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

Official title

Chemotherapy Combine With or Without Adebrelimab and Trastuzumab Rezetecan(SHR-A1811) as Neoadjuvant Therapy for Hormone Receptor Positive/HER2 Low Early Stage Breast Cancer: A Randomized Phase II Trial

Overview

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.

Interventions

• Drug SHR-A1811
  An anti-HER2 ADC injection, administered on day 1 of each cycle, with one cycle every 3 weeks. 4.8mg/kg or 5.6mg/kg IV, according to the outcomes of the safety run in process.
• Drug Adebrelimab (PD-L1 inhibitor)
  A PD-L1 inhibitor, 1200mg IV, is administered on the 1st day of every 3 weeks cycle.
• Drug Taxane Chemotherapy
  Could be paclitaxel, docetaxel or Nab-paclitaxel, according to physician's choice.
• Drug Anthracycline & Cyclophosphamide treatment scheme
  Anthracycline usually use epirubicin, 90-100mg/m2, combine with Cyclophosphamide 600mg/m2, both use at day 1, every 3 weeks cycle.

Primary outcome measures

• tpCR(ypT0/Tis ypN0M0) [Time frame: After surgery (within 1 month)]

Secondary outcome measures (3)

• EFS [Time frame: from enrollment to completion of 3 years of follow up after surgery]
• OS [Time frame: from enrollment to complete of 5 years follow up after surgery]
• Adverse Events [Time frame: AEs were assessed from enrollment throughout the trial and for 30 days after discontinuation of treatment (90 days for serious AEs)]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• National Cancer Center/Cancer hospital, Chinese Academy of Medical Sciences and Peking Uni — Beijing

Identifiers

NCT: NCT07317778 · MA-BC-II-094

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗