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NCT03797326

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)

Completed Phase 2 Results posted Last updated 17 November 2025
What this trial tests

Phase 2 trial testing Pembrolizumab in Advanced Solid Tumors in 611 participants. Completed in 28 October 2024.

Timeline
12 February 2019
Primary endpoint
28 October 2024
28 October 2024

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment611
Start date12 February 2019
Primary completion28 October 2024
Estimated completion28 October 2024
Sites88 locations across France, Colombia, Italy, Russia, Chile, Taiwan, United Kingdom, Germany

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Advanced Solid Tumors or Triple Negative Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Disease Control Rate (DCR) Per RECIST 1.1 by Investigator Assessment Secondary · Up to approximately 66 months

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 assessme

GroupValue95% CI
Cohort A: Triple Negative Breast Cancer (Lenva + Pembro)51.633.1 – 69.8
Cohort B: Ovarian Cancer (Lenva + Pembro)77.458.9 – 90.4
Disease Control Rate (DCR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR Secondary · Up to approximately 66 months

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 accordi

GroupValue95% CI
Cohort C: Gastric Cancer (Lenva + Pembro)53.543.2 – 63.6
Cohort D1: Colorectal Cancer (Lenva + Pembro)52.442.4 – 62.2
Cohort D2: Colorectal Cancer (Lenva)56.737.4 – 74.5
Cohort E: Glioblastoma Multiforma (Lenva + Pembro)57.447.2 – 67.2
Cohort F: Biliary Tract Cancer (Lenva + Pembro)64.754.6 – 73.9
Cohort G: Pancreatic Cancer (Lenva + Pembro)37.928.5 – 48.0
Duration of Response (DOR) Per RECIST 1.1 by Investigator Assessment Secondary · Up to approximately 66 months

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

GroupValue95% CI
Cohort A: Triple Negative Breast Cancer (Lenva + Pembro)22.94.2 – NA
Cohort B: Ovarian Cancer (Lenva + Pembro)15.36.4 – NA
Duration of Response (DOR) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR Secondary · Up to approximately 66 months

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

GroupValue95% CI
Cohort C: Gastric Cancer (Lenva + Pembro)8.34.2 – NA
Cohort D1: Colorectal Cancer (Lenva + Pembro)8.34.2 – 18.5
Cohort D2: Colorectal Cancer (Lenva)NANA – NA
Cohort E: Glioblastoma Multiforma (Lenva + Pembro)4.63.2 – 15.6
Cohort F: Biliary Tract Cancer (Lenva + Pembro)6.24.2 – 7.1
Cohort G: Pancreatic Cancer (Lenva + Pembro)5.82.7 – NA
Progression-Free Survival (PFS) Per RECIST 1.1 by Investigator Assessment Secondary · Up to approximately 66 months

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 RE

GroupValue95% CI
Cohort A: Triple Negative Breast Cancer (Lenva + Pembro)4.21.7 – 6.3
Cohort B: Ovarian Cancer (Lenva + Pembro)6.14.1 – 9.4
Progression-Free Survival (PFS) Per RECIST 1.1 or RANO Criteria (GBM Only) by BICR Secondary · Up to approximately 66 months

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,

GroupValue95% CI
Cohort C: Gastric Cancer (Lenva + Pembro)3.52.3 – 4.1
Cohort D1: Colorectal Cancer (Lenva + Pembro)3.42.1 – 4.1
Cohort D2: Colorectal Cancer (Lenva)3.42.1 – 4.8
Cohort E: Glioblastoma Multiforma (Lenva + Pembro)3.02.8 – 4.1
Cohort F: Biliary Tract Cancer (Lenva + Pembro)4.13.6 – 5.9
Cohort G: Pancreatic Cancer (Lenva + Pembro)2.12.1 – 3.1
Overall Survival (OS) Secondary · Up to approximately 66 months

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.

GroupValue95% CI
Cohort A: Triple Negative Breast Cancer (Lenva + Pembro)11.44.1 – 21.7
Cohort B: Ovarian Cancer (Lenva + Pembro)21.311.7 – 32.3
Cohort C: Gastric Cancer (Lenva + Pembro)4.73.8 – 6.1
Cohort D1: Colorectal Cancer (Lenva + Pembro)8.77.0 – 10.0
Cohort D2: Colorectal Cancer (Lenva)7.95.6 – 14.9
Cohort E: Glioblastoma Multiforma (Lenva + Pembro)8.67.4 – 10.8
Cohort F: Biliary Tract Cancer (Lenva + Pembro)7.95.6 – 9.5
Cohort G: Pancreatic Cancer (Lenva + Pembro)4.33.8 – 5.4
Area Under the Concentration Curve at Steady State (AUCss) of Lenvatinib Secondary · 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.

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

GroupValue95% CI
Cohort A: Triple Negative Breast Cancer (Lenva + Pembro)3253± 1029
Cohort B: Ovarian Cancer (Lenva + Pembro)3145± 984
Cohort C: Gastric Cancer (Lenva + Pembro)2392± 803
Cohort D1: Colorectal Cancer (Lenva + Pembro)2994± 1143
Cohort E: Glioblastoma Multiforma (Lenva + Pembro)2617± 804
Cohort F: Biliary Tract Cancer (Lenva + Pembro)2886± 838
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Investigator Assessment Primary · Up to approximately 66 months

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.

GroupValue95% CI
Cohort A: Triple Negative Breast Cancer (Lenva + Pembro)22.69.6 – 41.1
Cohort B: Ovarian Cancer (Lenva + Pembro)25.811.9 – 44.6
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) Primary · Up to approximately 66 months

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.

GroupValue95% CI
Cohort C: Gastric Cancer (Lenva + Pembro)15.28.7 – 23.8
Cohort D1: Colorectal Cancer (Lenva + Pembro)14.38.2 – 22.5
Cohort D2: Colorectal Cancer (Lenva)6.70.8 – 22.1
Cohort E: Glioblastoma Multiforma (Lenva + Pembro)21.814.2 – 31.1
Cohort F: Biliary Tract Cancer (Lenva + Pembro)17.610.8 – 26.4
Cohort G: Pancreatic Cancer (Lenva + Pembro)7.83.4 – 14.7
Number of Participants With One or More Adverse Events (AEs) Primary · Up to approximately 66 months

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.

GroupValue95% CI
Cohort A: Triple Negative Breast Cancer (Lenva + Pembro)31
Cohort B: Ovarian Cancer (Lenva + Pembro)31
Cohort C: Gastric Cancer (Lenva + Pembro)97
Cohort D1: Colorectal Cancer (Lenva + Pembro)104
Cohort D2: Colorectal Cancer (Lenva)30
Cohort E: Glioblastoma Multiforma (Lenva + Pembro)101
Cohort F: Biliary Tract Cancer (Lenva + Pembro)102
Cohort G: Pancreatic Cancer (Lenva + Pembro)103
Number of Participants Who Discontinued From Study Treatment Due to an AE Primary · Up to approximately 62 months

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.

GroupValue95% CI
Cohort A: Triple Negative Breast Cancer (Lenva + Pembro)5
Cohort B: Ovarian Cancer (Lenva + Pembro)11
Cohort C: Gastric Cancer (Lenva + Pembro)23
Cohort D1: Colorectal Cancer (Lenva + Pembro)19
Cohort D2: Colorectal Cancer (Lenva)4
Cohort E: Glioblastoma Multiforma (Lenva + Pembro)11
Cohort F: Biliary Tract Cancer (Lenva + Pembro)20
Cohort G: Pancreatic Cancer (Lenva + Pembro)19

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 66 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort A: Triple Negative Breast Cancer (Lenva + Pembro)
Serious: 16/31 (52%)
Deaths: 27/31
Cohort B: Ovarian Cancer (Lenva + Pembro)
Serious: 19/31 (61%)
Deaths: 28/31
Cohort C: Gastric Cancer (Lenva + Pembro)
Serious: 57/99 (58%)
Deaths: 97/102
Cohort D1: Colorectal Cancer (Lenva + Pembro)
Serious: 55/105 (52%)
Deaths: 97/107
Cohort D2: Colorectal Cancer (Lenva)
Serious: 12/30 (40%)
Deaths: 30/32
Cohort E: Glioblastoma Multiforma (Lenva + Pembro)
Serious: 30/101 (30%)
Deaths: 99/102
Cohort F: Biliary Tract Cancer (Lenva + Pembro)
Serious: 62/102 (61%)
Deaths: 98/103
Cohort G: Pancreatic Cancer (Lenva + Pembro)
Serious: 49/103 (48%)
Deaths: 101/103

Serious adverse events (223 terms)

ReactionSystemCohort A: Triple Negative …Cohort B: Ovarian Cancer (…Cohort C: Gastric Cancer (…Cohort D1: Colorectal Canc…Cohort D2: Colorectal Canc…Cohort E: Glioblastoma Mul…Cohort F: Biliary Tract Ca…Cohort G: Pancreatic Cance…
PyrexiaGeneral disorders
Abdominal painGastrointestinal disorders
CholangitisHepatobiliary disorders
Biliary obstructionHepatobiliary disorders
Biliary tract infectionInfections and infestations
Acute kidney injuryRenal and urinary disorders
DiarrhoeaGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
Urinary tract infectionInfections and infestations
Cardiac arrestCardiac disorders
HypophysitisEndocrine disorders
Abdominal pain upperGastrointestinal disorders
AscitesGastrointestinal disorders
ColitisGastrointestinal disorders
HaematemesisGastrointestinal disorders
Intestinal perforationGastrointestinal disorders
Large intestinal obstructionGastrointestinal disorders
NauseaGastrointestinal disorders
Oesophageal perforationGastrointestinal disorders
Rectal haemorrhageGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
Upper gastrointestinal haemorrhageGastrointestinal disorders
VomitingGastrointestinal disorders
FatigueGeneral disorders
Biliary tract disorderHepatobiliary disorders
Other adverse events (107 terms — click to expand)

ReactionSystemCohort A: Triple Negative …Cohort B: Ovarian Cancer (…Cohort C: Gastric Cancer (…Cohort D1: Colorectal Canc…Cohort D2: Colorectal Canc…Cohort E: Glioblastoma Mul…Cohort F: Biliary Tract Ca…Cohort G: Pancreatic Cance…
HypertensionVascular disorders
DiarrhoeaGastrointestinal disorders
HypothyroidismEndocrine disorders
Decreased appetiteMetabolism and nutrition disorders
FatigueGeneral disorders
ProteinuriaRenal and urinary disorders
NauseaGastrointestinal disorders
Abdominal painGastrointestinal disorders
DysphoniaRespiratory, thoracic and mediastinal disorders
AstheniaGeneral disorders
VomitingGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
HeadacheNervous system disorders
ConstipationGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Weight decreasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
AnaemiaBlood and lymphatic system disorders
MyalgiaMusculoskeletal and connective tissue disorders
RashSkin and subcutaneous tissue disorders
Mucosal inflammationGeneral disorders
Blood bilirubin increasedInvestigations
PruritusSkin and subcutaneous tissue disorders
Blood alkaline phosphatase increasedInvestigations
DyspnoeaRespiratory, thoracic and mediastinal disorders
HypokalaemiaMetabolism and nutrition disorders
StomatitisGastrointestinal disorders
Blood creatinine increasedInvestigations
Lipase increasedInvestigations
Platelet count decreasedInvestigations
HyponatraemiaMetabolism and nutrition disorders
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders
Dry mouthGastrointestinal disorders
HypoalbuminaemiaMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
Abdominal pain upperGastrointestinal disorders

Most-reported serious reactions: Pyrexia, Abdominal pain, Cholangitis, Biliary obstruction, Biliary tract infection, Acute kidney injury, Diarrhoea, Intestinal obstruction.

Data from ClinicalTrials.gov NCT03797326 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions.
    Wen PY, Weller M, Lee EQ, Alexander BM, et al · · 2020 · cited 908× · PMID 32328653 · DOI 10.1093/neuonc/noaa106
  2. Recent advances in therapeutic strategies for triple-negative breast cancer.
    Li Y, Zhang H, Merkher Y, Chen L, et al · · 2022 · cited 643× · PMID 36038913 · DOI 10.1186/s13045-022-01341-0
  3. Immunotherapy in colorectal cancer: current achievements and future perspective.
    Fan A, Wang B, Wang X, Nie Y, et al · · 2021 · cited 321× · PMID 34671202 · DOI 10.7150/ijbs.64077
  4. Exploring immunotherapy in colorectal cancer.
    Weng J, Li S, Zhu Z, Liu Q, et al · · 2022 · cited 250× · PMID 35842707 · DOI 10.1186/s13045-022-01294-4
  5. Understanding the immunosuppressive microenvironment of glioma: mechanistic insights and clinical perspectives.
    Lin H, Liu C, Hu A, Zhang D, et al · · 2024 · cited 232× · PMID 38720342 · DOI 10.1186/s13045-024-01544-7
  6. PD-L1, TMB, MSI, and Other Predictors of Response to Immune Checkpoint Inhibitors in Biliary Tract Cancer.
    Rizzo A, Ricci AD, Brandi G. · · 2021 · cited 207× · PMID 33535621 · DOI 10.3390/cancers13030558
  7. Advances in immunotherapy for triple-negative breast cancer.
    Liu Y, Hu Y, Xue J, Li J, et al · · 2023 · cited 198× · PMID 37660039 · DOI 10.1186/s12943-023-01850-7
  8. Tumor Microenvironment in Ovarian Cancer: Function and Therapeutic Strategy.
    Yang Y, Yang Y, Yang J, Zhao X, et al · · 2020 · cited 168× · PMID 32850861 · DOI 10.3389/fcell.2020.00758

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03797326.

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