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

NCT05091346 | Completed Phase 1 Results FDA Drug

• 4 other identifiers: E7386-G000-2012021-001568-10MK-3475-C832023-505425-14
• Study Type: interventional
• Target: 89
• Locations: 4 countries
• Sites: 32

Brief 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. 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.

Conditions

Melanoma; Carcinoma, Hepatocellular; Colorectal Neoplasms

Keywords

metastatic or unresectable melanoma; metastatic or unresectable hepatocellular carcinoma; metastatic or unresectable colorectal cancer; Solid tumors; E7386

Outcome Measures

Primary Outcomes (4)

• 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.

  Cycle 1 (Cycle length=21 days)

• 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.

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

• 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.

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

• 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.

  Up to 20.40 months

Secondary Outcomes (9)

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

  Up to 11.73 months

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

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

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

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

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

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

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

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

Study Arms (2)

Phase 1b and 2: E7386 + Pembrolizumab

EXPERIMENTAL

Participants 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.

Drug: E7386; Drug: Pembrolizumab

Phase 2: E7386 + Pembrolizumab + Lenvatinib

EXPERIMENTAL

Participants 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.

Drug: E7386; Drug: Pembrolizumab; Drug: Lenvatinib

Interventions

E7386 DRUG

E7386 tablet.

Phase 1b and 2: E7386 + Pembrolizumab; Phase 2: E7386 + Pembrolizumab + Lenvatinib

Pembrolizumab DRUG

Pembrolizumab IV infusion.

Also known as: KEYTRUDA®

Phase 1b and 2: E7386 + Pembrolizumab; Phase 2: E7386 + Pembrolizumab + Lenvatinib

Lenvatinib DRUG

Lenvatinib capsule.

Also known as: E7080

Phase 2: E7386 + Pembrolizumab + Lenvatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Eisai Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (32)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

University of California, Irvine Health

Orange, California, 92868, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33916, United States

Location

SCRI Florida Cancer Specialists East

West Palm Beach, Florida, 33401, United States

Location

Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Barbara Ann Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Rutgers cancer Institute of NJ

New Brunswick, New Jersey, 08901, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Providence Medical Center Institute Franz Clinic

Portland, Oregon, 97213, United States

Location

Tennessee Oncology PPLC

Nashville, Tennessee, 37203, United States

Location

Chiba University Hospital

Chiba, Japan

Location

National Cancer Center Hospital

Chūōku, Japan

Location

Kurume University Hospital

Fukuoka, Japan

Location

National Cancer Center Hospital East

Kashiwa, Japan

Location

Osaka Metropolitan University Hospital

Osaka, Japan

Location

Kindai University Hospital

Ōsaka-sayama, Japan

Location

Sapporo-Kosei General Hospital

Sapporo, Japan

Location

Shizuoka Cancer Center Hospital

Shizouka, Japan

Location

Toranomon Hospital

Tokyo, Japan

Location

Hospital Regional Universitario de Malaga

Málaga, Avenida Carolos Haya S/n, Spain

Location

Hospital Clínico San Carlos

Madrid, Calle Profesor Martín Lagos, Spain

Location

Clínica Universidad de Navarra

Pamplona, Navarre, Spain

Location

Hospital Universitario de Badajoz

Badajoz, Spain

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, Spain

Location

Hospital Universitario de la Paz

Madrid, Spain

Location

Consorcio Hospital General Universitario de Valencia

Valencia, Spain

Location

Beatson West of Scotland Cancer Centre

Glasgow, United Kingdom

Location

Imperial College London - Hammersmith Hospital

London, United Kingdom

Location

Royal Free Hospital NHS Foundation Trust

London, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, United Kingdom

Location

MeSH Terms

Conditions

Melanoma; Carcinoma, Hepatocellular; Colorectal Neoplasms; Neoplasm Metastasis

Interventions

E-7386; pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Liver Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_medinfo@eisai.com

1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2021
• First Posted: October 25, 2021
• Study Start: October 27, 2021
• Primary Completion: October 15, 2024
• Study Completion: October 15, 2024
• Last Updated: October 24, 2025
• Results First Posted: October 24, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

JP (9); GB (4); US (10); ES (9)