Safety and Efficacy of SPH4336 in Combination With Endocrine Therapy in the Treatment of Locally Advanced or Metastatic Breast Cancer

A Phase II/III Study of SPH4336 in Combination With Endocrine Therapy in the Treatment of HR-positive, HER2-negative Locally Advanced or Metastatic Breast Cancer That Progressed on CDK4/6 Inhibitor Combined With Endocrine Therapy

This study evaluated the safety and efficacy of SPH4336 in combination with endocrine therapy in the treatment of locally advanced or metastatic breast cancer that progressed on CDK4/6 inhibitor combined with endocrine therapy.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced or Metastatic Breast Cancer
• Intervention / Treatment: Drug: SPH4336 Tablets; Drug: SPH4336 Tablets Placebo

• Study Type: Interventional
• Enrollment (Estimated): 254
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Shusen Wang; Phone Number: 0086-020-87343811; Email: wangshs@sysucc.org.cn

Study Locations

• China
  • Beijing, China, 100730
    • Recruiting
    • Peking Union Medical College Hospital
    • Contact: Chunmei Bai
  • Bengbu, China
    • Recruiting
    • The First Affiliated Hospital of Bengbu Medical College
    • Contact: Jun Qian
  • Fuzhou, China
    • Recruiting
    • Fujian Cancer Hospital
    • Contact: Weiwei Huang
  • Kunming, China
    • Recruiting
    • First Affiliated Hospital of Kunming Medical University
    • Contact: Jinxian Qian
  • Shenzhen, China
    • Recruiting
    • Shenzhen Hospital of University of Hong Kong
    • Contact: Haiman Jing
  • Tianjin, China
    • Recruiting
    • Tianjin Medical University Cancer Institute & Hospital
    • Contact: Yehui Shi
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Affiliated Cancer Hospital, Sun Yat-sen University
      • Contact: Shusen Wang; Phone Number: 0086-020-87343811; Email: wangshs@sysucc.org.cn
  • Guangxi
    • Liuchow, Guangxi, China, 545026
      • Recruiting
      • Liuzhou People's Hospital
      • Contact: Bin Yu
  • He'nan
    • Anyang, He'nan, China, 455001
      • Recruiting
      • Anyang Cancer Hospital
      • Contact: Jing Sun
    • Luoyang, He'nan, China, 450052
      • Recruiting
      • The First Affiliated Hospital of Henan University of Science And Technology
      • Contact: Xinshuai Wang
  • Hebei
    • Shijiazhuang, Hebei, China, 050011
      • Recruiting
      • The Fourth Hospital of Hebei Medical University
      • Contact: Cuizhi Geng
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Recruiting
      • Harbin Medical University Cancer Hospital
      • Contact: Qingyuan Zhang
  • Hubei
    • Wuhan, Hubei, China, 441021
      • Recruiting
      • Xiangyang Cancer Hospital
      • Contact: Yuehua Wang
  • Jiangsu
    • Nanjing, Jiangsu, China, 210009
      • Recruiting
      • Jiangsu Cancer Hospital
      • Contact: Jifeng Feng
    • Nanjing, Jiangsu, China, 210029
      • Recruiting
      • Jiangsu Province Hospital
      • Contact: Yongmei Yin
  • Jilin
    • Changchun, Jilin, China, 130012
      • Recruiting
      • Jilin Cancer Hospital
      • Contact: Ying Cheng
  • Liaoning
    • Shenyang, Liaoning, China, 110002
      • Recruiting
      • The First Hospital of China Medical University
      • Contact: Yue'e Teng
  • Ningxia
    • Yinchuan, Ningxia, China, 750003
      • Recruiting
      • General Hospital of Ningxia Medical University
      • Contact: Xinlan Liu
  • Shanxi
    • Xi’an, Shanxi, China, 710061
      • Recruiting
      • The First Affiliated Hospital of Xi'an Jiao Tong University
      • Contact: Jin Yang
  • Sichuan
    • Neijiang, Sichuan, China, 641199
      • Recruiting
      • The Second People's Hospital of Neijiang
      • Contact: Xujuan Wang
  • Yunnan
    • Kunming, Yunnan, China, 650118
      • Recruiting
      • Yunnan Cancer Hospital
      • Contact: Jianyun Nie
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310005
      • Recruiting
      • Zhejiang Cancer Hospital
      • Contact: Zhanhong Chen

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients who voluntarily participate in this study, completely understand this study, and voluntarily sign the informed consent form (ICF).
2. ECOG (Eastern Cooperative Oncology Group) performance status score of 0 or 1.
3. Life expectancy ≥ 3 months.
4. Patients with locally advanced or metastatic breast cancer who are unable to receive radical surgeries/other local therapies.
5. At least one measurable lesion.
6. Laboratory test results meet the relevant requirements for organ function.
7. Subjects who agree to take effective contraceptive measures.

Exclusion Criteria:

1. Inflammatory breast cancer.
2. Patients unsuitable for endocrine therapy at the investigator's discretion.
3. History of other malignancies prior to the start of study treatment.
4. Patients with known metastases to central nervous system.
5. Taking anti-tumor traditional Chinese patent medicines at the time of signing the ICF.
6. Patients who underwent a surgery prior to the start of study treatment, and have not yet recovered from adverse reactions of the surgery.
7. Patients who participated in a clinical trial and received other investigational drugs before the start of study treatment.
8. Pregnant or lactating women.
9. History of myocardial infarction, unstable angina pectoris, severe arrhythmia, and symptomatic congestive heart failure before the start of study treatment; ≥ NYHA (New York Heart Association) Class II; mean QTc interval ≥ 470 ms before the start of study treatment; left ventricular ejection fraction ≤ 50% before the start of study treatment.
10. History of ischemic stroke or severe thromboembolic disease before the start of study treatment.
11. Hepatitis B surface antigen positive and HBV (Hepatitis B Virus) DNA > 2,000 IU/mL or > 104 copies/mL; HCV (Hepatitis C Virus) antibody positive and HCV RNA positive; or known HIV infection.
12. History of severe allergic diseases, history of severe drug allergies, or known allergy to any ingredient of the investigational product.
13. Presence of diseases or conditions that may impact drug administration or gastrointestinal absorption before the start of study treatment.
14. Presence of uncontrolled infections before the start of study treatment.
15. Known history of drug abuse, excessive drinking, or illegal drug use; history of confirmed neurological or mental disorders.
16. Presence of other diseases that the risks of receiving the study treatment outweigh its benefits, as determined by the investigator, or any other reason for which patients are ineligible for the study as assessed by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SPH4336 Tablets; SPH4336 Tablets; Letrozole tablets; Fulvestrant injection	Drug: SPH4336 Tablets; SPH4336 Tablets ：Administered by oral; Letrozole tablets：Administered by oral; Fulvestrant injection：Administered by intravenous infusion
Placebo Comparator: SPH4336 Tablets Placebo; SPH4336 Tablets Placebo; Letrozole tablets; Fulvestrant injection	Drug: SPH4336 Tablets Placebo; SPH4336 Tablets Placebo ：Administered by oral; Letrozole tablets：Administered by oral; Fulvestrant injection：Administered by intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	from the start date of study treatment to the date of progression disease or death , whichever occurred first.	Approximately 3years
Objective response rate	tumor response will be evaluated according to the Response Evaluation Criteria Solid Tumors (RECIST) criteria version 1.1.	Approximately 3years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	PK (Pharmacokinetics) parameters	Approximately 3years
Tmax	PK (Pharmacokinetics) parameters	Approximately 3years
Disease control rate (DCR)	DCR was defined as the percentage of patients who have achieved complete response, partial response and stable disease	Approximately 3years
Duration of remission (DOR)	DOR was defined for participants who had an objective response as the time from the first occurrence of a documented unconfirmed response to the date of disease progression per RECIST v1.1 or death from any cause	Approximately 3years
Overall Survival (OS)	Determination of the overall survival times of all patients	Approximately 8years
Safety and tolerability of the combination therapy since the start of any study treatment.	Adverse event type, incidence, duration, correlation with study drug	Approximately 3years

Collaborators and Investigators

• Sponsor: Shanghai Pharmaceuticals Holding Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: May 8, 2023
• First Submitted That Met QC Criteria: May 8, 2023
• First Posted (Actual): May 16, 2023

Study Record Updates

• Last Update Posted (Estimated): January 14, 2026
• Last Update Submitted That Met QC Criteria: January 12, 2026
• Last Verified: August 1, 2025

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
• Other Study ID Numbers: SPH4336-302

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No