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

Completed · Phase 1/Phase 2

Conditions studied: Melanoma, Carcinoma, Hepatocellular, Colorectal Neoplasms

In brief

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.

Key facts

Study ID

NCT05091346

Run by

Eisai Inc.

People needed

89

Starts

2021-10-27

Expected to finish

2024-10-15

Last updated by the study team

2025-10-24

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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.
• 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.

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.
• 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

Where it is running

• Hospital Clinic de Barcelona — Barcelona, Spain
• Hospital Universitari Vall d'Hebron — Barcelona, Spain
• University of California, Los Angeles — Los Angeles, California, United States
• University of California, Irvine Health — Orange, California, United States
• Florida Cancer Specialists — Fort Myers, Florida, United States
• SCRI Florida Cancer Specialists East — West Palm Beach, Florida, United States
• Winship Cancer Institute — Atlanta, Georgia, United States
• Barbara Ann Karmanos Cancer Center — Detroit, Michigan, United States
• Rutgers cancer Institute of NJ — New Brunswick, New Jersey, United States
• Icahn School of Medicine at Mount Sinai — New York, New York, United States
• Providence Medical Center Institute Franz Clinic — Portland, Oregon, United States
• Tennessee Oncology PPLC — Nashville, Tennessee, United States
• Chiba University Hospital — Chiba, Japan
• National Cancer Center Hospital — Chūōku, Japan
• Kurume University Hospital — Fukuoka, Japan
• National Cancer Center Hospital East — Kashiwa, Japan
• Osaka Metropolitan University Hospital — Osaka, Japan
• Kindai University Hospital — Ōsaka-sayama, Japan
• Sapporo-Kosei General Hospital — Sapporo, Japan
• Shizuoka Cancer Center Hospital — Shizouka, Japan
• Toranomon Hospital — Tokyo, Japan
• Hospital Regional Universitario de Malaga — Málaga, Avenida Carolos Haya S/n, Spain
• Hospital Clínico San Carlos — Madrid, Calle Profesor Martín Lagos, Spain
• Clínica Universidad de Navarra — Pamplona, Navarre, Spain
• Hospital Universitario de Badajoz — Badajoz, Spain

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.