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

Phase 1

Conditions: colorectal cancer, hepatocellular carcinoma, melanoma
MedDRA version: 20.0Level: PTClassification code: 10073071Term: Hepatocellular carcinoma Class: 100000004864
MedDRA version: 21.0Level: PTClassification code: 10061451Term: Colorectal cancer Class: 100000004864
MedDRA version: 21.1Level: LLTClassification code: 10053571Term: Melanoma Class: 10029104
Therapeutic area: Diseases [C] - Neoplasms [C04]

Registration Number: CTIS2023-505425-14-00

Lead Sponsor: Eisai Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 105

Inclusion Criteria

Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol., ECOG PS of 0 to 1., Subject must have disease progression on current or since the last anticancer treatment., At least one measurable lesion by CT or MRI based on RECIST 1.1 confirmed by the investigator: a. At least 1 lesion of =1.0 cm in the longest diameter for a non-lymph node or =1.5 cm in the short-axis diameter for a lymph node that is serially measurable according to RECIST 1.1 using CT/MRI. b. Lesions that have had external beam radiotherapy or loco-regional therapies such as radiofrequency ablation, or transarterial chemoembolization (TACE)/transarterial embolization (TAE) must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion., Agree to consent for archival tumor tissue or a newly obtained biopsy tissue must be acquired prior to the first dose of study drug for biomarker analysis. Formalin-fixed paraffin embedded tissue block is preferred to slide. Newly obtained biopsy samples are preferred to archival tissue. In the case archival tissue cannot be provided, subjects with inaccessible tumors for biopsy specimens can be enrolled without a biopsy upon consultation and agreement by the Sponsor. For subjects with melanoma, in addition to pretreatment biopsy, C2D1 biopsy will be collected from the pre-designated non-target lesion, if they have recovered adequately from the biopsy taken prior to starting therapy). Note: If subject has only measurable lesion and no accessible non measurable disease, the subject can be enrolled without a biopsy upon consultation and agreement by the Sponsor). Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from when the slides are cut (details pertaining to the tumor tissue submission can be found in the Laboratory Manual)., Adequate renal function defined as creatinine clearance =30 mL/min per the Cockcroft and Gault formula (creatinine clearance =40 mL/min for subjects with HCC only), Adequate bone marrow function: a. ANC =1.5 × 109/L b. Platelets =100 × 109/L (platelets =75 × 109/L for subjects with HCC only). c. Hemoglobin =9.0 g/dL (criterion must be met without packed red blood cell [pRBC] transfusion within the prior 2 weeks). Subjects can be on stable dose of erythropoietin (approximately =3 months)., Adequate liver function: a. Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) =1.5 (=2.3 for subjects with HCC only) b. TBL =1.5 × ULN (=2.0 × ULN for subjects with HCC only) c. Alkaline phosphatase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) =3 × ULN (=5 × ULN for subjects with HCC only or if subject has liver metastasis)., All AEs due to previous anticancer therapy must have returned to Grade 0–1 except for alopecia and Grade 2 peripheral neuropathy., Subjects 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 ng/mL., Adequate serum mineral level: a. Calcium (albumin-corrected) within normal range b. Potassium within normal reference range c. Magnesium =1.2 mg/dL or 0.5 mmol/L., Male or female, age =18 years (or any age =18 years as determined by country legislation) at the time of informed consent., Life expectancy of =12 weeks., Have a histologically or cytolo

Exclusion Criteria

History of other active malignancy (except for original disease, or definitively treated basal or squamous cell skin carcinoma, carcinoma in-situ of the bladder or cervix) within the past 24 months prior to the first dose of study drug., Diagnosed meningeal carcinomatosis, Has severe hypersensitivity (Grade =3) to study drugs and/or any of its excipients including previous clinically-significant hypersensitivity reaction to treatment with another mAB., Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed., Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis., Active infection requiring systemic treatment., Active viral hepatitis (B or C) as demonstrated by positive serology for subjects with melanoma and CRC. For subjects with HCC: - Has dual active HBV infection (HBsAg [+] and /or detectable HBV DNA) and HCV infection (anti-HCV Ab [+] and detectable HCV RNA) at study entry., Known to be human immunodeficiency virus (HIV) positive. (Note: the Sponsor has evaluated whether to include subject with HIV. Given that this is the first combination study of E7386 with pembrolizumab and that the main mechanism of action of E7386 is immunomodulation of the tumor microenvironment along with the fact that several antiretroviral therapies have drug-drug interaction with cytochrome P450 3A4 (CYP3A) substrates, the Sponsor has decided not to include these subjects at the current time. However, further considerations will be made moving forward based on new emerging data)., Evidence of current COVID-19 infection or ongoing unrecovered sequelae of COVID-19 infection., Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator., Has a known psychiatric or substance abuse disorder that would interfere with the subject’s ability to cooperate with the requirements of the study., Major surgery within 21 days prior to starting study drug or minor surgery (ie, simple excision) within 1 week (subject must also have recovered from any surgery-related toxicities to less than CTCAE Grade 2). Note for triplet treatment cohorts: Adequate wound healing after major surgery must be assessed clinically., Evidence of clinically significant disease (eg, cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator(s) could affect the subject’s safety or interfere with the study assessments., Scheduled for major surgery during the study., Any of the bone disease/conditions as follows: a. see protocol b. Metabolic bone disease, such as hyperparathyroidism, Paget’s disease or osteomalacia. c. Symptomatic hypercalcemia requiring bisphosphonate therapy. d. History of any fracture within 6 months prior to starting study drug. e. History of symptomatic vertebral fragility fracture or any fragility fracture of the hip, pelvis, wrist or other location (defined as any fracture without a history of trauma or because of a fall from standi

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

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