Clinical trial NCT04572295: 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
Official title: An Open-label Phase 1b Study of E7090 Monotherapy and in Combination With Other Anticancer Agents in Subjects With ER+, HER2- Recurrent/Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Breast Neoplasms
Keywords: E7090
Fulvestrant
Exemestane
Receptors, Fibroblast Growth Factor
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2020-10-01
Enrollment: 51
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Part 1: Recommended Dose (RD) of E7090 in Combination With Other Anticancer Agents
timeFrame: Up to Cycle 1 (each cycle length = 28 days)
measure: Part 1: Number of Participants With Dose-limiting Toxicities (DLTs)
timeFrame: Up to Cycle 1 (each cycle length = 28 days)
measure: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 30 days after last administration of study drug (approximately up to 66 months)
Secondary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration of E7090, its Metabolite (M2) and Exemestane
timeFrame: 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)
measure: AUC: Area Under the Plasma Concentration-time Curve of E7090, its Metabolite (M2) and Exemestane
timeFrame: 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)
measure: Part 1: Plasma Concentration of Fulvestrant
timeFrame: Cycles 2 and 3 Day 1: pre-dose (each cycle length = 28 days)
measure: Objective Response Rate (ORR)
timeFrame: Baseline up to 66 months
measure: Disease Control Rate (DCR)
timeFrame: Baseline up to 66 months
measure: Clinical Benefit Response (CBR)
timeFrame: Baseline up to 66 months
measure: Progression-free Survival (PFS)
timeFrame: Baseline up to 66 months
measure: Overall Survival (OS)
timeFrame: Baseline up to 66 months
measure: Time to Response (TTR)
timeFrame: Baseline up to 66 months
measure: Duration of Response (DOR)
timeFrame: Baseline up to 66 months
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Eisai Trial Site 11
state: Aichi
city: Kashiwa
country: Japan
facility: Eisai Trial Site 6
state: Chiba
city: Matsuyama
country: Japan
facility: Eisai Trial Site 9
state: Ehime
city: Yokohama
country: Japan
facility: Eisai Trial Site 5
state: Kanagawa
city: Sendai
country: Japan
facility: Eisai Trial Site 4
state: Miyagi
city: Chuo-ku
country: Japan
facility: Eisai Trial Site 7
state: Osaka
city: Kitaadachi-gun
country: Japan
facility: Eisai Trial Site 10
state: Saitama
city: Chuo-ku
country: Japan
facility: Eisai Trial Site 3
state: Tokyo
city: Koto-ku
country: Japan
facility: Eisai Trial Site 1
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Eisai Trial Site 2
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Eisai Trial Site 8
state: Tokyo
Study officials:
References: