Endometrial Neoplasms
Conditions
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.
Interventions
DRUGLenvatinib
Lenvatinib 4 mg or 10 mg capsules at a total daily dose of 20 mg taken by mouth once per day.
BIOLOGICALPembrolizumab
Pembrolizumab 200 mg intravenous (IV) infusion given on Day 1 of each cycle.
DRUGPaclitaxel
Paclitaxel 175 mg/m\^2 IV infusion given on Day 1 of each cycle.
DRUGCarboplatin
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.
Sponsors
Merck Sharp & Dohme LLC
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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 Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (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 at ≥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 or 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 (HCV) \[defined as HCV ribonucleic acid (RNA) is detected\] (hepatitis B and C testing is required at screening only when mandated by local health authority) * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 44 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 44 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 51 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 51 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
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Based on RECIST 1.1 as Assessed by BICR in pMMR Participants | Up to approximately 51 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 51 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. |
| Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 68 months | An AE was 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. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated). Per protocol, the number of participants who experienced one or more AEs was reported for the first course lenvatinib + pembrolizumab and paclitaxel + carboplatin arms. |
| Number of Participants Who Experienced a Serious Adverse Event (SAE) | Up to approximately 68 months | An SAE was an AE that resulted in death, was life-threatening, required or prolonged hospitalization, resulted in persistent or significant disability, was a congenital birth defect, or was another important medical event. Per protocol, the number of participants who experienced one or more SAEs was reported for the first course lenvatinib + pembrolizumab and paclitaxel + carboplatin arms. |
| Number of Participants Who Experienced an Immune-Related Adverse Event (irAE) | Up to approximately 68 months | 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. Immune-related AEs (irAEs) were AEs that were considered immune-mediated or potentially immune-mediated and are well-documented for pembrolizumab. These irAEs may occur shortly after the first dose or several months after the last dose of pembrolizumab treatment and may affect more than one body system simultaneously. Per protocol, the number of participants who experienced one or more irAEs was reported for the first course lenvatinib + pembrolizumab and paclitaxel + carboplatin arms. |
| Number of Participants Who Discontinued Study Intervention Due to an AE | Up to approximately 68 months | An AE was 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. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated). Per protocol, the number of participants who discontinued any study intervention (pembrolizumab and/or lenvatinib or paclitaxel and/or carboplatin) due to an AE was reported for the first course lenvatinib + pembrolizumab and paclitaxel + carboplatin arms. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Germany, Ireland, Israel, Italy, Japan, Mexico, Poland, Russia, South Korea, Spain, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Recruitment details
Of the 842 total participants randomized in the MK-7902-001 global study, 66 were also randomized in the China extension study for MK-7902-001 (NCT04865289).
Pre-assignment details
Per protocol, response/progression or adverse events (AEs) that occurred during the second course were not counted towards efficacy outcome measures or safety outcome measures, respectively.
Participants by arm
| Arm | Count |
|---|---|
| Lenvatinib + Pembrolizumab Participants received lenvatinib daily and pembrolizumab once at the start of each 3-week treatment cycle. | 420 |
| Paclitaxel + Carboplatin Participants received paclitaxel and carboplatin once at the start of each 3-week treatment cycle. | 422 |
| Total | 842 |
Baseline characteristics
| Characteristic | Lenvatinib + Pembrolizumab | Total | Paclitaxel + Carboplatin |
|---|---|---|---|
| Age, Continuous | 62.5 Years STANDARD_DEVIATION 10.1 | 63.3 Years STANDARD_DEVIATION 9.7 | 64.0 Years STANDARD_DEVIATION 9.1 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG=0 | 250 Participants | 490 Participants | 240 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG=1 | 170 Participants | 352 Participants | 182 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 64 Participants | 131 Participants | 67 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 347 Participants | 690 Participants | 343 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants | 21 Participants | 12 Participants |
| Mismatch Repair (MMR) Status dMMR | 100 Participants | 200 Participants | 100 Participants |
| Mismatch Repair (MMR) Status pMMR | 320 Participants | 642 Participants | 322 Participants |
| Prior Chemotherapy and/or Chemoradiation No | 346 Participants | 700 Participants | 354 Participants |
| Prior Chemotherapy and/or Chemoradiation Yes | 74 Participants | 142 Participants | 68 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 114 Participants | 216 Participants | 102 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 24 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 8 Participants | 13 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 288 Participants | 588 Participants | 300 Participants |
| Sex: Female, Male Female | 420 Participants | 842 Participants | 422 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 233 / 420 | 253 / 422 | 3 / 17 |
| other Total, other adverse events | 416 / 420 | 397 / 411 | 15 / 17 |
| serious Total, serious adverse events | 230 / 420 | 84 / 411 | 3 / 17 |
Outcome results
Primary
OS in All Randomized Participants
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.
Time frame: Up to approximately 51 months
Population: All randomized participants were analyzed according to the treatment arm to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenvatinib + Pembrolizumab | OS in All Randomized Participants | 37.7 Months |
| Paclitaxel + Carboplatin | OS in All Randomized Participants | 32.1 Months |
p-value: 0.2155295% CI: [0.77, 1.12]Log Rank
Primary
Overall Survival (OS) in pMMR Participants
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.
Time frame: Up to approximately 51 months
Population: All randomized pMMR participants were analyzed according to the treatment arm to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenvatinib + Pembrolizumab | Overall Survival (OS) in pMMR Participants | 30.9 Months |
| Paclitaxel + Carboplatin | Overall Survival (OS) in pMMR Participants | 29.4 Months |
p-value: 0.245987595% CI: [0.83, 1.26]Log Rank
p-value: 0.587559795% CI: [0.83, 1.26]Log Rank
Primary
PFS Based on RECIST 1.1 as Assessed by BICR in All Randomized Participants
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.
Time frame: Up to approximately 44 months
Population: All randomized participants were analyzed according to the treatment arm to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenvatinib + Pembrolizumab | PFS Based on RECIST 1.1 as Assessed by BICR in All Randomized Participants | 12.5 Months |
| Paclitaxel + Carboplatin | PFS Based on RECIST 1.1 as Assessed by BICR in All Randomized Participants | 10.2 Months |
p-value: 0.179205895% CI: [0.77, 1.1]Log Rank
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) in Mismatch Repair Proficient (pMMR) Participants
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.
Time frame: Up to approximately 44 months
Population: All randomized pMMR participants were analyzed according to the treatment arm to which they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lenvatinib + Pembrolizumab | 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 | 9.6 Months |
| Paclitaxel + Carboplatin | 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 | 10.2 Months |
p-value: 0.555012195% CI: [0.83, 1.24]Log Rank
Secondary
Mean Change From Baseline in the Global Health Status/Quality of Life Score of the EORTC QLQ-C30 in All Randomized 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 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.
Time frame: Baseline and up to approximately 18 weeks
Population: All randomized participants who had at least one assessment available for EORTC QLQ-C30 and received at least one dose of the study intervention were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Lenvatinib + Pembrolizumab | Mean Change From Baseline in the Global Health Status/Quality of Life Score of the EORTC QLQ-C30 in All Randomized Participants | -4.52 Scores on a scale |
| Paclitaxel + Carboplatin | Mean Change From Baseline in the Global Health Status/Quality of Life Score of the EORTC QLQ-C30 in All Randomized Participants | -2.22 Scores on a scale |
p-value: 0.135595% CI: [-5.31, 0.72]cLDA model
Secondary
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
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.
Time frame: Baseline and up to approximately 18 weeks
Population: All randomized pMMR participants who had at least one assessment available for EORTC QLQ-C30 and received at least one dose of the study intervention were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Lenvatinib + Pembrolizumab | 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 | -5.10 Scores on a scale |
| Paclitaxel + Carboplatin | 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 | -1.34 Scores on a scale |
p-value: 0.030295% CI: [-7.17, -0.36]cLDA model
Secondary
Objective Response Rate (ORR) Based on RECIST 1.1 as Assessed by BICR in pMMR Participants
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.
Time frame: Up to approximately 51 months
Population: Per protocol, all randomized pMMR participants with measurable disease at the baseline scan were analyzed according to the treatment arm to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lenvatinib + Pembrolizumab | Objective Response Rate (ORR) Based on RECIST 1.1 as Assessed by BICR in pMMR Participants | 50.9 Percentage of Participants |
| Paclitaxel + Carboplatin | Objective Response Rate (ORR) Based on RECIST 1.1 as Assessed by BICR in pMMR Participants | 55.2 Percentage of Participants |
p-value: 0.856995% CI: [-11.9, 3.5]Stratified Miettinen & Nurminen
Secondary
ORR Based on RECIST 1.1 as Assessed by BICR in All Randomized Participants
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.
Time frame: Up to approximately 51 months
Population: Per protocol, all randomized participants with measurable disease at the baseline scan were analyzed according to the treatment arm to which they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lenvatinib + Pembrolizumab | ORR Based on RECIST 1.1 as Assessed by BICR in All Randomized Participants | 56.0 Percentage of Participants |
| Paclitaxel + Carboplatin | ORR Based on RECIST 1.1 as Assessed by BICR in All Randomized Participants | 56.0 Percentage of Participants |
p-value: 0.499995% CI: [-6.7, 6.7]Stratified Miettinen & Nurminen
Secondary
Percentage of Participants Discontinuing From Study Treatment Due to an AE(s)
Discontinuations related to AEs will be monitored in both arms.
Time frame: Up to approximately 24 months (through the last dose of study treatment)
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.
Time frame: Up to approximately 27 months (through 90 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.
Time frame: 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.
Time frame: Up to approximately 28 months (through 120 days after the last dose of study treatment)