Adverse Event (SAE) Up to approximately 28 months (through 120 days after the last dose of study treatment) 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.
Percentage of Participants Experiencing an Immune-related AE (irAE) Up to approximately 27 months (through 90 days after the last dose of study treatment) Immune-related AEs will be monitored in both arms.
Percentage of Participants Discontinuing From Study Treatment Due to an AE(s) Up to approximately 24 months (through the last dose of study treatment) Discontinuations related to AEs will be monitored in both arms.
Trial Locations
- Locations (22)
Fudan University Shanghai Cancer Center ( Site 2500)
🇨🇳Shanghai, Shanghai, China
Women s Hospital School of Medicine Zhejiang University ( Site 2511)
🇨🇳Hangzhou, Zhejiang, China
Anhui Cancer Hospital-Gynecological Oncology ( Site 2509)
🇨🇳Hefei, Anhui, China
Beijing Obstetrics and Gynecology Hospital Capital Medical University ( Site 2505)
🇨🇳Beijing, Beijing, China
Peking Union Medical College Hospital ( Site 2501)
🇨🇳Beijing, Beijing, China
Beijing Cancer Hospital ( Site 2504)
🇨🇳Beijing, Beijing, China
Guang Xi Tumour Hospital, Department of Chemotherapy ( Site 2517)
🇨🇳Nanning, Guangxi, China
The First Affiliated Hospital.Sun Yat-sen University ( Site 2507)
🇨🇳Guangzhou, Guangdong, China
Chongqing Cancer Hospital ( Site 2513)
🇨🇳Chongqing, Chongqing, China
The First Affiliated hospital of Xiamen University-Obstetrics and gynecology department ( Site 2522)
🇨🇳Xiamen, Fujian, China
Harbin Medical University Cancer Hospital ( Site 2520)
🇨🇳Harbin, Heilongjiang, China
Hubei Cancer Hospital ( Site 2510)
🇨🇳Wuhan, Hubei, China
Xiangya Hospital Central-South University ( Site 2512)
🇨🇳Changsha, Hunan, China
Hunan Cancer Hospital ( Site 2523)
🇨🇳Changsha, Hunan, China
Jiangxi Maternal and Child Health Hospital ( Site 2519)
🇨🇳Nanchang, Jiangxi, China
The first affiliated Hospital of Xi an Jiaotong University ( Site 2502)
🇨🇳XI An, Shaanxi, China
Nanjing Maternity and Child Health Care Hospital ( Site 2508)
🇨🇳Nanjing, Jiangsu, China
The First Hospital Of Jilin University ( Site 2518)
🇨🇳Changchun, Jilin, China
The First Affiliated Hospital of Xinjiang Medical University ( Site 2515)
🇨🇳Urumqi, Xinjiang, China
Obstetrics and Gynecology Hosp. Fudan University ( Site 2503)
🇨🇳Shanghai, Shanghai, China
Shanghai First Maternity and Infant Hospital ( Site 2524)
🇨🇳Shanghai, Shanghai, China
Zhejiang Cancer Hospital ( Site 2506)
🇨🇳Hangzhou, Zhejiang, China