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

A Single-Arm, Prospective, Multicenter Phase II Study of Culmerciclib Plus Letrozole and Trastuzumab (TQB211)/Pertuzumab (TQB2440) as Neoadjuvant Therapy in Patients With HR-Positive/HER2-Positive Early or Locally Advanced Breast Cancer

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer; HR Positive, HER2 Positive Breast Cancer
• Intervention / Treatment: Drug: Culmerciclib; Drug: Letrozole; Drug: Trastuzumab (TQB211); Drug: Pertuzumab (TQB2440)

Detailed Description

HR-positive/HER2-positive breast cancer accounts for approximately 10% of all breast cancers and shows lower pathological complete response rates to neoadjuvant therapy compared with the HR-negative/HER2-positive subtype. Crosstalk between HER2 and ER signaling pathways contributes to resistance to endocrine and anti-HER2 therapy. Preclinical evidence suggests that CDK4/6 inhibitors synergize with anti-HER2 therapy and may restore tumor sensitivity to HER2 blockade.

Eligible patients receive:

• culmerciclib 180 mg orally once daily, in 28-day cycles, for 5 cycles;
• Letrozole 2.5 mg orally once daily, in 28-day cycles, for 5 cycles;
• Trastuzumab (TQB211) 8 mg/kg loading dose followed by 6 mg/kg intravenously every 3 weeks, for 6 doses;
• Pertuzumab (TQB2440) 840 mg loading dose followed by 420 mg intravenously every 3 weeks, for 6 doses.

Tumor response is assessed by imaging (ultrasound, mammography, and MRI) according to RECIST 1.1. After completion of 5 cycles of neoadjuvant treatment, patients undergo definitive breast cancer surgery, and postoperative pathology is evaluated for bpCR and RCB. Adverse events are assessed per CTCAE v5.0. Exploratory analyses will investigate correlations between biomarkers and treatment response.

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mingda Zhao; Phone Number: +86-18509866694; Email: zhaomingda2021@163.com

Study Locations

• China
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Liaoning Cancer Hospital & Institute
      • Contact: Jianyi Li, MD, PhD; Phone Number: +86-13390127607; Email: sjbreast@yeah.net

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

Drug: Culmerciclib; 180 mg orally once daily, in 28-day cycles, for a total of 5 cycles.; Drug: Letrozole; 2.5 mg orally once daily, in 28-day cycles, for a total of 5 cycles.; Drug: Trastuzumab (TQB211); 8 mg/kg intravenous loading dose, followed by 6 mg/kg intravenously every 3 weeks, for a total of 6 doses.; Drug: Pertuzumab (TQB2440); 840 mg intravenous loading dose, followed by 420 mg intravenously every 3 weeks, for a total of 6 doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Proportion of patients achieving complete response (CR) or partial response (PR) assessed by imaging according to RECIST 1.1.	At end of neoadjuvant treatment (approximately 5 months from treatment start)
Residual Cancer Burden (RCB)	Residual cancer burden index and class (RCB-0, I, II, III) assessed by postoperative pathology.	At time of surgery (approximately 5 months from treatment start)
Ki67 Change Rate	Change in Ki67 proliferation index from baseline (pre-treatment biopsy) to surgery.	From baseline to surgery (approximately 5 months)
Patient-Reported Outcomes (PRO)	Patient-reported quality of life and symptom measures collected during treatment.	From baseline through end of treatment (approximately 5 months)
Incidence and Severity of Adverse Events	Number and severity of adverse events graded according to CTCAE v5.0.	From first dose through 30 days after surgery (approximately 6 months)

Collaborators and Investigators

• Sponsor: Shengjing Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: August 26, 2026
• First Submitted That Met QC Criteria: August 26, 2026
• First Posted (Actual): August 31, 2026

Study Record Updates

• Last Update Posted (Actual): August 31, 2026
• Last Update Submitted That Met QC Criteria: August 26, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Neoadjuvant Therapy CDK4/6 Inhibitor Culmerciclib Letrozole Trastuzumab Pertuzumab Chemotherapy-free
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nitriles; Triazoles; Trastuzumab; Letrozole; pertuzumab
• Other Study ID Numbers: IIT2026052

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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