Locally Advanced or Metastatic Breast CancerPhase 2/3NCT05744687
Phase II/III Study of SPH4336 Combined With Letrozole vs Placebo Combined With Letrozole in First-line Treatment of Breast Cancer
A Phase 2/3 study testing SPH4336 Tablets 400mg in people with Locally Advanced or Metastatic Breast Cancer, run by Shanghai Pharmaceuticals Holding Co., Ltd at 9 sites in China.
Trial summary
This study is designed to evaluate the safety and efficacy of SPH4336 combined with letrozole in first-line treatment of locally advanced or metastatic breast cancer Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- Locally Advanced or Metastatic Breast Cancer
- What is being tested?
- SPH4336 Tablets 400mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 374 participants
- Where
- 9 sitesChina
- Study dates
- 24 Apr 2023to 31 May 2026
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who voluntarily participate in the study, completely understand the study, and voluntarily sign the informed consent form (ICF).
- Female, ≥ 18 and ≤ 75 years of age at the time of signing the ICF.
- ECOG（Eastern Cooperative Oncology Group） performance status 0 or 1.
- Life expectancy ≥ 3 months.
- Patients with locally advanced or metastatic breast cancer who are unable to receive radical surgeries/other local therapies, with hormone receptor positive and human epidermal growth factor receptor 2 negative confirmed by tumor histopathology and molecular pathology.
- No previous systemetic therapy for locally advanced or metastatic diseases that cannot receive radical surgeries/other local therapies.
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- At least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors.
- Postmenopausal or premenopausal/perimenopausal female patients. Premenopausal or perimenopausal women should consent to receive goserelin therapy during the study.
- Laboratory test results before randomization meet the relevant requirements for organ function.
Who cannot join
- Prior treatment with any CDK4/6 （Cyclin dependent kinase）inhibitor.
- Inflammatory breast cancer.
- Patients unsuitable for endocrine therapy at the investigator's discretion.
- History of other malignancies within 5 years prior to the start of study treatment.
- Patients with known central nervous system metastases.
- Taking anti-tumor traditional Chinese medicines at the time of signing the ICF.
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- Having undergone a surgery within 28 days prior to the start of study treatment, and hasn't yet recovered from adverse reactions of the surgery.
- 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; QTcF≥ 470 ms; LVEF(Left Ventricular Ejection Fractions)≤ 50%.
- History of ischemic stroke or severe thromboembolic disease before the start of study treatment.
- Being receiving potent CYP3A4 inhibitors or inducers at the time of signing the ICF.
- 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.
- Patients who participated in a clinical trial and received other investigational drugs within 30 days before the start of study treatment.
- History of severe anaphylactic diseases, history of severe drug allergy, or known allergy to any ingredient of the investigational product.
- Presence of diseases or conditions that may impact drug administration or gastrointestinal absorption before the start of study treatment, in the opinion of the investigator, makes them an unsuitable candidate for the study.
- Uncontrolled infections within 2 weeks before the start of study treatment, in the opinion of the investigator, makes them an unsuitable candidate for the study.
- Pregnant or lactating women.
- Known history of substance abuse, excessive drinking, or illegal drug addiction; history of confirmed neurological or mental disorders.
- Presence of other diseases judged by the investigator that the risks of receiving the study treatment outweigh its benefits, or any other reason for which patients are ineligible for the study as assessed by the investigator and the sponsor.
Trial locations and contacts
9 sites in 1 country. Contact the study team or a site near you to ask about taking part.
9 sites in 1 country
China9 sites, 9 recruiting
- Recruiting
AnYang Tumor Hospital
Anyang, Henan, 455001
Jing Sun, 0086-0372-2233016, ayzlyy@163.com
- Recruiting
Peking University Cancer Hospital
Beijing, 100142
Huiping Li, 0086-010-88121122, huipingli2012@hotmail.com
- Recruiting
The Second Norman Bethune Hospital of Jilin Univer
Changchun, Jilin, 130022
Jingwei Xu, 0086-0431-81136334, 1312600916@qq.com
- Recruiting
Fujian Cancer Hospital
Fuzhou, Fujian, 350014
Jian Liu, 0086-0591-62752181, fjszlyyjgb@163.com
- Recruiting
Affiliated Cancer Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510060
Shusen Wang, 0086-020-87343811, wangshs@sysucc.org.cn
- Recruiting
The Affiliated Cancer Hospital of Guizhou Medical University
Guiyang, Guizhou, 550000
Zhihong Wang, 0086-0851-86501211, 1453260207@qq.com
- Recruiting
The First Affiliated Hospital of Henan University of Science and Technology
Luoyang, Henan, 450052
Xinshuai Wang, 0086-0379-64922216, Hkdyfyllb@163.com
- Recruiting
Pingxiang People's Hospital
Pingxiang, Jiangxi, 337099
An Xiao, 0086-0799-6882099
- Recruiting
General Hospital of Ningxia Medical University
Yinchuan, Ningxia, 750003
Xinlan Liu, 0086-0951-6743648, nydzyec@126.com
About this study
Official title: Randomized, Double-blind, Placebo-controlled, Phase II/III Study of SPH4336 Combined With Letrozole vs Placebo Combined With Letrozole in First-line Treatment of HR-positive, HER2-negative Locally Advanced or Metastatic Breast Cancer
This study is designed to evaluate the safety and efficacy of SPH4336 combined with letrozole in first-line treatment of locally advanced or metastatic breast cancer
- Being tested
- SPH4336 Tablets 400mg, SPH4336 Tablets Placebo
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SPH4336 Tablets 400mgDrug
SPH4336 Tablets ：Orally, 400mg once a day; 28 days/cycle
Letrozole tablets ：Orally, 2.5mg once a day; 28 days/cycle
SPH4336 Tablets PlaceboDrug
SPH4336 Tablets Placebo：Orally,28 days/cycle
Letrozole tablets ：Orally, 2.5mg once a day; 28 days/cycle
| Study group | Role | What they receive |
|---|---|---|
| SPH4336 Tablets 400mg | Experimental | SPH4336 Tablets； Letrozole tablets Receives: Drug: SPH4336 Tablets 400mg |
| SPH4336 Tablets Placebo | Placebo comparator | SPH4336 Placebo； Letrozole tablets Receives: Drug: SPH4336 Tablets Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
response rate (ORR)
tumor response will be evaluated according to the Response Evaluation Criteria Solid Tumors (RECIST) criteria version 1.1.
Measured: Approximately 3years
Progression-free survival (PFS)
from the start date of study treatment to the date of progression disease or death , whichever occurred first.
Measured: Approximately 3years
Secondary outcomes (6)
Cmax
PK (Pharmacokinetics) parameters
Measured: Approximately 3years
Tmax
PK (Pharmacokinetics) parameters
Measured: Approximately 3years
Disease control rate (DCR)
DCR was defined as the percentage of patients who have achieved complete response, partial response and stable disease.
Measured: 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.
Measured: Approximately 3years
Overall Survival (OS)
Determination of the overall survival times of all patients.
Measured: Approximately 8years
Incidence of Adverse event
Safety and tolerability
Measured: Approximately 3years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2023
- Study start24 Apr 2023
- Primary completion31 May 2026 (estimated)
- Study completion31 May 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced or Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Shanghai Pharmaceuticals Holding Co., LtdThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 374 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Pharmaceuticals Holding Co., Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05744687
- Sponsor's protocol ID
- SPH4336-301
- Status last verified
- Aug 2025
- First submitted
- 16 Feb 2023
- Last updated
- 17 Aug 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double-blind, Placebo-controlled, Phase II/III Study of SPH4336 Combined With Letrozole vs Placebo Combined With Letrozole in First-line Treatment of HR-positive, HER2-negative Locally Advanced or Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT05744687
- Acronym / sponsor ID
- SPH4336-301
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 374 participants (estimated)
- Lead sponsor
- Shanghai Pharmaceuticals Holding Co., LtdIndustry (pharma, biotech, devices)
- Study start
- 24 Apr 2023 (actual)
- Primary completion
- 31 May 2026 (estimated)
- Study completion
- 31 May 2026 (estimated)
- First posted
- 27 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to evaluate the safety and efficacy of SPH4336 combined with letrozole in first-line treatment of locally advanced or metastatic breast cancer
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SPH4336 Tablets 400mg | Experimental | Drug: SPH4336 Tablets 400mgSPH4336 Tablets； Letrozole tablets |
| SPH4336 Tablets Placebo | Placebo comparator | Drug: SPH4336 Tablets PlaceboSPH4336 Placebo； Letrozole tablets |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients who voluntarily participate in the study, completely understand the study, and voluntarily sign the informed consent form (ICF).
- Female, ≥ 18 and ≤ 75 years of age at the time of signing the ICF.
- ECOG（Eastern Cooperative Oncology Group） performance status 0 or 1.
- Life expectancy ≥ 3 months.
- Patients with locally advanced or metastatic breast cancer who are unable to receive radical surgeries/other local therapies, with hormone receptor positive and human epidermal growth factor receptor 2 negative confirmed by tumor histopathology and molecular pathology.
Key exclusion criteria (18 listed)
- Prior treatment with any CDK4/6 （Cyclin dependent kinase）inhibitor.
- Inflammatory breast cancer.
- Patients unsuitable for endocrine therapy at the investigator's discretion.
- History of other malignancies within 5 years prior to the start of study treatment.
- Patients with known central nervous system metastases.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SPH4336 Tablets 400mgSPH4336 Tablets ：Orally, 400mg once a day; 28 days/cycle Letrozole tablets ：Orally, 2.5mg once a day; 28 days/cycle | Drug | SPH4336 Tablets 400mg |
| SPH4336 Tablets PlaceboSPH4336 Tablets Placebo：Orally,28 days/cycle Letrozole tablets ：Orally, 2.5mg once a day; 28 days/cycle | Drug | SPH4336 Tablets Placebo |
Primary outcome
response rate (ORR)
Time frame: Approximately 3years
tumor response will be evaluated according to the Response Evaluation Criteria Solid Tumors (RECIST) criteria version 1.1.
Progression-free survival (PFS)
Time frame: Approximately 3years
from the start date of study treatment to the date of progression disease or death , whichever occurred first.
6 secondary outcomes
Cmax
Time frame: Approximately 3years
Tmax
Time frame: Approximately 3years
Disease control rate (DCR)
Time frame: Approximately 3years
Duration of remission (DOR)
Time frame: Approximately 3years
Overall Survival (OS)
Time frame: Approximately 8years
Incidence of Adverse event
Time frame: Approximately 3years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing SPH4336 Tablets 400mg in people with Locally Advanced or Metastatic Breast Cancer, run by Shanghai Pharmaceuticals Holding Co., Ltd at 9 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Shusen Wang (0086-020-87343811, wangshs@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
response rate (ORR) (time frame: Approximately 3years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2025.