Phase I Study to Evaluate SIM0270 Alone or in Combination in ER+, HER2- Locally Advanced or Metastatic Breast Cancer

NCT ID: NCT05293964

Last Updated: 2024-11-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

214 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-05-18

Study Completion Date

2025-09-08

Brief Summary

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This study is a multi-center, open-label, Phase 1 clinical study to evaluate the safety, pharmacokinetic (PK) and anti-tumor efficacy of SIM0270 and SIM0270 in combination with palbociclib or everolimus in subjects with estrogen receptor (ER) -positive, human epidermal growth factor receptor (HER-2) -negative locally advanced or metastatic breast cancer.

Detailed Description

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The study is comprised of two parts: Phase Ia and Phase Ib. Phase Ia includes dose-escalating stage and dose expansion stageof SIM0270 monotherapy to determine the MTD/ RP2D and the preliminary safety and efficacy of SIM0270; Phase Ib includes 2 arms, armA: dose escalation and dose expansion of SIM0270 in combination with palbociclib; armB: dose escalation and dose expansion of SIM0270 in combination with palbociclib everolimus; phase Ib is designed to determine the MTD/RP2D and the preliminary safety and efficacy of SIM0270 in combination with palbociclib or everolimus.

Conditions

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Breast Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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SIM0270

Phase Ia SIM0270 monotherapy dose escalation and expansion

Group Type EXPERIMENTAL

SIM0270

Intervention Type DRUG

SIM0270 is an oral, selective estrogen receptor degrader (SERD)

SIM0270+palbociclib

Phase Ib SIM0270 with palbociclib dose escalation and expansion

Group Type EXPERIMENTAL

SIM0270

Intervention Type DRUG

SIM0270 is an oral, selective estrogen receptor degrader (SERD)

Palbociclib

Intervention Type DRUG

palbociclib is a selective inhibitor of cyclin D-cyclin-dependent kinase (CDK) 4/6

SIM0270+everolimus

Phase Ib SIM0270 with everolimus dose escalation and expansion

Group Type EXPERIMENTAL

SIM0270

Intervention Type DRUG

SIM0270 is an oral, selective estrogen receptor degrader (SERD)

everolimus

Intervention Type DRUG

Everolimus is an inhibitor of mTOR (mammalian target of rapamycin)

Interventions

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SIM0270

SIM0270 is an oral, selective estrogen receptor degrader (SERD)

Intervention Type DRUG

Palbociclib

palbociclib is a selective inhibitor of cyclin D-cyclin-dependent kinase (CDK) 4/6

Intervention Type DRUG

everolimus

Everolimus is an inhibitor of mTOR (mammalian target of rapamycin)

Intervention Type DRUG

Other Intervention Names

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SCR6852

Eligibility Criteria

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Inclusion Criteria

1. voluntary participation in clinical trials and signature of informed consent.
2. age ≥ 18 years, male or female.
3. Histologically or cytologically confirmed metastatic/locally advanced ER-positive, HER-2 negative breast cancer subjects.
4. previous treatment meets the criteria of the protocol defined.
5. ECOG score of 0 or 1 .
6. at least one measurable lesion that meets RECISTv1.1 criteria. Osteolytic lesions can be included in the Ia dose-escalating .
7. expected survival ≥ 12 weeks.
8. Adequate organ and bone marrow function.
9. Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose.
10. Postmenopausal women; Premenopausal or perimenopausal female subjects met protocol requirements.

Exclusion Criteria

1. Documented medical history or ongoing gastrointestinal disease or other malabsorption that may affect the absorption of oral study drug.
2. Participated in other clinical trials of investigational drugs or investigational devices within 28 days before the first medication; or received chemotherapy, targeted therapy, immunotherapy and clinical trial medication and other anti-tumor treatment within 4 days or 5 half-lives of the first medication (whichever is shorter), or received radiotherapy, endocrine drugs or Chinese patent medicines with anti-tumor indications 2 weeks before the first medication;
3. The toxicity of previous anti-tumor treatment has not recovered to grade 0 or 1 (alopecia, chemotherapy-induced peripheral neurotoxicity ≤ grade 2 can be included).
4. Major surgical surgery (except biopsy) or incomplete healing of the surgical incision 4 times before the first study drug treatment;
5. Known other malignant tumors within 2 years before enrollment (except treated basal cell carcinoma, scaly cell carcinoma and/or radical carcinoma in situ);
6. Leptomeningeal metastasis confirmed by MRI or known cytology of CSF, or cranial Increased internal pressure or brain metastases with unstable central nervous symptoms (within 2 weeks prior to initial medication Treatment with any craniotropic, glucocorticokinin, or anticonvulsant);
7. Previous history of interstitial lung disease, drug-induced interstitial lung disease, symptomatic interstitial lung disease or any evidence of active pneumonia on chest CT scan 4 before the first study drug treatment;
8. known to interfere with the test requirements of mental illness or drug abuse disease.
9. History of human immunodeficiency virus HIV infection, or active bacterial or fungal infection requiring systemic treatment .
10. presence of active syphilis infection.
11. Subjects with known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with abnormal liver function.
12. History of clinically significant cardiovascular disease.
13. History of serious allergic reactions to the study drugs or excipients used in the protocol.
14. Women who are pregnant or lactating.
15. Prior use of SERD oral medications.
16. Subjects who use drugs or herbal supplements known to be moderate/strong inhibitors of CYP3A 2 Weeks before the first dose.Or Subjects who use drugs or herbal supplements known to be moderate/strong inducers of CYP3A 4 weeks before the first dose.
17. Other conditions that the investigator considers unsuitable for this study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Nanjing Zaiming Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role collaborator

Jiangsu Simcere Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jiong Wu, phD

Role: PRINCIPAL_INVESTIGATOR

chief physician

Locations

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Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Site Status

Countries

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China

Other Identifiers

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SIM-1907-02-SERD-101

Identifier Type: -

Identifier Source: org_study_id