A Study of SIM0270 Combined With Everolimus vs. Treatment of Physician's Choice in Patients With ER+/HER2- Advanced Breast Cancer (SIMRISE)

A Randomized, Open-label, Phase III Study of SIM0270 Combined With Everolimus Versus Treatment of Physician's Choice in Patients With CDK4/6 Inhibitors Previously Treated , ER+/HER2- Locally Advanced or Metastatic Breast Cancer

This Phase III, randomized, open label, multicenter study will evaluate the efficacy and safety of SIM0270 combined with everolimus compared to physician's choice of treatment in subjects with ER+/HER2- locally advanced or metastatic breast cancer who have had previous treatment with CDK4/6 inhibitor.

Study Overview

• Status: Active, not recruiting
• Conditions: Locally Advanced or Metastatic Breast Cancer
• Intervention / Treatment: Drug: SIM0270; Drug: Everolimus (Afinitor®); Drug: Exemestane tablets; Drug: Fulvestrant injection

• Study Type: Interventional
• Enrollment (Actual): 482
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China
      • The First Affiliated Hispital of Bengbu Medical University
    • Hefei, Anhui, China
      • AnHui Provincial Cancer Hospital
    • Hefei, Anhui, China
      • The First Affiliated Hispital of Anhui Medical University
    • Maanshan, Anhui, China
      • Maanshan People's Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Beijing Cancer Hospital
    • Beijing, Beijing Municipality, China
      • The First Medical Center of PLA Ggeneral Hospital
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China
      • The Second Affiliated Hospital of Chongqing Medical University
  • Fujian
    • Fuzhou, Fujian, China
      • Fujian Cancer Hospital
    • Fuzhou, Fujian, China
      • Fujian Provincial Hospital
  • Gansu
    • Lanzhou, Gansu, China
      • Gansu Provincial Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-sen University Cancer Center
    • Guangzhou, Guangdong, China
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
    • Guangzhou, Guangdong, China
      • Guangdong Maternal and Child Health Hospital
    • Zhongshan, Guangdong, China
      • Zhongshan City People's Hospital
  • Guangxi
    • Nanning, Guangxi, China
      • Guangxi Medical University Cancer Hospital
  • Hebei
    • Qinhuangdao, Hebei, China
      • First Hospital of Qinhuangdao
    • Shijiazhuang, Hebei, China
      • The Fourth Hospital of Hebei Medical University
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Harbin Medical University Cancer Hospital
  • Henan
    • Anyang, Henan, China
      • Anyang Tumor Hospital
    • Luoyang, Henan, China
      • The First Affiliated Hospital of Henan University of Science & Technology
    • Zhengzhou, Henan, China
      • The First Affiliated Hospital of Zhengzhou University
    • Zhengzhou, Henan, China
      • The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China
      • Hubei Cancer Hospital
    • Wuhan, Hubei, China
      • Wuhan University Zhongnan Hospital
    • Xiangyang, Hubei, China
      • Xiangyang Central Hospital
  • Hunan
    • Changde, Hunan, China
      • The First People's Hospital of Changde City
    • Changsha, Hunan, China
      • Hunan Cancer Hospital
    • Changsha, Hunan, China
      • Xiangya Hospital of Central South University
    • Yongzhou, Hunan, China
      • The Central Hospital of Yongzhou
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Cancer Hospital
    • Nanjing, Jiangsu, China
      • The First Affiliated Hospital of Nanjing Medical University
    • Nanjing, Jiangsu, China
      • Nanjing Drum Tower Hospital
    • Xuzhou, Jiangsu, China
      • Xuzhou Central Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Jiangxi Cancer Hospital
  • Jilin
    • Changchun, Jilin, China
      • The First Hospital of Jilin University
    • Changchun, Jilin, China
      • Jilin cancer hospital
  • Liaoning
    • Dalian, Liaoning, China
      • The Second Hospital of Dalian Medical University
    • Jinzhou, Liaoning, China
      • The First Affiliated Hospital of Jinzhou Medical University
    • Shenyang, Liaoning, China
      • The First Hospital of China Medical University
    • Shenyang, Liaoning, China
      • Liaoning Cancer Hospital & Institute
  • Shaanxi
    • Xi'an, Shaanxi, China
      • First Affiliated Hospital of Xian Jiaotong University
  • Shan'Xi
    • Baoji, Shan'Xi, China
      • Baoji Central Hospital
  • Shandong
    • Binzhou, Shandong, China
      • Binzhou Medical University Hospital
    • Jinan, Shandong, China
      • Shandong First Medical University and Shandong Academy of Medical Sciences
    • Linyi, Shandong, China
      • Linyi Cancer Hospital
    • Linyi, Shandong, China
      • Linyi People'S Hostipal
    • Qingdao, Shandong, China
      • The Affiliated Hospital of Qingdao University
    • Weifang, Shandong, China
      • Weifang People's Hospital
    • Weihai, Shandong, China
      • Weihai Municipal Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai Municipality, China
      • Shanghai General Hospital
    • Shanghai, Shanghai Municipality, China
      • Renji Hospital, Shanghai Jiao Tong University School of Medicine
  • Sichuan
    • Chengdu, Sichuan, China
      • Sichuan Cancer Hospital
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China
      • Tianjin Medical University Cancer Institute & Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China
      • Zhejiang Provincial People's Hospital
    • Ningbo, Zhejiang, China
      • Ningbo Medical Center Lihuili Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Subjects with histologically or cytologically confirmed ER+/HER2- locally advanced or metastatic breast cancer
2. Subjects must have at least one RECIST 1.1 measurable disease and /or at least 1 lytic or mixed (lytic + sclerotic) bone lesion
3. For women who are post menopausal must meet criteria as defined in the protocol.For women who are premenopausal or perimenopausal and for men: treatment with approved LHRH agonist therapy for screening period and the duration of study treatment

4. Have disease that has demonstrated progression on or after prior treatment:

   1. subjects had received 1 to 2 endocrine therapies in the locally advanced or metastatic setting with disease recurrence/disease progression while being treated with adjuvant endocrine therapy for ≥ 24 months and/or endocrine therapy in the locally advanced or metastatic setting, and derived a clinical benefit from therapy
   2. subjects had received ≤ 1 chemotherapy in the locally advanced or metastatic setting.
5. Eastern Cooperative Oncology Group Performance Status 0-1
6. Adequate organ function

exclusion criteria:

1. Prior treatment with a oral selective estrogen receptor degrader (SERD) or other investigational-ER-directed therapy, or any PI3K-AKI-mTOR inhibitors
2. Treatment with any investigational therapy within 28 days prior to study treatment.Treatment with moderate/strong CYP3A inhibitors or P-gP inhibitor within 14 days prior to first dose or moderate/strong CYP3A inducer within 28 days prior to first dose
3. Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term
4. Active or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
5. Active cardiac disease or history of cardiac dysfunction, as defined in the protocol
6. Pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; SIM0270 to be taken orally as a capsule in combination with Everolimus.	Drug: SIM0270; Experimental; Drug: Everolimus (Afinitor®); Experimental and Active comparator
Active Comparator: Control group; Investigator's choice of therapy of either: Fulvestrant alone (a solution for injection), or Everolimus in combination with exemestane, both a tablet to be taken orally.	Drug: Everolimus (Afinitor®); Experimental and Active comparator; Drug: Exemestane tablets; Active Comparator; Drug: Fulvestrant injection; Active Comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival(PFS) , as assessed by blinded independent review committee(BIRC) according to RECIST1.1	PFS was defined as the time from the date of randomization to the first documented disease progression or death from any cause, whichever occurrs first.	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival(PFS) , as assessed by investigator according to RECIST1.1	PFS was defined as the time from the date of randomization to the first documented disease progression or death from any cause, whichever occurrs first.	2 year
Overall Survival (OS)	OS is the time from the date of randomization to death from any cause.	3 year
The incidence and severity of adverse events (AEs) and serious adverse events (SAEs)	Frequency and severity of Adverse Events or Serious Adverse Events as defined by CTCAE version 5.0	3 year
Blood concentrations	Blood concentrations of SIM0270 and everolimus	At five specified time points of the first 6 cycles (each cycle is 28 days)
Objective Response Rate (ORR) by investigator	The objective response rate is defined as the percentage of subjects with a complete response or partial response.	2 year
Objective Response Rate (DOR) by investigator	The DoR is defined as the time from the date of first complete or partial response until the date of documented progression or death from any cause.	2 year
ORR by BIRC	The objective response rate is defined as the percentage of subjects with a complete response or partial response.	2 year
DOR by BIRC	The DoR is defined as the time from the date of first complete or partial response until the date of documented progression or death from any cause.	2 year
Clinical benefit rate(CBR) by investigator	The clinical benefit rate is defined as the percentage of subjects with a complete response or partial response or stable disease for ≥24 weeks.	2 year
CBR by BIRC	The clinical benefit rate is defined as the percentage of subjects with a complete response or partial response or stable disease for ≥24 weeks.	2 year
Time To Progression (TTP) by investigator	TTP is defined as the time from randomization until the date of first documented progression.	2 year
Time To Progression (TTP) by BIRC	TTP is defined as the time from randomization until the date of first documented progression.	2 year
Change from baseline in EQ-5D-5L scores	Change from baseline in EQ-5D-5L scores	2 year
Change from baseline in FACT-B scores	Change from baseline in FACT-B scores	2 year

Collaborators and Investigators

• Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd.
• Collaborators: Nanjing Zaiming Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2024
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2028

Study Registration Dates

• First Submitted: November 5, 2024
• First Submitted That Met QC Criteria: November 6, 2024
• First Posted (Actual): November 8, 2024

Study Record Updates

• Last Update Posted (Actual): August 11, 2026
• Last Update Submitted That Met QC Criteria: August 9, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Organic Chemicals; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Macrolides; Lactones; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Sirolimus; Fulvestrant; Everolimus; exemestane
• Other Study ID Numbers: SIM0270-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No