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MelanomaPhase 1/2NCT05091346

A Study of E7386 in Combination With Pembrolizumab in Previously Treated Participants With Selected Solid Tumors

A Phase 1/2 study testing E7386, Pembrolizumab and Lenvatinib in people with Melanoma and Carcinoma, Hepatocellular, run by Eisai Inc. at 32 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The Phase 1b part of this study is conducted to assess the safety and tolerability of E7386 in combination with pembrolizumab in participants with previously treated selected solid tumors, and to determine the recommended Phase 2 dose (RP2D) of E7386 in combination with pembrolizumab. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
E7386, Pembrolizumab and Lenvatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
89 participants
Where
32 sitesin 4 countries
Study dates
27 Oct 2021to 15 Oct 2024
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female, age >=18 years at the time of informed consent
  • Have a histologically or cytologically-documented, advanced (metastatic and/or unresectable) selected solid tumor for which prior standard systemic therapy has failed. Selected tumor types: melanoma (excluding uveal melanoma), CRC, HCC
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Must have disease progression on current or since the last anticancer treatment
  • At least one measurable lesion by computer tomography (CT) or magnetic imaging resonance (MRI) based on RECIST 1.1
  • Adequate organ function and serum mineral level per blood work as confirmed by the investigator
Show all 18Show fewer
  • Calcium (albumin-corrected) within normal range
  • Potassium within normal reference range
  • Magnesium less than or equal to (>=) 1.2 milligram per deciliter (mg/dL) or 0.5 millimoles per litre (mmol/L).
  • Melanoma cohort (Phase 2), participants must have:
  • Unresectable Stage III or Stage IV melanoma, not amenable to local therapy.
  • Received only 1 or, if BRAF mut +ve, 2 lines of therapies locally advanced or metastatic setting prior to study enrolment. Note: Adjuvant anti-PD-1/PD-L1 mAb/ BRAF inhibitor treatment will be counted as prior line of treatment if relapse occurred during active treatment or within 12 weeks of treatment discontinuation.
  • CRC cohort (Phase 2), participants must have received at least 2 prior systemic therapies in adjuvant and/or metastatic setting (not exceeding 4 lines of therapies in the metastatic setting, progressed on at least 1 prior regimen in the metastatic setting or could not tolerate standard treatment)
  • Participants with HCC cohort (Phase 2) must have:
  • Stage B (not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment) or stage C based on Barcelona Clinic Liver Cancer [BCLC] staging System and Child-Pugh class A only.
  • Have received only 1 prior line of systemic therapy in the locally advanced or metastatic setting, and must have progressed on treatment with an anti-PD-1/L1 monoclonal antibodies (mAb) administered either as monotherapy, or in combination
  • Must agree to take Vitamin D continuous supplementation as per local institutional guideline/ investigator's clinical discretion if their 25-hydroxyvitamin D levels are less than 10 nanogram per milliliter (ng/mL).
  • Triplet treatment cohorts only: Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP <=150/90 millimeter of mercury (mmHg) at Screening/Baseline and no change in antihypertensive medications within 1 week before starting treatment in this study.

Who cannot join

  • Have present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to study drug administration. The participant can receive diuretic drugs as needed per the treating physician. Consult with the sponsor if the participant has more than trivial/trace fluid accumulation.
  • Prior treatment with E7386 or prior therapy with 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 (example, CTLA-4, OX 40, CD137) that was discontinued due to a Grade 3 or higher immune-related (ir)AE
  • Participants with central nervous system (CNS) metastases are not eligible unless they are previously treated are radiologically stable, that is, without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), and are clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
  • Any active infection requiring systemic treatment
  • Have severe hypersensitivity to study drugs and/or any of its excipients
  • Have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
Show all 32Show fewer
  • Have an active autoimmune disease that has required systemic treatment in the past 2 years
  • Have a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
  • Any bone disease/conditions as follows:
  • Osteoporosis with T-score <-2.5 by DXA scan
  • Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
  • Symptomatic hypercalcemia requiring bisphosphonate therapy
  • History of any fracture within 6 months prior to starting study drug
  • History of symptomatic vertebral fragility fracture or any fragility fracture
  • Moderate or severe morphometric vertebral fracture at baseline.
  • Any condition requiring orthopedic intervention.
  • Bone metastases not being treated with a bisphosphonate or denosumab
  • Active viral hepatitis (B or C) as demonstrated by positive serology for participants with melanoma and CRC. Dual active hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infection at study entry for participants with HCC
  • Known to be human immunodeficiency virus (HIV) positive
  • Received blood/platelet transfusion or G-CSF within 4 weeks before study entry
  • For Melanoma only, participants with ocular melanoma are excluded. Note: Participants with mucosal melanoma will not exceed 20% of the enrolled participants in melanoma cohort in Phase 2.
  • For CRC only, participants are excluded if:
  • have a tumor that is microsatellite instability high (MSI H)/ DNA mismatch repair-deficient (dMMR) positive
  • For HCC only, participants are excluded if:
  • Clear invasion to bile duct
  • Have had esophageal or gastric variceal bleeding within the last 6 months. Participants in triplet treatment cohorts will be screened for esophageal or gastric varices unless such screening has been performed in the past 3 months before first dose of treatment. If varices are present, they should be treated according to institutional standards before starting study intervention; esophageal or gastric varices that require interventional treatment within 28 days prior to first dose of study drug are excluded
  • History of hepatic encephalopathy within 6 months prior to starting study drug unresponsive to therapy within 3 days. Participants on rifaximin or lactulose during screening to control their hepatic encephalopathy are not allowed
  • For participants in the triplet treatment cohorts only:
  • Proteinuria greater than (>) 1+ on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein >=1 gram per 24 hours (g/24 hours) will be ineligible
  • Bleeding or thrombotic disorders or use of anticoagulants requiring therapeutic INR monitoring (example, warfarin or similar agents). Treatment with low molecular weight heparin and factor X inhibitors is permitted
  • Clinically significant hemoptysis from any source or tumor bleeding within 3 weeks prior to the first dose of study drug
  • Pre-existing >=Grade 3 gastrointestinal or non-gastrointestinal fistula

Trial locations and contacts

32 sites in 4 countries.

32 sites in 4 countries

United States10 sites

  • Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Barbara Ann Karmanos Cancer Center

    Detroit, Michigan, 48201

  • Florida Cancer Specialists

    Fort Myers, Florida, 33916

  • University of California, Los Angeles

    Los Angeles, California, 90095

  • Tennessee Oncology PPLC

    Nashville, Tennessee, 37203

  • Rutgers cancer Institute of NJ

    New Brunswick, New Jersey, 08901

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

  • University of California, Irvine Health

    Orange, California, 92868

  • Providence Medical Center Institute Franz Clinic

    Portland, Oregon, 97213

  • SCRI Florida Cancer Specialists East

    West Palm Beach, Florida, 33401

Other trials in United States

Japan9 sites

  • Chiba University Hospital

    Chiba

  • National Cancer Center Hospital

    Chūōku

  • Kurume University Hospital

    Fukuoka

  • National Cancer Center Hospital East

    Kashiwa

  • Osaka Metropolitan University Hospital

    Osaka

  • Kindai University Hospital

    Ōsaka-sayama

  • Sapporo-Kosei General Hospital

    Sapporo

  • Shizuoka Cancer Center Hospital

    Shizouka

  • Toranomon Hospital

    Tokyo

Other trials in Japan

Spain9 sites

  • Hospital Universitario de Badajoz

    Badajoz

  • Hospital Clinic de Barcelona

    Barcelona

  • Hospital Universitari Vall d'Hebron

    Barcelona

  • Hospital Clínico San Carlos

    Madrid, Calle Profesor Martín Lagos

  • Hospital General Universitario Gregorio Maranon

    Madrid

  • Hospital Universitario de la Paz

    Madrid

  • Hospital Regional Universitario de Malaga

    Málaga, Avenida Carolos Haya S/n

  • Clínica Universidad de Navarra

    Pamplona, Navarre

  • Consorcio Hospital General Universitario de Valencia

    Valencia

Other trials in Spain

United Kingdom4 sites

  • Beatson West of Scotland Cancer Centre

    Glasgow

  • Imperial College London - Hammersmith Hospital

    London

  • Royal Free Hospital NHS Foundation Trust

    London

  • The Christie NHS Foundation Trust

    Manchester

Other trials in United Kingdom

About this study

Official title: An Open-Label, Multicenter, Phase 1b/2 Study of E7386 in Combination With Pembrolizumab in Previously Treated Subjects With Selected Solid Tumors

The Phase 1b part of this study is conducted to assess the safety and tolerability of E7386 in combination with pembrolizumab in participants with previously treated selected solid tumors, and to determine the recommended Phase 2 dose (RP2D) of E7386 in combination with pembrolizumab.

The Phase 2 part of this study is conducted to assess the objective response rate (ORR) of E7386 in combination with pembrolizumab (melanoma, colorectal cancer [CRC], hepatocellular carcinoma [HCC]) or of E7386 in combination with pembrolizumab plus lenvatinib (HCC) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

Being tested
E7386, Pembrolizumab, Lenvatinib
Keywords
metastatic or unresectable melanoma, metastatic or unresectable hepatocellular carcinoma, metastatic or unresectable colorectal cancer, Solid tumors, E7386
Medical subject headings
Melanoma, Carcinoma, Hepatocellular, Colorectal Neoplasms, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • E7386Drug

    E7386 tablet.

  • PembrolizumabDrug

    Also called KEYTRUDA®

    Pembrolizumab IV infusion.

  • LenvatinibDrug

    Also called E7080

    Lenvatinib capsule.

Study groups in NCT05091346
Study groupRoleWhat they receive
Phase 1b and 2: E7386 + PembrolizumabExperimentalParticipants will receive E7386 twice daily (BID) along with pembrolizumab 200 mg intravenous (IV) infusion once every 3 weeks (Q3W) in 21-day treatment cycle until RP2D is determined in Phase 1b. The recommended dose for Phase 2 part of the study will be based on Phase 1b result. Participants will continue to receive study treatment in Phase 2 part until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the study.
Receives: Drug: E7386; Drug: Pembrolizumab
Phase 2: E7386 + Pembrolizumab + LenvatinibExperimentalParticipants will be randomized to receive E7386 Dose 1 (Cohort 1) or Dose 2 (Cohort 2) tablet, BID, orally in combination with pembrolizumab 200 mg Q3W IV infusion plus lenvatinib 8 mg capsule, orally, once daily (QD) continuously in 21-days treatment cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or termination of the study. The dose of treatment depends on tolerability data of both Cohorts.
Receives: Drug: E7386; Drug: Pembrolizumab; Drug: Lenvatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1b Part: Number of Participants With Dose-limiting Toxicities (DLTs)

    DLT was graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 based on investigator assessment. DLT was defined as any of the hematological or non-hematological toxicities events that: - Failure to administer greater than or equal to (>=) 75 percentage (%) of the planned dosage of E7386 as a result of treatment-related toxicity; - Any treatment-related toxicity that causes the participant to discontinue treatment, even if the toxicity does not meet DLT criteria; - Prolonged delay (greater than [>] 2 weeks) in initiating Cycle 2 due to treatment-related toxicities; - Any Grade 5 event or any death not clearly due to the underlying disease or extraneous causes.

    Measured: Cycle 1 (Cycle length=21 days)

  2. Phase 1b Part: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

    A TEAE was defined as an adverse event (AE) that emerged during treatment, having been absent at pretreatment (Baseline) or reemerged during treatment, or up to 30 days following last dose of study drug, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment or up to 30 days following last dose of study drug, relative to the pretreatment state, when the AE was continuous.

    Measured: Up to 30 days after last dose of study drug (up to 12.73 months)

  3. Phase 1b Part: Number of Participants With Serious TEAEs

    An SAE was any untoward medical occurrence that at any dose: Resulted in death; Was life-threatening (i.e., the participant was at immediate risk of death from the AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death); Required inpatient hospitalization or prolongation of existing hospitalization; Resulted in persistent or significant disability/incapacity; Was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug). An SAE was also counted as a TEAE if it emerged up to 90 days after the participant's last dose of study drug, or up to 30 days following cessation of study drug if the participant initiated new anticancer therapy, whichever was earlier.

    Measured: Up to 90 days after last dose of study drug (up to 14.73 months)

  4. Phase 2 Part: Objective Response Rate (ORR)

    ORR was defined as the percentage of participants achieving a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: Disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal (i.e., decrease in short axis to less than [<] 10 millimeters [mm]). PR: At least a 30 percent (%) decrease in sum of the diameters (SOD) of target lesions, taking as reference the screening SOD. Additionally, progression of target lesions must not be present.

    Measured: Up to 20.40 months

Secondary outcomes (9)

  1. Phase 1b Part: Percentage of Participants With Best Overall Response (BOR)

    BOR was defined as CR, PR, stable disease (SD), progressive disease (PD), and not applicable (NA)/not evaluable (NE) as per RECIST version 1.1. CR: Disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal (i.e., decrease in short axis to <10 mm). PR: At least a 30% decrease in SOD of target lesions, taking as reference screening SOD. Additionally, progression of target lesions must not be present. SD: Neither sufficient shrinkage of target lesions to qualify for PR, nor sufficient increase to qualify for PD. PD: At least a 20% increase in the SOD of target lesions, taking as reference nadir SOD (or the screening, if screening is nadir value). In addition to relative increase of 20% in SOD, the SOD must also demonstrate an absolute increase of >=5 mm. NA: No target lesions were identified at Screening.

    Measured: Up to 11.73 months

  2. Phase 1b and Phase 2 Parts: Duration of Response (DOR)

    DOR was defined as the time from the first documentation of CR or PR to the first documentation of PD or death due to any cause (whichever occurs first), in participants with confirmed CR or PR per RECIST 1.1. CR: Disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal (i.e., decrease in short axis to <10 mm). PR: At least a 30% decrease in SOD of target lesions, taking as reference screening SOD. Additionally, progression of target lesions must not be present. SD: Neither sufficient shrinkage of target lesions to qualify for PR, nor sufficient increase to qualify for PD. PD: At least a 20% increase in the SOD of target lesions, taking as reference nadir SOD (or the screening, if screening is nadir value). In addition to relative increase of 20% in SOD, the SOD must also demonstrate an absolute increase of >=5 mm.

    Measured: Phase 1b Part: Up to 11.73 months; Phase 2 Part: Up to 20.40 months

  3. Phase 1b and Phase 2 Parts: Disease Control Rate (DCR)

    DCR was defined as the percentage of participants who had a best overall response of confirmed CR or PR, or SD (after >=5 weeks from the first dose) as per RECIST 1.1. CR: Disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal (i.e., decrease in short axis to <10 mm). PR: At least a 30% decrease in SOD of target lesions, taking as reference screening SOD. Additionally, progression of target lesions must not be present. SD: Neither sufficient shrinkage of target lesions to qualify for PR, nor sufficient increase to qualify for PD. PD: At least a 20% increase in the SOD of target lesions, taking as reference nadir SOD (or the screening, if screening is nadir value). In addition to relative increase of 20% in SOD, the SOD must also demonstrate an absolute increase of >=5 mm.

    Measured: Phase 1b Part: Up to 11.73 months; Phase 2 Part: Up to 20.40 months

  4. Phase 1b and Phase 2 Parts: Clinical Benefit Rate (CBR)

    CBR was defined as the percentage of participants who had a best overall response of confirmed CR or PR, or durable SD (duration of SD >=23 weeks) per RECIST 1.1. CR: Disappearance of all non-nodal target lesions and any pathological lymph nodes must have become normal (i.e., decrease in short axis to <10 mm). PR: At least a 30% decrease in SOD of target lesions, taking as reference screening SOD. Additionally, progression of target lesions must not be present. SD: Neither sufficient shrinkage of target lesions to qualify for PR, nor sufficient increase to qualify for PD.

    Measured: Phase 1b Part: Up to 11.73 months; Phase 2 Part: Up to 20.40 months

  5. Phase 2 Part: Number of Participants With TEAEs and Treatment-related TEAEs

    A TEAE was defined as an AE that emerged during treatment, having been absent at pretreatment (Baseline) or reemerged during treatment, or up to 30 days following last dose of study drug, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment or up to 30 days following last dose of study drug, relative to the pretreatment state, when the AE was continuous. Related TEAEs was defined as AE for which a causal relationship between the study drug and the AE was a reasonable possibility.

    Measured: Up to 30 days after last dose of study drug (up to 21.40 months)

  6. Phase 1b Part, Cmax: Maximum Observed Plasma Concentration for E7386 When Co-administered With Pembrolizumab

    Cmax was defined as the maximum plasma concentration for E7386 when co-administered with Pembrolizumab. PK parameters were derived by noncompartmental analysis.

    Measured: Cycle 1 Days 1 and 8: Pre-dose up to 12 hours post-dose (Cycle 1 length=21 days)

  7. Phase 1b Part, Tmax: Time to Reach the Maximum Plasma Concentration for E7386 When Co-administered With Pembrolizumab

    Tmax was defined as the time to reach maximum observed plasma concentration for E7386 when co-administered with Pembrolizumab. PK parameters were derived by noncompartmental analysis.

    Measured: Cycle 1 Days 1 and 8: Pre-dose up to 12 hours post-dose (Cycle 1 length=21 days)

  8. Phase 1b Part, AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration for E7386 When Co-administered With Pembrolizumab

    AUC(0-t) was defined as the area under the plasma concentration-time curve from 0 (pre-dose) to time of last quantifiable concentration for E7386 when co-administered with Pembrolizumab. PK parameters were derived by noncompartmental analysis.

    Measured: Cycle 1 Days 1 and 8: Pre-dose up to 12 hours post-dose (Cycle 1 length=21 days)

  9. Phase 1b Part, CLss/F: Apparent Clearance From Plasma at Steady State for E7386 When Co-administered With Pembrolizumab

    CLss/F for E7386 when co-administered with Pembrolizumab was reported. PK parameters were derived by noncompartmental analysis.

    Measured: Cycle 1 Day 8: Pre-dose up to 12 hours post-dose (Cycle 1 length=21 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Oct 2021
  2. Study start27 Oct 2021
  3. Primary completion15 Oct 2024
  4. Study completion15 Oct 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
89 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05091346
Sponsor's protocol ID
E7386-G000-201
Other IDs
2021-001568-10, MK-3475-C83, 2023-505425-14, 2023
Status last verified
Oct 2024
First submitted
14 Oct 2021
Last updated
24 Oct 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing E7386, Pembrolizumab and Lenvatinib in people with Melanoma and Carcinoma, Hepatocellular, run by Eisai Inc. at 32 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites in United States, Japan, Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1b Part: Number of Participants With Dose-limiting Toxicities (DLTs) (time frame: Cycle 1 (Cycle length=21 days)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05091346.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2025.

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