Culmerciclib Combined With Letrozole and Dual HER2 Blockade as Neoadjuvant Therapy for HR+/HER2+ Breast Cancer

NCT07795424 | Not Yet Recruiting Phase 2

• 1 other identifier: IIT2026052
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, prospective, multicenter, phase II clinical study evaluating the efficacy and safety of a chemotherapy-free neoadjuvant regimen in patients with HR-positive/HER2-positive (HR+/HER2+) early or locally advanced breast cancer. Approximately 33 treatment-naive patients with stage II-III (AJCC 8th edition) HR+/HER2+ breast cancer will receive 5 cycles of neoadjuvant treatment with culmerciclib (a CDK4/6 inhibitor) plus letrozole, trastuzumab (TQB211) and pertuzumab (TQB2440), followed by definitive breast surgery. The primary endpoint is breast pathological complete response rate (bpCR, ypT0/is ypN0). Secondary endpoints include objective response rate (ORR), residual cancer burden (RCB), Ki67 change rate, patient-reported outcomes, and safety assessed per CTCAE v5.0.

Conditions

Breast Cancer; HR Positive, HER2 Positive Breast Cancer

Keywords

Neoadjuvant Therapy CDK4/6 Inhibitor Culmerciclib Letrozole Trastuzumab Pertuzumab Chemotherapy-free

Outcome Measures

Primary Outcomes (1)

• Breast Pathological Complete Response Rate (bpCR)

  Proportion of patients achieving ypT0/is ypN0 (no invasive cancer in the breast and no involved axillary lymph nodes), assessed by postoperative pathology.

  At time of surgery, after completion of 5 cycles of neoadjuvant therapy (approximately 5 months from treatment start)

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  At end of neoadjuvant treatment (approximately 5 months from treatment start)

• Residual Cancer Burden (RCB)

  At time of surgery (approximately 5 months from treatment start)

• Ki67 Change Rate

  From baseline to surgery (approximately 5 months)

• Patient-Reported Outcomes (PRO)

  From baseline through end of treatment (approximately 5 months)

• Incidence and Severity of Adverse Events

  From first dose through 30 days after surgery (approximately 6 months)

Study Arms (1)

Culmerciclib + Letrozole + TQB211 + TQB2440

EXPERIMENTAL

Patients receive Culmerciclib plus letrozole, trastuzumab (TQB211) and pertuzumab (TQB2440) as neoadjuvant therapy for 5 cycles, followed by definitive breast cancer surgery.

Drug: Culmerciclib; Drug: Letrozole; Drug: Trastuzumab (TQB211); Drug: Pertuzumab (TQB2440)

Interventions

Culmerciclib DRUG

180 mg orally once daily, in 28-day cycles, for a total of 5 cycles.

Culmerciclib + Letrozole + TQB211 + TQB2440

Letrozole DRUG

2.5 mg orally once daily, in 28-day cycles, for a total of 5 cycles.

Culmerciclib + Letrozole + TQB211 + TQB2440

Trastuzumab (TQB211) DRUG

8 mg/kg intravenous loading dose, followed by 6 mg/kg intravenously every 3 weeks, for a total of 6 doses.

Culmerciclib + Letrozole + TQB211 + TQB2440

Pertuzumab (TQB2440) DRUG

840 mg intravenous loading dose, followed by 420 mg intravenously every 3 weeks, for a total of 6 doses

Culmerciclib + Letrozole + TQB211 + TQB2440

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed HR-positive (ER \>=50%, PR \>=10%) and HER2-positive (IHC 3+ or ISH+) breast cancer;
• Clinical stage II-III (AJCC 8th edition);
• Treatment-naive: no prior systemic anti-tumor therapy for breast cancer;
• ECOG performance status 0-1;
• Adequate organ function;
• Signed informed consent.

You may not qualify if:

• Distant metastasis (stage IV disease);
• Prior chemotherapy, endocrine therapy, or anti-HER2 therapy for the current breast cancer;
• Severe cardiac dysfunction or left ventricular ejection fraction (LVEF) below the institutional lower limit of normal;
• Pregnancy or lactation;
• Any other condition that, in the investigator's opinion, makes the patient unsuitable for the study.

Sponsors & Collaborators

• Shengjing Hospital: lead

Study Sites (1)

Liaoning Cancer Hospital & Institute

Shenyang, Liaoning, 110042, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole; Trastuzumab; pertuzumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Mingda Zhao

CONTACT

+86-18509866694; zhaomingda2021@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: August 26, 2026
• First Posted: August 31, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: August 31, 2026

Record last verified: 2026-08

Locations

CN (1)