A Phase II Clinical Study of the Efficacy and Safety of Culmerciclib Rechallenge in HR-positive, HER2-negative Breast Cancer Patients With Resistance to First-line Endocrine Therapy.

A Phase II Clinical Trial Evaluating the Efficacy and Safety of Culmerciclib Combined With Fulvestrant Compared to an Investigator-Selected CDK4/6 Inhibitor Combined With Fulvestrant in Patients With HR-Positive, HER2-Negative Breast Cancer Who Have Progressed After First-Line Endocrine Therapy

To evaluate the efficacy and safety of Culmerciclib combined with fulvestrant compared with investigator-selected CDK4/6 inhibitors combined with fulvestrant in patients with HR-positive/HER2-negative breast cancer who have progressed after first-line endocrine therapy

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Fulvestrant; Drug: Culmerciclib; Drug: CDK4/6 inhibitor

Detailed Description

The study was a Randomized, open-label, multicenter design. Patients with dvanced HR+/HER2- breast cancer who had failed previous adjuvant treatment with CDK4/6 inhibitors in combination with endocrine therapy were treated with fulvestrant and Culmerciclib

• Study Type: Interventional
• Enrollment (Estimated): 98
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhimin Shao Professor; Phone Number: 8880 08664175590; Email: zhimingshao@yahoo.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Fudan Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1) Female, ≥18 years old; ≤ 75years old 2)ECOG score 0-2; 3) Predicted survival ≥3 months;Patients with locally advanced and/or metastatic breast cancer confirmed by histopathology with positive ER expression and negative HER2 expression; 5) Enrolled subjects must meet one of the following criteria regarding prior endocrine therapy: i) Received CDK4/6 inhibitor combined with endocrine therapy as adjuvant endocrine therapy, experienced recurrence or progression during or within 1 year after completion of adjuvant CDK4/6 inhibitor therapy, and did not receive subsequent endocrine therapy; ii) Recurrence or progression more than 1 year after completion of adjuvant endocrine monotherapy, followed by progression after receiving CDK4/6 inhibitor combined with endocrine therapy as first-line salvage endocrine therapy; iii) Newly diagnosed locally advanced or metastatic disease, with disease progression after receiving CDK4/6 inhibitor combined with endocrine therapy as first-line salvage endocrine therapy; 6)Participants with recurrent or metastatic disease may receive rescue chemotherapy, ADC, or rescue endocrine therapy not exceeding first-line treatment; 7) The time interval between non-endocrine therapy should be ≥2 weeks; 8) At least one extracranial measurable lesion as defined by RECIST V1.1 criteria; 9) The functions of vital organs meet the requirements; 10) Fertile subjects must have a negative pregnancy test 7 days before starting treatment and must use an appropriate contraceptive method during treatment and for three months after completion of treatment; 11) The patient is fully informed and voluntarily signs the informed consent.

Exclusion Criteria:

• 1) Previously diagnosed with HER2-positive breast cancer based on pathological testing; ; 2) Known allergy to the tested drug component; 3) inflammatory breast cancer at the time of screening; 4) pia meningeal metastasis confirmed by MRI or lumbar puncture; 5) Central nervous system metastasis confirmed by imaging; 6) To the best of the investigator's judgment, symptomatic visceral disease or any disease load or none is considered optimal Endocrine therapy options are not suitable for endocrine therapy; 7) Inability or unwillingness to swallow medication or receive intramuscular injections; 8) Gastrointestinal insufficiency or gastrointestinal disease (if not controlled) that may significantly affect study drug absorption Ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small intestine resection, etc.; 9) Patients with ascites, pleural effusion and pericardial effusion accompanied by clinical symptoms in the baseline period need drainage, or use it for the first time Patients with serous cavity drainage within 4 weeks before medication; 10) A history of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency conditions, Or have a history of organ transplantation; 11) Other malignancies (cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, and Thyroid cancer is excluded); 12) had undergone major surgical procedures or significant trauma within 4 weeks prior to the start of treatment, or was expected to undergo major surgery Surgical treatment; 13) Concomitant diseases that, in the investigator's judgment, seriously endanger patient safety or interfere with patient completion of the study (e.g.

Severe hypertension, diabetes, thyroid disease, co-active hepatitis B/C, and other activities Sexual infection); 14) Inability to understand or follow research instructions and requirements; 15) The researcher decides that it is not suitable to participate in this study

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: Culmerciclib combined with fulvestrant	Drug: Fulvestrant; Fulvestrant; Drug: Culmerciclib; CDK2/4/6 inhibitor
Active Comparator: investigator's choice of CDK4/6 inhibitor combined with fulvestrant	Drug: Fulvestrant; Fulvestrant; Drug: CDK4/6 inhibitor; investigator's choice of CDK4/6 inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	time to progressive disease (according to RECIST1.1)	Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 1 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	The proportion of participants whose best outcome is complete remission or partial remission (according to RECIST1.1)	max 6 months
DOR	Duration of Overall Response.The date of the first assessed PR/CR (according to RECIST 1.1) to the date of the first assessed tumor progression (according to RECIST 1.1) or death from any cause.	max 6 months
OS	ime from randomization (or start of treatment) to death from any cause	5 years

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): June 6, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 30, 2029

Study Registration Dates

• First Submitted: June 14, 2026
• First Submitted That Met QC Criteria: June 22, 2026
• First Posted (Actual): June 24, 2026

Study Record Updates

• Last Update Posted (Actual): June 24, 2026
• Last Update Submitted That Met QC Criteria: June 22, 2026
• Last Verified: June 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; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Fulvestrant
• Other Study ID Numbers: RISE

Drug and device information, study documents

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