Chemotherapy With or Without Adebrelimab and T-DXh as Neoadjuvant Therapy for HR+/HER2 Low Early Stage Breast Cancer

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Begins enrollment this month; Phase 2

Conditions: HR Positive/HER2 Low Breast Cancer; Breast Cancer Early Stage Breast Cancer (Stage 1-3)

Treatments: Drug: SHR-A1811; Drug: Anthracycline & Cyclophosphamide treatment scheme; Drug: Taxane Chemotherapy; Drug: Adebrelimab (PD-L1 inhibitor)

Study type: Interventional

Funder types: Other

Identifiers

NCT07317778

MA-BC-II-094

Details and patient eligibility

About

The goal of this clinical trial is to learn if add SHR-A1811 and/or Adebrelimab on standard chemotherapy could further improve the pCR rate in HR+/HER2 low early stage breast cancer patients. It will also learn about the safety of these combination regimen. The main questions it aims to answer are:

Is Adebrelimab plus chemotherapy better than T-EC chemotherapy alone in neoadjuvant setting of HR+/HER2-low early stage population? Is SHR-A1811-EC plus Adebrelimab better than T-EC chemotherapy and/or Adebrelimab plus chemotherapy

Participants will:

Take 8 cycles of standard chemotherapy at day1, every 3 weeks cycle(standard care), or take 8 cycles of adebrelimab plus standard chemotherapy at day 1, every 3 weeks cycle(experimental 2), or take 4 cycles of SHR-A1811 and Adebrelimab at day 1, every 3 weeks cycle, then 4 cycles of adebrelimab plus EC chemotherapy at day 1, every 3 weeks cycke(experimental 1).

Visit the clinic once every 6 weeks at neoadjuvant period for tumor assessment. Take surgery after completion of 8 cycles of neoadjuvant therapy and assess the pathological response. Then, visit the clinic once every 12 weeks at first year and then every 6 months for tumor assessment.

Enrollment: 249 estimated patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• ECOG score: 0-1;
• Pathologically confirmed invasive breast cancer, with tumor stage T1c-T2, cN1-2 or T3-4 cN0-2;
• HR positive/HER2 low expression(defined as HER2 IHC 1+/2+, FISH negative);
• Known PD-L1 expression status, or sufficient tumor tissue for PD-L1 testing;
• Sufficient organ function
• Female patients who have not undergone menopause or sterilization, accept for abstain from sexual activity or use an effective contraceptive method during the treatment period and at least 7 months after the last administration of the study medication;
• Voluntarily participate and sign the informed consent form.

Exclusion criteria

• Inflammatory breast cancer;
• Previously received anti-tumor therapy or radiotherapy for any malignant tumor(not including cured cervical carcinoma in situ, basal cell carcinoma or squamous cell carcinoma);
• Concurrently received anti-tumor therapy in other clinical trials, including endocrine therapy, bisphosphonate therapy or immunotherapy;
• Within 4 weeks before enrollment, underwent major surgical procedures unrelated to breast cancer, or the patient has not fully recovered from such procedures;
• Had clinically significant pulmonary diseases, including but not limited to interstitial pneumonia, pneumonia, pulmonary fibrosis and radiation pneumonia (except for radiological changes that do not require treatment), or was found to have such diseases during the screening period;
• Had any cardiac diseases, including: (1) Severe / unstable angina pectoris; (2) Requires drug treatment or has clinically significant arrhythmia; (3) Had a myocardial infarction within 6 months before enrollment; (4) Has symptomatic congestive heart failure with NYHA grade ≥ II; (5) Any other heart diseases judged by the researcher as not suitable for participation in this trial;
• Known to have had an allergic history to the components of the drug in this protocol; have a history of immunodeficiency, including positive HIV test, or have other acquired or congenital immune deficiency diseases, or have a history of organ transplantation;
• Had severe comorbidities or other conditions that would interfere with the planned treatment, or any other situation that the researcher considered the patient was not suitable for participation in this study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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249 participants in 3 patient groups

Arm 1: SHR-A1811-EC + Adebrelimab

Experimental group

Description:

4 cycles of SHR-A1811 follow by 4 cycles of EC chemotherapy, with concurrent adebrelimab throughout all 8 cycles.

Treatment:

Drug: Adebrelimab (PD-L1 inhibitor)

Drug: Anthracycline & Cyclophosphamide treatment scheme

Drug: SHR-A1811

Arm 2: T-EC + Adebrelimab

Experimental group

Description:

4 cycles of taxane follow by 4 cycles of EC chemotherapy, with concurrent adebrelimab throughout all 8 cycles.

Treatment:

Drug: Taxane Chemotherapy

Drug: Adebrelimab (PD-L1 inhibitor)

Drug: Anthracycline & Cyclophosphamide treatment scheme

Arm 3: T-EC

Active Comparator group

Description:

4 cycles of taxane follow by 4 cycles of EC chemotherapy

Treatment:

Drug: Taxane Chemotherapy

Drug: Anthracycline & Cyclophosphamide treatment scheme