NCT03797326 · REGISTRY CONDITION SEARCH

Efficacy and Safety of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) in Previously Treated Participants With Select Solid Tumors (MK-7902-005/E7080-G000-224/LEAP-005)

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE2
Status at capture: COMPLETED
Registry last update: 2026-05-04

The purpose of this study is to determine the safety and efficacy of combination therapy with pembrolizumab (MK-3475) and lenvatinib (E7080/MK-7902) in participants with triple negative breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (CRC), glioblastoma (GBM), biliary tract cancers (BTC), or pancreatic cancer.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

→

baseline

Baseline characteristics

→

outcome · POSTED

Disease Control Rate (DCR) Per RECIST 1.1 by Investigator Assessment

→

outcome · POSTED

Disease Control Rate (DCR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR

→

outcome · POSTED

Duration of Response (DOR) Per RECIST 1.1 by Investigator Assessment

→

outcome · POSTED

Duration of Response (DOR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR

→

outcome · POSTED

Progression-Free Survival (PFS) Per RECIST 1.1 by Investigator Assessment

→

outcome · POSTED

Progression-Free Survival (PFS) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR

→

outcome · POSTED

Overall Survival (OS)

→

outcome · POSTED

Area Under the Concentration Curve at Steady State (AUCss) of Lenvatinib

→

outcome · POSTED

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Investigator Assessment

→

outcome · POSTED

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 Multiforma [GBM] Only), by Blinded Independent Central Review (BICR)

→

outcome · POSTED

Number of Participants With One or More Adverse Events (AEs)

→

outcome · POSTED

Number of Participants Who Discontinued From Study Treatment Due to an AE

→

adverse events

Adverse events

→

more info

Limitations, agreements, and source contact

→

Who could take part

eligibility Criteria: Inclusion 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 primary ovarian cancer and has received 3 prior lines of therapy. 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: * Has gastrointestinal malabsorption or any other condition 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 encasement or invasion of a major blood vessel or of intratumoral cavitation. Participants with portal vein invasion (Vp4), inferior vena cava, or cardiac involvement based on imaging in the BTC cohort are not eligible for enrollment * 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. * Has a 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 therapy (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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) plus lenvatinib 20 mg via oral capsule once a day (QD). Pembrolizumab will be administered for up to 35 cycles (up to 2 years). Lenvatinib will be administered until progressive disease or unacceptable toxicity (up to at least 2 years).
intervention Names
Biological: Pembrolizumab
Drug: Lenvatinib
label
Pembrolizumab + Lenvatinib (Arm 1)
type
EXPERIMENTAL
description
Participants receive lenvatinib 24 mg via oral capsule QD, to be administered until progressive disease or unacceptable toxicity (up to at least 2 years).
intervention Names
Drug: Lenvatinib
label
Lenvatinib Monotherapy (Arm 2)
type
EXPERIMENTAL

interventions

arm Group Labels
Pembrolizumab + Lenvatinib (Arm 1)
description
Administered as an IV infusion on Day 1 Q3W.
name
Pembrolizumab
other Names
MK-3475
Keytruda®
type
BIOLOGICAL
arm Group Labels
Lenvatinib Monotherapy (Arm 2)
Pembrolizumab + Lenvatinib (Arm 1)
description
Administered orally once a day during each 21-day cycle.
name
Lenvatinib
other Names
MK-7902
E7080
LENVIMA™
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 611
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
ORR was defined as the percentage of participants who had a best overall response of either Complete Response (CR): Disappearance of all target lesions or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions as assessed by RECIST 1.1. The percentage of participants who experienced a CR or PR as assessed by RECIST 1.1 by investigator assessment was presented. Per protocol, only data for Cohorts A and B were presented for this endpoint.
measure
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Investigator Assessment
time Frame
Up to approximately 66 months
description
ORR was defined as the percentage of participants who had a best overall response of either Complete Response (CR): Disappearance of all target lesions or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions as assessed by RECIST 1.1. For participants with GBM, response was assessed according to RANO criteria whereby ORR was defined as the percentage of participants who had a best overall response of either Complete response (CR): Disappearance of all target lesions or Partial response (PR): sum of products of diameters decreased by ≥50% from baseline value. The percentage of participants who experienced a CR or PR as assessed by RECIST 1.1 or RANO by BICR was presented. Per protocol, only data for Cohorts C, D1, D2, E, F, and G were presented for this endpoint.
measure
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 Multiforma [GBM] Only), by Blinded Independent Central Review (BICR)
time Frame
Up to approximately 66 months
description
An AE was defined as 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 can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants with at least one or more AE is presented.
measure
Number of Participants With One or More Adverse Events (AEs)
time Frame
Up to approximately 66 months
description
An AE was defined as 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 can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued from study treatment due to an AE is presented.
measure
Number of Participants Who Discontinued From Study Treatment Due to an AE
time Frame
Up to approximately 62 months

secondary Outcomes

description
DCR was defined per RECIST 1.1 as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD\]). Disease Control rate per RECIST 1.1 by investigator assessment is presented. Per protocol, only data for Cohorts A and B were presented for this endpoint.
measure
Disease Control Rate (DCR) Per RECIST 1.1 by Investigator Assessment
time Frame
Up to approximately 66 months
description
DCR was defined per RECIST 1.1 as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm\]). The appearance of one or more new lesions is also considered PD.\]). For participants with GBM, response was assessed according to RANO criteria whereby overall response was based on both radiographic response (CR: disappearance of all target lesions, PR: sum of products of diameters \[SPD\] decreased by ≥ 50% from baseline value and SD: SPD \<50% decreased from baseline, but \<25% increased from nadir) and clinical performance status with steroid dose information. The DCR as assessed by BICR is presented.
measure
Disease Control Rate (DCR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR
time Frame
Up to approximately 66 months
description
For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. Duration of response per RECIST 1.1 by investigator assessment is presented. Per protocol, only data for Cohorts A and B were presented for this endpoint.
measure
Duration of Response (DOR) Per RECIST 1.1 by Investigator Assessment
time Frame
Up to approximately 66 months
description
For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. For participants with GBM, response will be assessed according to RANO criteria whereby overall RANO response is based on both radiographic response (CR: disappearance of all target lesions, PR: SPD decreased by ≥ 50% from baseline value) and clinical performance status with steroid dose information. DOR assessments were based on blinded central imaging review with confirmation.
measure
Duration of Response (DOR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR
time Frame
Up to approximately 66 months
description
PFS was defined as the time from date of study treatment to the first documented progressive disease (PD) based on RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ 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 must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The percentage of participants who experienced PFS per RECIST 1.1 by investigator assessment is presented. Per protocol, only data for Cohorts A and B were presented for this endpoint.
measure
Progression-Free Survival (PFS) Per RECIST 1.1 by Investigator Assessment
time Frame
Up to approximately 66 months
description
PFS was defined as the time from date of study treatment to the first documented progressive disease (PD) based on RECIST 1.1 (or RANO for GBM participants), modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ 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 must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. For participants with GBM, either radiological progression or clinical deterioration (not attributable to a nontumor-related cause) qualifies as PD. The percentage of participants who experienced PFS per RECIST 1.1 or RANO by BICR is presented. Per protocol, only data for Cohorts C, D1, D2, E, F, and G were presented for this endpoint.
measure
Progression-Free Survival (PFS) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR
time Frame
Up to approximately 66 months
description
OS was defined as the time from the date of study treatment to the date of death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. The OS for all participants is presented.
measure
Overall Survival (OS)
time Frame
Up to approximately 66 months
description
Blood samples were collected at pre-specified timepoints to determine the AUCss in participants receiving Lenvatinib (Lenva) co-administered with Pembrolizumab (Pembro). AUCss was defined as a measure of drug exposure that was calculated as the product of plasma drug concentration and time after drug administration at steady state. AUCss determined by blood samples collected pre-dose and at designated timepoints post-dose are presented. Noncompartmental analysis was used to calculate AUC0ss for each participant. Mean and standard deviation of AUCss were calculated for each cohort. As specified in the protocol, pharmacokinetic analysis was not planned or conducted in Cohorts D2 and G.
measure
Area Under the Concentration Curve at Steady State (AUCss) of Lenvatinib
time Frame
Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose and 2-12 hours post-dose; Cycle 2 Day 1: pre-dose, 0.5-4 hours, and 6-10 hours post-dose (up to approximately 23 days). Each cycle is 21 days.

Full study description

brief Summary: The purpose of this study is to determine the safety and efficacy of combination therapy with pembrolizumab (MK-3475) and lenvatinib (E7080/MK-7902) in participants with triple negative breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (CRC), glioblastoma (GBM), biliary tract cancers (BTC), or pancreatic cancer.

Source references

references

citation
Gonzalez-Martin A, Chung HC, Saada-Bouzid E, Yanez E, Senellart H, Cassier PA, Basu B, Corr BR, Girda E, Dutcus C, Okpara CE, Ghori R, Jin F, Groisberg R, Lwin Z. Lenvatinib plus pembrolizumab for patients with previously treated advanced ovarian cancer: Results from the phase 2 multicohort LEAP-005 study. Gynecol Oncol. 2024 Jul;186:182-190. doi: 10.1016/j.ygyno.2024.04.011. Epub 2024 May 7.
pmid
38718741
type
RESULT
citation
Chung HC, Saada-Bouzid E, Longo F, Yanez E, Im SA, Castanon E, Desautels DN, Graham DM, Garcia-Corbacho J, Lopez J, Dutcus C, Okpara CE, Ghori R, Jin F, Groisberg R, Korakis I. Lenvatinib plus pembrolizumab for patients with previously treated, advanced, triple-negative breast cancer: Results from the triple-negative breast cancer cohort of the phase 2 LEAP-005 Study. Cancer. 2024 Oct 1;130(19):3278-3288. doi: 10.1002/cncr.35387. Epub 2024 Jun 21.
pmid
39031824
type
RESULT
citation
Ponz-Sarvise M, Rha SY, Gomez-Roca CA, Ortega Moran L, Gill S, Tortora G, Geva R, Saada-Bouzid E, Santoro A, Kim TW, Heudobler D, Dutcus CE, Okpara CE, Ghori R, Zhang Y, Vajdi A, Dettman EJ, Jin F, Groisberg R, Shapira-Frommer R. Lenvatinib plus Pembrolizumab for Patients with Previously Treated Advanced Gastric, Biliary Tract, or Pancreatic Cancer: Results from the Phase II LEAP-005 Study. Cancer Res Commun. 2026 Mar 1;6(3):673-686. doi: 10.1158/2767-9764.CRC-26-0018.
pmid
41747221
type
RESULT
citation
Victoria Ruiz I, Uboha NV, Jamal R, Mejia FC, Ahumada M, Im SA, Gomez-Roca C, Shapira-Frommer R, Perets R, Yanez E, Dutcus C, Okpara CE, Ghori R, Jin F, Groisberg R, Castanon E. Lenvatinib Plus Pembrolizumab for Patients With Previously Treated Advanced Colorectal Cancer: Results From the Phase II LEAP-005 Study. Clin Colorectal Cancer. 2026 Jun;25(2):225-238.e2. doi: 10.1016/j.clcc.2026.01.003. Epub 2026 Jan 22.
pmid
41763955
type
DERIVED
citation
Rha SY, Castanon E, Gill S, Senellart H, Lopez J, Marquez-Rodas I, Victoria I, Kim TM, Lwin Z, Burger MC, Simonelli M, Cassier PA, Hendifar AE, Ascierto PA, Dutcus C, Okpara CE, Ghori R, Jin F, Groisberg R, Villanueva L. Lenvatinib plus pembrolizumab for patients with previously treated select solid tumors: Results from the phase 2 LEAP-005 study recurrent glioblastoma cohort. Cancer. 2025 Aug 15;131(16):e70015. doi: 10.1002/cncr.70015.
pmid
40808295
type
DERIVED