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

NCT04572295 | Active Not Recruiting Phase 1

• 1 other identifier: E7090-J081-102
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 11

Brief Summary

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.

Conditions

Breast Neoplasms

Keywords

E7090; Fulvestrant; Exemestane; Receptors, Fibroblast Growth Factor

Outcome Measures

Primary Outcomes (3)

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

  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.

  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.

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

Secondary Outcomes (10)

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

  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

  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

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

• Objective Response Rate (ORR)

  Baseline up to 66 months

• Disease Control Rate (DCR)

  Baseline up to 66 months

Study Arms (3)

Part 1 Dose Escalation: E7090 + Fulvestrant or Exemestane

EXPERIMENTAL

Participants will receive E7090 tablets, orally, once daily along with fulvestrant 500 milligram (mg), intramuscular injection on Days 1 and 15 of Cycle 1 and each Day 1 of cycle 2 or later, or along with exemestane 25 mg tablet, orally, once daily in 28 days cycle. Each cycle length equals to (=) 28 days.

Drug: E7090; Drug: Fulvestrant; Drug: Exemestane

Part 2 Monotherapy: E7090

EXPERIMENTAL

Participants will receive E7090 tablets, orally, once daily in 28 days cycle. Each cycle length =28 days.

Drug: E7090

Part 3 Dose Expansion: E7090 + Fulvestrant

EXPERIMENTAL

Participants will receive E7090 tablets, orally, once daily along with fulvestrant 500 mg, intramuscular injection on Days 1 and 15 of Cycle 1 and each Day 1 of cycle 2 or later. Each cycle length =28 days. The dose of E7090 for Part 3 in combination with fulvestrant will be determined based on the safety, tolerability, pharmacokinetic (PK), and biomarker data obtained from Part 1.

Drug: E7090; Drug: Fulvestrant

Interventions

E7090 DRUG

E7090 oral tablet.

Part 1 Dose Escalation: E7090 + Fulvestrant or Exemestane; Part 2 Monotherapy: E7090; Part 3 Dose Expansion: E7090 + Fulvestrant

Fulvestrant DRUG

Fulvestrant intramuscular injection.

Part 1 Dose Escalation: E7090 + Fulvestrant or Exemestane; Part 3 Dose Expansion: E7090 + Fulvestrant

Exemestane DRUG

Exemestane oral tablet.

Part 1 Dose Escalation: E7090 + Fulvestrant or Exemestane

Eligibility Criteria

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

You may qualify if:

• Common to Part 1, 2 and 3
• Participants who provided written voluntary informed consent for participation in the study.
• Female participants who are age \>=18 years at the time of informed consent.
• 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.
• Participants with histologically confirmed diagnosis of progressive/recurrent or metastatic, ER+, HER2 negative breast cancer.
• Participants who received prior CDK4/6 inhibitor treatment.
• Participants with Performance Status (PS) score of 0-1 established by Eastern Cooperative Oncology Group (ECOG).
• 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.
• Participants who agree to provide archival or fresh tumor tissue collected after CDK4/6 inhibitor treatment.
• 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.

You may not qualify if:

• 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.
• (Part 1 and Part 2) Participant who have received 2 or more regimen of chemotherapy for the treatment of advanced or metastatic lesions.
• (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.
• Participant with inflammatory breast cancer.
• 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.
• Participant who have history of active malignancy within the past 24 months prior to the first dose of study drugs.
• Participants with clinically significant cardiovascular impairment.
• Presence of a progressive central nervous system (CNS) disease, including degenerative CNS diseases and progressive tumors.
• Concomitant active infection requiring systemic treatment.
• 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).
• Participants with following ocular disorders:
• Current evidence of Grade 2 or higher corneal disorder.
• Current evidence of active retinopathy (example. age-related macular degeneration, central serous chorioretinal disease, retinal tear)
• Participants who received prior treatment with an FGFR inhibitor.
• Females who are pregnant or breastfeeding.

Sponsors & Collaborators

• Eisai Co., Ltd.: lead

Study Sites (11)

Eisai Trial Site 11

Nagoya, Aichi-ken, Japan

Location

Eisai Trial Site 6

Kashiwa, Chiba, Japan

Location

Eisai Trial Site 9

Matsuyama, Ehime, Japan

Location

Eisai Trial Site 5

Yokohama, Kanagawa, Japan

Location

Eisai Trial Site 4

Sendai, Miyagi, Japan

Location

Eisai Trial Site 7

Chuo-ku, Osaka, Japan

Location

Eisai Trial Site 10

Kitaadachi-gun, Saitama, Japan

Location

Eisai Trial Site 3

Chuo-ku, Tokyo, Japan

Location

Eisai Trial Site 1

Koto-ku, Tokyo, Japan

Location

Eisai Trial Site 2

Shinagawa-ku, Tokyo, Japan

Location

Eisai Trial Site 8

Shinjuku-ku, Tokyo, Japan

Location

MeSH Terms

Conditions

Breast Neoplasms; Acrocephalosyndactylia

Interventions

Fulvestrant; exemestane

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Craniosynostoses; Synostosis; Dysostoses; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Syndactyly; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Limb Deformities, Congenital; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Design

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

Study Record Dates

• First Submitted: September 30, 2020
• First Posted: October 1, 2020
• Study Start: October 9, 2020
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

JP (11)