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.

NCT07666555 | Recruiting Phase 2

• 1 other identifier: RISE
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• ORR

  max 6 months

• DOR

  max 6 months

• OS

  5 years

Study Arms (2)

Culmerciclib combined with fulvestrant

EXPERIMENTAL

Culmerciclib combined with fulvestrant

Drug: Culmerciclib; Drug: Fulvestrant

investigator's choice of CDK4/6 inhibitor combined with fulvestrant

ACTIVE COMPARATOR

investigator's choice of CDK4/6 inhibitor combined with fulvestrant

Drug: CDK4/6 inhibitor; Drug: Fulvestrant

Interventions

CDK4/6 inhibitor DRUG

investigator's choice of CDK4/6 inhibitor

investigator's choice of CDK4/6 inhibitor combined with fulvestrant

Culmerciclib DRUG

CDK2/4/6 inhibitor

Culmerciclib combined with fulvestrant

Fulvestrant DRUG

Fulvestrant

Culmerciclib combined with fulvestrant; investigator's choice of CDK4/6 inhibitor combined with fulvestrant

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) 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.

You may not qualify if:

• \) 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

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan Cancer Center

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Fulvestrant

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Central Study Contacts

Zhimin Shao Professor

CONTACT

08664175590; zhimingshao@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: June 14, 2026
• First Posted: June 24, 2026
• Study Start: June 6, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 30, 2029
• Last Updated: June 24, 2026

Record last verified: 2026-06

Locations

CN (1)