A Study of E7090 as Monotherapy and in Combination With Other Anticancer Agents in Participants With Estrogen Receptor Positive (ER+) and Human Epidermal Growth Receptor 2 Negative (HER2-) Recurrent/Metastatic Breast Cancer

Phase 1Active Not RecruitingNCT04572295

Eisai Co., Ltd.51 enrolled

Overview

The primary purpose of this study is to evaluate the tolerability and safety of E7090 as monotherapy and in combination with other anticancer agents in participants with ER+, HER2- recurrent/metastatic breast cancer and to determine the recommended dose (RD) of E7090 in combination with other anticancer agents for subsequent phase studies.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Breast Neoplasms

Interventions

E7090DRUG

E7090 oral tablet.

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: Common to Part 1, 2 and 3 1. Participants who provided written voluntary informed consent for participation in the study. 2. Female participants who are age \>=18 years at the time of informed consent. 3. Post-menopausal or pre/peri-menopausal participants who have been continuously on concurrently given a luteinizing hormone-releasing hormone (LHRH) agonist since before the start of study treatment and is planned to continue this treatment during the study. 4. Participants with histologically confirmed diagnosis of progressive/recurrent or metastatic, ER+, HER2 negative breast cancer. 5. Participants who received prior CDK4/6 inhibitor treatment. 6. Participants with Performance Status (PS) score of 0-1 established by Eastern Cooperative Oncology Group (ECOG). 7. Part 1 and Part 2: Participants with at least one accessible lesion for biopsy and who agree to undergo a biopsy of accessible lesion prior to study treatment (if archived tissues collected after CDK4/6 inhibitor treatment is not available) and on Day 1 of Cycle 3. (Part 3) participants must agree to undergo a biopsy at screening if no archival tissue is available (tissue collection must be after CDK4/6 inhibitor treatment and prior to study treatment). A biopsy on Day 1 of Cycle 3 is not mandatory. 8. Participants who agree to provide archival or fresh tumor tissue collected after CDK4/6 inhibitor treatment. 9. Part 2 only: Participants with positive protein expression of fibroblast growth factor receptor 1 (FGFR) and/or FGFR2, with which tumor was collected after CDK4/6 inhibitor treatment at the central laboratory. Exclusion criteria: 1. Participants with brain or subdural metastases, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (example. radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment. 2. (Part 1 and Part 2) Participant who have received 2 or more regimen of chemotherapy for the treatment of advanced or metastatic lesions. 3. (Part 3) Participant who have received 1 or more regimens of chemotherapy or antibody-drug conjugate therapy for the treatment of advanced or metastatic lesions. 4. Participant with inflammatory breast cancer. 5. Participant with bilateral breast cancer of different histologic types. Participants who have bilateral breast cancers that are both ER+ and HER2- may be enrolled in the study. 6. Participant who have history of active malignancy within the past 24 months prior to the first dose of study drugs. 7. Participants with clinically significant cardiovascular impairment. 8. Presence of a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors. 9. Concomitant active infection requiring systemic treatment. 10. Participants who test positive for human immunodeficiency virus (HIV antibody), or positive for hepatitis B surface (HBs antigen) or hepatitis C (HCV antibody and RNA). 11. Participants with following ocular disorders: 1. Current evidence of Grade 2 or higher corneal disorder. 2. Current evidence of active retinopathy (example. age-related macular degeneration, central serous chorioretinal disease, retinal tear) 12. Participants who received prior treatment with an FGFR inhibitor. 13. Females who are pregnant or breastfeeding. 14. Part 1 only: Participants with T-score less than (\<) -2.5 by dual-energy X-ray absorptiometry (DXA) scan. 15. Part 3 only: Participants who received 3 or more prior lines of endocrine therapy in advanced/metastatic setting.

Locations (11)

Eisai Trial Site 11

Nagoya, Aichi-ken, Japan

Eisai Trial Site 6

Kashiwa, Chiba, Japan

Eisai Trial Site 9

Matsuyama, Ehime, Japan

Eisai Trial Site 5

Yokohama, Kanagawa, Japan

Eisai Trial Site 4

Sendai, Miyagi, Japan

Eisai Trial Site 7

Chuo-ku, Osaka, Japan

Eisai Trial Site 10

Kitaadachi-gun, Saitama, Japan

Eisai Trial Site 3

Chuo-ku, Tokyo, Japan

Eisai Trial Site 1

Koto-ku, Tokyo, Japan

Eisai Trial Site 2

Shinagawa-ku, Tokyo, Japan

...and 1 more locations

Outcomes

Primary Outcomes

Part 1: Recommended Dose (RD) of E7090 in Combination With Other Anticancer Agents

Time frame: Up to Cycle 1 (each cycle length = 28 days)

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

DLTs will be assessed based on combination regimen-related adverse events (AEs) occurred during Cycle 1 of Part 1 and the severity of AEs will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Time frame: Up to Cycle 1 (each cycle length = 28 days)

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Safety assessments will consist of monitoring and recording all AEs and SAEs; regular measurement of vital signs and ECG; and regular monitoring of clinical laboratory parameters, body weight and bone density.

Time frame: Up to 30 days after last administration of study drug (approximately up to 66 months)

Secondary Outcomes

Cmax: Maximum Observed Plasma Concentration of E7090, its Metabolite (M2) and Exemestane

Time frame: For E7090 and its metabolite (M2)- Parts 1 and 2 Cycle 1 Day 1: 0-24 hours post-dose; For exemestane- Part 1 Cycle 1 Day 1: 0-24 hours post-dose (each cycle length = 28 days)

AUC: Area Under the Plasma Concentration-time Curve of E7090, its Metabolite (M2) and Exemestane

Time frame: For E7090 and its metabolite (M2)- Parts 1 and 2 Cycle 1 Day 1: 0-24 hours post-dose; For exemestane- Part 1 Cycle 1 Day 1: 0-24 hours post-dose (each cycle length = 28 days)

Part 1: Plasma Concentration of Fulvestrant

Time frame: Cycles 2 and 3 Day 1: pre-dose (each cycle length = 28 days)

Objective Response Rate (ORR)

The ORR will be assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. ORR is defined as a percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR). CR: disappearance of all lesions. PR: For PR, longest diameter will be used for non-lymph target lesions but short axis is measured for lymph lesions. PR: greater than or equal to (\>=) 30 percent (%) decrease in sum of diameters of target lesions taking as reference baseline, associated to non-progressive disease (non-PD) response for non-target (NT) lesions.