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

NCT05293964 | Active Not Recruiting Phase 1

• 1 other identifier: SIM-1907-02-SERD-101
• Study Type: interventional
• Target: 214
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose

  Dose Escalation: Maximum Tolerated Dose (MTD) of SIM0270 When Administered as a Single Agent or in Combination with Palbociclib or Everolimus

  At the end of Cycle 1 (each cycle is 28 days)

• recommended phase 2 Dose

  Dose Escalation: recommended phase 2 Dose (RP2D) of SIM0270 When Administered as a Single Agent or in Combination with Palbociclib or Everolimus

  At the end of Cycle 1 (each cycle is 28 days)

• Dose-Limiting Toxicities

  Dose Escalation: Number of Participants with Dose-Limiting Toxicities When SIM0270 is Administered as a Single Agent or in Combination with Palbociclib or Everolimus

  At the end of Cycle 1 (each cycle is 28 days)

Secondary Outcomes (12)

• Adverse event

  From Baseline until 30 days after the last dose of study treatment

• Peak Plasma Concentration (Cmax) of SIM0270 as monotherapy or combination with palbociclib or everolimus

  At the end of Cycle 4 (each cycle is 28 days)

• Time of Peak Plasma Concentration (Tmax) of SIM0270 as monotherapy or combination with palbociclib or everolimus

  At the end of Cycle 4 (each cycle is 28 days)

• Area under the plasma concentration versus time curve (AUC) of SIM0270 as monotherapy or combination with palbociclib or everolimus

  At the end of Cycle 4 (each cycle is 28 days)

• clinical benefit rate

  through study completion, an average of 1 year

Study Arms (3)

SIM0270

EXPERIMENTAL

Phase Ia SIM0270 monotherapy dose escalation and expansion

Drug: SIM0270

SIM0270+palbociclib

EXPERIMENTAL

Phase Ib SIM0270 with palbociclib dose escalation and expansion

Drug: SIM0270; Drug: Palbociclib

SIM0270+everolimus

EXPERIMENTAL

Phase Ib SIM0270 with everolimus dose escalation and expansion

Drug: SIM0270; Drug: everolimus

Interventions

SIM0270 DRUG

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

Also known as: SCR6852

SIM0270; SIM0270+everolimus; SIM0270+palbociclib

Palbociclib DRUG

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

SIM0270+palbociclib

everolimus DRUG

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

SIM0270+everolimus

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• Documented medical history or ongoing gastrointestinal disease or other malabsorption that may affect the absorption of oral study drug.
• 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;
• 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).
• Major surgical surgery (except biopsy) or incomplete healing of the surgical incision 4 times before the first study drug treatment;
• Known other malignant tumors within 2 years before enrollment (except treated basal cell carcinoma, scaly cell carcinoma and/or radical carcinoma in situ);
• 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);
• 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;
• known to interfere with the test requirements of mental illness or drug abuse disease.
• History of human immunodeficiency virus HIV infection, or active bacterial or fungal infection requiring systemic treatment .
• presence of active syphilis infection.
• Subjects with known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection with abnormal liver function.
• History of clinically significant cardiovascular disease.
• History of serious allergic reactions to the study drugs or excipients used in the protocol.
• Women who are pregnant or lactating.
• Prior use of SERD oral medications.

Sponsors & Collaborators

• Jiangsu Simcere Pharmaceutical Co., Ltd.: lead
• Nanjing Zaiming Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib; Everolimus

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Jiong Wu, phD

  chief physician

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 7, 2022
• First Posted: March 24, 2022
• Study Start: May 18, 2022
• Primary Completion: December 31, 2024
• Study Completion: September 8, 2025
• Last Updated: November 29, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)