Clinical Trials List
Protocol NumberMK-7902-005 (E7080-G000-224)
NCT Number(ClinicalTrials.gov Identfier)NCT03797326
Completed
2020-12-01 - 2024-05-24
Phase II
Recruiting2
ICD-10C50.011
Malignant neoplasm of nipple and areola, right female breast
ICD-10C50.012
Malignant neoplasm of nipple and areola, left female breast
ICD-10C50.019
Malignant neoplasm of nipple and areola, unspecified female breast
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9174.0
Malignant neoplasm of female breast, nipple and areola
A Multicenter, Open-label Phase 2 Study of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) in Previously Treated Subjects With Selected Solid Tumors (LEAP-005)
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Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
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Sponsor
Merck Sharp & Dohme Corp.
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- Shang-Yin Wu Division of Hematology & Oncology
- 顏志傑 Division of Hematology & Oncology
- Chien-Jui Huang Division of General Internal Medicine
- Yu-Min Yeh Division of Hematology & Oncology
- 劉奕廷 Division of Hematology & Oncology
- Yan-Shen Shan Division of General Surgery
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Jih-Hsiang Lee Division of Hematology & Oncology
- 徐偉勛 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Advanced Solid Tumors, Triple Negative Breast Cancer, Ovarian Cancer, Gastric Cancer, Colorectal Cancer, Glioblastoma Biliary Tract Cancers, Pancreatic Cancer
Objectives
Primary:
1.Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Glioblastoma (GBM) by Investigator Assessment in Initial Cohorts
2.Percentage of Participants Receiving Pembrolizumab Plus Lenvatinib who Experience an Adverse Event (AE)
Secondary:
Disease Control Rate (DCR) per RECIST 1.1 by Investigator Assessment in Initial Cohorts
Duration of Response (DOR) per RECIST 1.1 or RANO (GBM) by Investigator Assessment in Initial Cohorts
Progression Free Survival (PFS) per RECIST 1.1 or RANO (GBM) by Investigator Assessment in Initial Cohort
Overall Survival (OS) in Initial Cohorts
Test Drug
LenvimaR capsules/KeytrudaR injection
Active Ingredient
Lenvatinib mesilate
Pembrolizumab
Pembrolizumab
Dosage Form
capsules
injection
injection
Dosage
4 mg或10 mg/capsule
100 mg/4 mL/vial
100 mg/4 mL/vial
Endpoints
Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Glioblastoma (GBM) by Investigator Assessment in Initial Cohorts
ORR per RECIST 1.1 or RANO (GBM) by Blinded Independent Central Review (BICR) in Expanded Cohorts (Combined with Initial Cohorts)
Percentage of Participants Receiving Pembrolizumab Plus Lenvatinib who Experience an Adverse Event (AE)
ORR per RECIST 1.1 or RANO (GBM) by Blinded Independent Central Review (BICR) in Expanded Cohorts (Combined with Initial Cohorts)
Percentage of Participants Receiving Pembrolizumab Plus Lenvatinib who Experience an Adverse Event (AE)
Inclution Criteria
Has a histologically or cytologically-documented, advanced (metastatic and/or unresectable) solid tumor that is incurable and for which prior standard systemic therapy has failed in one of the following cohorts: TNBC, Ovarian Cancer, Gastric Cancer, Colorectal Cancer, GBM, BTC (intrahepatic, extrahepatic cholangiocarcinoma and gall bladder cancer; excludes Ampulla of Vater), Pancreatic Cancer
Must have progressed on or since the last treatment
Has measurable disease per RECIST 1.1 (RANO for the GBM cohort) as assessed by the local site investigator/radiology and confirmed by BICR
Has provided a PD-L1 evaluable archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
Male participants agree to use approved contraception during the treatment period for at least 7 days after the last dose of lenvatinib, or refrain from heterosexual intercourse during this period
Female participants are not pregnant or breastfeeding, and are not a woman of childbearing potential (WOCBP), OR are a WOCBP that agrees to use contraception during the treatment period (or 14 days prior to the initiation of study treatment for oral contraception) and for at least 120 days post pembrolizumab, or 30 days post lenvatinib, whichever occurs last
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3 days of study treatment initiation
Has adequate organ function
For Triple Negative Breast Cancer Participants:
Has received one or 2 prior lines of therapy
Has Lactate Dehydrogenase (LDH) <2.0 x Upper Limit of Normal (ULN)
Has locally determined results for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 tumor analyses
For Ovarian Cancer Participants:
- Has received 3 prior lines of therapy. Note: The initial 30 participants in this cohort included participants with primary ovarian cancer. The expanded cohort will include participants with primary ovarian cancer, fallopian tube, and peritoneal ovarian cancer.
For Gastric Cancer Participants:
- Has received 2 prior lines of therapy. Note: Gastric cancer will include participants with both gastric and gastroesophageal junction (GEJ) adenocarcinoma. Participants with squamous cell carcinoma histology are not eligible
For Colorectal Cancer Participants:
- Has received 2 prior lines of therapy
For GBM Participants:
Has failed initial systemic therapy for newly diagnosed GBM
Have the following time periods elapsed before the projected start of scheduled study treatment: 1) at least 3 weeks from prior surgical resection, 2) at least 1 week from stereotactic biopsy, 3) at least 6 months from completion of prior radiotherapy, 4) at least 4 weeks (or 5 half-lives, whichever is shorter) from any investigational agent, 5) at least 4 weeks from cytotoxic therapy, 6) at least 6 weeks from antibodies, 7) at least 4 weeks (or 5 half-lives, whichever is shorter) from other antitumor therapies and 1 week for cancer vaccines
Be neurologically stable (e.g. without a progression of neurologic symptoms or requiring escalating doses of systemic steroid therapy within last 2 weeks) and clinically stable
Has histologically confirmed World Health Organization (WHO) Grade IV GBM
Has locally determined result for O^6-methylguanine-DNA methyltransferase (MGMT) analysis
For Biliary Tract Cancer Participants:
Has received 1 prior line of therapy
Child-Pugh Score, Class A: well-compensated disease. Child-Pugh Score of 5-6
For Pancreatic Cancer Participants:
Has pathologically (histologically or cytologically) confirmed pancreatic ductal adenocarcinoma that is metastatic at enrollment
Has received one or 2 prior lines of therapy
Has received prior therapy with at least 1 (platinum-containing regimen or gemcitabine-containing regimen) but no more than 2 prior systemic therapies for unresectable or metastatic pancreatic cancer
Must have progressed on or since the last treatment
Has measurable disease per RECIST 1.1 (RANO for the GBM cohort) as assessed by the local site investigator/radiology and confirmed by BICR
Has provided a PD-L1 evaluable archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
Male participants agree to use approved contraception during the treatment period for at least 7 days after the last dose of lenvatinib, or refrain from heterosexual intercourse during this period
Female participants are not pregnant or breastfeeding, and are not a woman of childbearing potential (WOCBP), OR are a WOCBP that agrees to use contraception during the treatment period (or 14 days prior to the initiation of study treatment for oral contraception) and for at least 120 days post pembrolizumab, or 30 days post lenvatinib, whichever occurs last
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3 days of study treatment initiation
Has adequate organ function
For Triple Negative Breast Cancer Participants:
Has received one or 2 prior lines of therapy
Has Lactate Dehydrogenase (LDH) <2.0 x Upper Limit of Normal (ULN)
Has locally determined results for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 tumor analyses
For Ovarian Cancer Participants:
- Has received 3 prior lines of therapy. Note: The initial 30 participants in this cohort included participants with primary ovarian cancer. The expanded cohort will include participants with primary ovarian cancer, fallopian tube, and peritoneal ovarian cancer.
For Gastric Cancer Participants:
- Has received 2 prior lines of therapy. Note: Gastric cancer will include participants with both gastric and gastroesophageal junction (GEJ) adenocarcinoma. Participants with squamous cell carcinoma histology are not eligible
For Colorectal Cancer Participants:
- Has received 2 prior lines of therapy
For GBM Participants:
Has failed initial systemic therapy for newly diagnosed GBM
Have the following time periods elapsed before the projected start of scheduled study treatment: 1) at least 3 weeks from prior surgical resection, 2) at least 1 week from stereotactic biopsy, 3) at least 6 months from completion of prior radiotherapy, 4) at least 4 weeks (or 5 half-lives, whichever is shorter) from any investigational agent, 5) at least 4 weeks from cytotoxic therapy, 6) at least 6 weeks from antibodies, 7) at least 4 weeks (or 5 half-lives, whichever is shorter) from other antitumor therapies and 1 week for cancer vaccines
Be neurologically stable (e.g. without a progression of neurologic symptoms or requiring escalating doses of systemic steroid therapy within last 2 weeks) and clinically stable
Has histologically confirmed World Health Organization (WHO) Grade IV GBM
Has locally determined result for O^6-methylguanine-DNA methyltransferase (MGMT) analysis
For Biliary Tract Cancer Participants:
Has received 1 prior line of therapy
Child-Pugh Score, Class A: well-compensated disease. Child-Pugh Score of 5-6
For Pancreatic Cancer Participants:
Has pathologically (histologically or cytologically) confirmed pancreatic ductal adenocarcinoma that is metastatic at enrollment
Has received one or 2 prior lines of therapy
Has received prior therapy with at least 1 (platinum-containing regimen or gemcitabine-containing regimen) but no more than 2 prior systemic therapies for unresectable or metastatic pancreatic cancer
Exclusion Criteria
Exclusion Criteria:
Has presence of gastrointestinal condition including malabsorption that might affect the absorption of lenvatinib
Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment (applies to all cohorts except the ovarian cancer cohort)
Has radiographic evidence of major blood vessel invasion/infiltration. Participants with portal vein invasion (Vp4), inferior vena cava, or cardiac involvement based on imaging in the BTC cohort are excluded
Has clinical significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study treatment
Has significant cardiovascular impairment within 12 months of the first dose of study treatment: such as history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident (CVA), or cardiac arrhythmia associated with hemodynamic instability
Has a history of arterial thromboembolism within 12 months of start of study treatment
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
Serious nonhealing wound, ulcer or bone fracture
Has had major surgery within 3 weeks prior to first dose of study interventions
Has biologic response modifiers (e.g. granulocyte colony-stimulating factor) within 4 weeks before study entry
Has preexisting ≥Grade 3 gastrointestinal (GI) or non-gastrointestinal fistula
Has received prior therapy with lenvatinib, an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Tumor necrosis factor receptor superfamily, member 4 [OX 40], tumor necrosis factor receptor superfamily member 9 [CD137])
Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to study treatment start
If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease
Has received a live vaccine within 30 days prior to the first dose of study treatment
Has known intolerance to lenvatinib (and/or any of the excipients)
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 the first dose of study treatment
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 the first dose of study treatment
Has known active CNS metastases and/or carcinomatous meningitis
Has tumors involving the brain stem
Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
Has an active autoimmune disease that has required systemic treatment in past 2 years
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
Has an active infection requiring systemic therapy
Has a known history of human immunodeficiency virus (HIV) infection
Has a known history of hepatitis B or known active hepatitis C virus infection
Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
Has had an allogenic tissue/solid organ transplant (large organ transplants, stem-cell transplant requiring chronic immunosuppressant therapy necessary to prevent graft rejection)
For GBM Participants:
Has carcinomatous meningitis
Has recurrent tumor greater than 6 cm in maximum diameter
Has tumor primarily localized to the brainstem or spinal cord
Has presence of multifocal tumor, diffuse leptomeningeal or extracranial disease
Has evidence of intratumoral or peritumoral hemorrhage on baseline magnetic resonance imaging (MRI) scan other than those that are grade ≤ 1 and either post-operative or stable on at least 2 consecutive MRI scans
Has received Optune® TTFields within 2 weeks of study intervention
Has presence of gastrointestinal condition including malabsorption that might affect the absorption of lenvatinib
Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment (applies to all cohorts except the ovarian cancer cohort)
Has radiographic evidence of major blood vessel invasion/infiltration. Participants with portal vein invasion (Vp4), inferior vena cava, or cardiac involvement based on imaging in the BTC cohort are excluded
Has clinical significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study treatment
Has significant cardiovascular impairment within 12 months of the first dose of study treatment: such as history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident (CVA), or cardiac arrhythmia associated with hemodynamic instability
Has a history of arterial thromboembolism within 12 months of start of study treatment
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
Serious nonhealing wound, ulcer or bone fracture
Has had major surgery within 3 weeks prior to first dose of study interventions
Has biologic response modifiers (e.g. granulocyte colony-stimulating factor) within 4 weeks before study entry
Has preexisting ≥Grade 3 gastrointestinal (GI) or non-gastrointestinal fistula
Has received prior therapy with lenvatinib, an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Tumor necrosis factor receptor superfamily, member 4 [OX 40], tumor necrosis factor receptor superfamily member 9 [CD137])
Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to study treatment start
If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease
Has received a live vaccine within 30 days prior to the first dose of study treatment
Has known intolerance to lenvatinib (and/or any of the excipients)
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 the first dose of study treatment
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 the first dose of study treatment
Has known active CNS metastases and/or carcinomatous meningitis
Has tumors involving the brain stem
Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
Has an active autoimmune disease that has required systemic treatment in past 2 years
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
Has an active infection requiring systemic therapy
Has a known history of human immunodeficiency virus (HIV) infection
Has a known history of hepatitis B or known active hepatitis C virus infection
Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
Has had an allogenic tissue/solid organ transplant (large organ transplants, stem-cell transplant requiring chronic immunosuppressant therapy necessary to prevent graft rejection)
For GBM Participants:
Has carcinomatous meningitis
Has recurrent tumor greater than 6 cm in maximum diameter
Has tumor primarily localized to the brainstem or spinal cord
Has presence of multifocal tumor, diffuse leptomeningeal or extracranial disease
Has evidence of intratumoral or peritumoral hemorrhage on baseline magnetic resonance imaging (MRI) scan other than those that are grade ≤ 1 and either post-operative or stable on at least 2 consecutive MRI scans
Has received Optune® TTFields within 2 weeks of study intervention
The Estimated Number of Participants
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Taiwan
20 participants
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Global
600 participants
