Two doses of dalpiciclib plus letrozole for first-line HR-positive, HER2-negative advanced breast cancer

A Multicenter, Randomized, Double-cohort Study of Different Doses of Dalpicicl Combined With Letrozole in the First-line Treatment of HR-positive, HER2-negative Advanced Breast Cancer

This trial tests whether two different doses of dalpiciclib combined with letrozole work well as first treatment for people with HR-positive, HER2-negative advanced breast cancer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: The Affiliated Hospital of Qingdao University (other)
• Drugs / interventions: chemotherapy
• Locations: 2 sites (Dalian, Liaoning and 1 other locations)
• Trial ID: NCT07285382 on ClinicalTrials.gov

What this trial studies

This is a prospective, open-label, randomized, multicenter phase II trial planning to enroll 120 patients as first-line therapy for HR-positive, HER2-negative advanced breast cancer. Patients are randomized via a centralized IWRS system and stratified by presence of visceral metastasis and disease-free interval. Participants are assigned to one of two cohorts receiving dalpiciclib (125 mg or 150 mg) plus letrozole 2.5 mg, with tumor imaging evaluated by investigators using RECIST 1.1. Safety follow-up occurs 28 days after the last dose and survival follow-up continues until death or study termination.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18–75 with HR-positive, HER2-negative advanced or metastatic breast cancer who are eligible for first-line endocrine-based therapy and meet the study's menopausal or LHRH-agonist requirements.

Not a fit: Patients with HER2-positive or triple-negative disease, those who require immediate cytotoxic chemotherapy, those with major uncontrolled comorbidities, or individuals outside the specified age or menopausal-treatment criteria are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, the combination could delay disease progression and postpone the need for chemotherapy, improving disease control and quality of life.

How similar studies have performed: Other CDK4/6 inhibitors combined with aromatase inhibitors have improved progression-free survival in HR-positive, HER2-negative advanced breast cancer, and dalpiciclib is a similar agent being tested in this context.

Eligibility criteria

Inclusion Criteria:

* Female patients aged ≥18 years and ≤75 years, who are postmenopausal or premenopausal/perimenopausal, and meet one of the following conditions:

  1. Have undergone bilateral oophorectomy in the past, or be aged ≥60 years; or
  2. Aged \<60 years, in a natural postmenopausal state (defined as spontaneous cessation of regular menstruation for at least 12 consecutive months without other pathological or physiological causes), with E2 and FSH at postmenopausal levels; or
  3. Premenopausal or perimenopausal female patients can also be enrolled, but must be willing to receive LHRH agonist treatment during the study period
* Patients with breast cancer confirmed by pathological examination to be HR-positive and HER2-negative, with evidence of focal recurrence or metastasis, not suitable for surgical resection or radiotherapy with the goal of cure, and without clinical indications for chemotherapy.

  1. ER-positive and/or PR-positive is defined as: the proportion of tumor cells with positive staining among all tumor cells is ≥1% (reviewed and confirmed by the investigator at the participating trial center);
  2. HER2-negative is defined as: standard immunohistochemistry (IHC) test result is 0/1+; ISH test shows that the HER2/CEP17 ratio is less than 2.0 or the HER2 gene copy number is less than 4 (reviewed and confirmed by the investigator at the participating trial center)
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1
* Have not previously received any systemic antineoplastic treatment for focal recurrent or metastatic disease
* Have measurable lesions in line with RECIST 1.1 criteria or only bone metastatic lesions (including osteolytic lesions or mixed osteolytic/osteoblastic lesions)
* Have sufficient organ and bone marrow function
* Women of childbearing potential must be willing to use a medically approved highly effective contraceptive method during the study period and within 3 months after the last administration of the study drug
* All acute toxic effects of previous antineoplastic treatment have resolved to grade 0-1 (according to NCI-CTCAE Version 5.0) or to the level specified in the inclusion/exclusion criteria. Except for other toxicities such as alopecia that the investigator deems to pose no safety risk to the patient
* Have given informed consent and signed the informed consent form, and be willing and able to comply with the planned visits, study treatment plan, laboratory tests and other trial procedures

Exclusion Criteria:

* Previously diagnosed with HER2-positive breast cancer by pathological examination
* Inflammatory breast cancer
* Disease progression or recurrence at 12 months or within 12 months after completion of previous neoadjuvant or adjuvant endocrine drug treatment
* Patients judged by the investigator to be unsuitable for endocrine treatment. Including advanced patients with symptoms, disseminated to internal organs, and at risk of life-threatening complications in the short term (including those with uncontrollable large effusions \[pleural, pericardial, peritoneal\], lymphangitis of the lung, and patients with more than 50% liver involvement) Confirmed to have brain metastatic lesions by cranial CT or MRI examination
* Have previously received any CDK4/6 inhibitor drug treatment
* Underwent major surgery, chemotherapy, radiotherapy, any investigational drug or other anticancer treatment within 2 weeks before entering the study Diagnosed with any other malignant tumor within 3 years before entering the study, except for non-melanoma skin cancer, basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix that have undergone radical treatment Human Immunodeficiency Virus (HIV) infection or known to have Acquired Immunodeficiency Syndrome (AIDS), active hepatitis B (HBV DNA ≥1000 IU/ml), hepatitis C (positive hepatitis C antibody and HCV-RNA higher than the lower limit of detection of the analytical method), or co-infection with hepatitis B and hepatitis C
* Within 6 months before entering the study, the following occurred: myocardial infarction, severe/unstable angina pectoris, NYHA class 2 or higher cardiac insufficiency, persistent arrhythmia of grade ≥2 (according to NCI-CTCAE Version 5.0), atrial fibrillation of any grade, coronary/peripheral artery bypass surgery, symptomatic congestive heart failure, cerebrovascular accident (including transient ischemic attack or symptomatic pulmonary embolism)
* Complicated with severe infection within 4 weeks before the first administration (e.g., requiring intravenous infusion of antibiotics, antifungal or antiviral drugs according to clinical diagnosis and treatment norms), or unexplained fever \>38.5℃ during the screening period/before the first administration
* Inability to swallow, intestinal obstruction, or other factors that affect drug administration and absorption
* Known allergy to the study drug or any excipients
* Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation
* Known history of psychiatric drug abuse or drug addiction
* Patients currently participating in other studies
* Have other serious physical or mental diseases or laboratory test abnormalities that may increase the risk of participating in the study, interfere with the study results, and are deemed unsuitable for participating in this study by the investigator

Where this trial is running

Dalian, Liaoning and 1 other locations

• The Second Affiliated Hospital of Dalian Medical University — Dalian, Liaoning, China (RECRUITING)
• Qingdao University Affiliated Hospital — Qingdao, Shandong, China (RECRUITING)

Study contacts

• Study coordinator: haibo Wang

Conditions: HR Positive HER2 Negative Advanced Breast Cancer