T-DM1 Combined With CDK4/6 Inhibitor Ribociclib

Phase II Clinical Study of Trastuzumab Emtansine (T-DM1) Combined With Cyclin-dependent Kinase 4/6 (CDK4/6) Inhibitor Ribociclib in the Treatment of Human Epidermal Growth Factor Receptor-2 (HER2)-Positive Advanced Breast Cancer

To explore the efficacy and safety of T-DM1 combined with CDK4/6 inhibitor Ribociclib in the treatment of HER2-positive advanced breast cancer.

This is a multicenter, single-arm,Phase II clinical trial to explore the efficacy and safety of Trastuzumab Emtansine (T-DM1) combined with CDK4/6 inhibitor Ribociclib in the treatment of unresectable locally advanced or metastatic HER2-positive breast cancer.

Inclusion Criteria:

• Age ≥18 at the time of signing the informed consent.
• Patient's ability to follow the study protocol as determined by the investigator.
• A representative tumor tissue sample is required to confirm a HER2-positive diagnosis.

HER2 expression status and ER expression status of invasive cancer lesions were determined based on previous pathological sections or current pre-treatment biopsy materials, and the HER2 IHC assay was locally confirmed to be consistent with 3+, or IHC assay with 2+, and further FISH detection was positive before study enrollment.

• At least one evaluable lesion was detected by CT or MRI (see protocol for additional details).
• For metastatic or recurrent breast cancer, there is currently no opportunity for surgical radical resection.
• Metastatic or recurrent breast cancer that has received at least first-line rescue therapy in the past must have been treated with trastuzumab and taxanes.
• The Physical status (ECOG) score of the Eastern Tumor Collaboration group was 0 or 1.
• Sufficient haematology and organ function to meet the definition of laboratory test results, which must be provided within 14 days before the start of study therapy.
• Fertile women should remain abstinent (no heterosexual intercourse) or use contraceptive methods.

Exclusion Criteria:

• Past treatment with other antibody-drug conjugate (ADC) drugs or anti-tumor therapy with CDK4/6 inhibitors.
• Past treatment with other anti-HER2 drugs other than trastuzumab, pertuzumab and tyrosine kinase inhibitors (TKI).
• Advanced breast cancer with central nervous system metastasis.
• Patients who have developed other malignancies in the 5 years prior to screening, except adequately treated cervical cancer in situ, non-melanoma skin cancer, localized prostate cancer, ductal carcinoma in situ, or stage I uterine cancer.
• Severe dysfunction of vital organs prior to enrollment (see protocol details).
• Received an investigational drug within 28 days prior to initiation of study therapy.
• Known hypersensitivity or hypersensitivity to CDK4/6 inhibitors.
• The results of the serum pregnancy test were positive.