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.

Study Overview

• Status: Enrolling by invitation
• Conditions: HER2-positive Advanced Breast Cancer
• Intervention / Treatment: Drug: Ribociclib Oral Tablet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital

Participation Criteria

Eligibility Criteria

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

Description

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.

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: T-DM1 combined with Ribociclib; Enrolled patients will receive (repeat every 21 days) : ● T-DM1 3.6 mg/kg d1;● Ribociclib 400 mg qd, d8-d21; * ER-positive patients will receive endocrine therapy at the same time: aromatase inhibitors or fulvestrant , and ovarian suppression or ovariectomy in premenopausal women.

Drug: Ribociclib Oral Tablet; Patients with advanced breast cancer with at least one evaluable lesion and histologically proven invasive breast cancer were eligible for inclusion. Histopathologically positive for HER2 (IHC 3+, or IHC 2+ with fluorescence in situ hybridization (FISH) positive, either primary or metastatic. Patients with advanced breast cancer must have previously received first-line therapy or initial rescue therapy and have been treated with trastuzumab against HER2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as the percentage of patients who achieved a best overall response of Complete Response (CR) or Partial Response (PR), per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions as assessed by the Investigator: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.	up to 54 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	From date of first dose until the date of first documented progression or date of death from any cause, whichever came first.	up to 54 months
2-year Overall Survival (OS)	the overall survival rate in all patients from the date of first dose to the end of follow-up at 2 years.	up to 54 months
Objective Response Rate of Subgroup Population (ORR)	Objective Response Rate of subgroup population (ER>=10% vs ER<10%)	up to 54 months
Adverse Event (AE)	Evaluation performed using the National Cancer Institute (NCI)- Standard for Common Terminology for Adverse Events (CTCAE)v.5.0.	up to 54 months

Collaborators and Investigators

• Sponsor: Zheng Yabing
• Investigators: Principal Investigator: Yabing Zheng, MD, Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2023
• Primary Completion (Estimated): January 10, 2027
• Study Completion (Estimated): October 10, 2027

Study Registration Dates

• First Submitted: June 25, 2024
• First Submitted That Met QC Criteria: June 25, 2024
• First Posted (Actual): July 1, 2024

Study Record Updates

• Last Update Posted (Actual): July 1, 2024
• Last Update Submitted That Met QC Criteria: June 25, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Ribociclib; HER2-positive; Advanced breast cancer; Trastuzumab Emtansine
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: [2023]-06-10

Drug and device information, study documents

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