Different Targeted Antibody-drug Conjugates For HER2 Ultra-low or No Expression Advanced Breast Cancer（GALAXY）

Different Targeted Antibody-drug Conjugates for HER2 Ultra-low or no Expression Advanced Breast Cancer: a Phase Ⅰb/Ⅱ Study（GALAXY）

This is a phaseⅠb/Ⅱ, open-label, two-arm parallel study evaluating the efficacy and safety of different targeted antibody-drug conjugates for HER2 ultra-low or no expression advanced breast cancer

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: SHR-A1811; Drug: TROP2 ADC

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

ECOG Performance Status of 0 or 1

Pathologically documented breast cancer that:

1. is advanced or metastatic
2. is histologically confirmed to be HER2 IHC 0 (ISH- or untested)
3. was never previously HER2-positive (IHC 3+ or ISH+) At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.

Disease progression on at least 1 previous line of chemotherapy for recurrent/metastatic breast cancer. Subjects with HER2-negative and hormone-receptor positive tumors must have progressed after at least 1 line of endocrine therapy with or without CDK4/6 inhibitor.

Has protocol-defined adequate organ and bone marrow function. Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

Has previously been treated with any anti-HER2 therapy. Known prior severe hypersensitivity to investigational product or any component in its formulation and other monoclonal antibodies.

Any major surgery, radiotherapy, chemotherapy, immunotherapy or molecular targeted therapy, biotherapy or other drug clinical trial within 4 weeks; received endocrine therapy within 2 weeks before the first study drug administration.

History of other malignancy than breast cancer within 5 years prior to screening (except for cured skin basal cell carcinoma and cervical carcinoma in situ).

Meningeal metastasis or active brain parenchymal metastasis. Any concurrent use of immunosuppressant or systemic corticosteroid treatment to achieve immunosuppression purpose (dose of > 10mg/day prednisone or equivalent), and still in use within 2 weeks before the first study drug administration.

Has uncontrolled intercurrent illness or significant cardiovascular disease. History of clinically significant lung diseases. History of immunodeficiency, including HIV positive. Known active hepatitis B virus or hepatitis C virus infection. Has any medical history or condition that per protocol or in the opinion of the investigator is inappropriate for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: HER2 ADC; Patients diagnosed with HER2 ultra-low or no expression are recruited	Drug: SHR-A1811; HER2 ADC
Experimental: Experimental: TROP2 ADC; Patients diagnosed with HER2 ultra-low or no expression are recruited.	Drug: TROP2 ADC; TROP2 ADC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of adverse events (AEs)- Phase 1	Occurrence of AEs in Phase 1 graded according to CTCAE v5.0	Up to follow-up period, approximately 24 months
Objective Response Rate (ORR)- Phase 2	The proportion of patients who have a CR or PR, as determined by the Investigator at local site per RECIST 1.1.	Until progression, assessed up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS	Time to progression as assessed by the Investigator at local site per RECIST 1.1, or death due to any cause.	Until progression, assessed up to approximately 24 months
Overall Survival (OS)	time to death due to any cause	Until death, assessed up to approximately 24 months
Duration of Response (DoR)	Time from the date of first documented response until the date of documented progression or death in the absence of disease progression.	Until progression, assessed up to approximately 24 months
Disease Control Rate (DCR)	The proportion of patients who have a CR or PR or SD, as determined by the Investigator at local site per RECIST 1.1.	Baseline through end of study, assessed up to 24 months
Clinical Benefit Rate (CBR)	The percentage of subjects with CR, PR and SD≥24 weeks，as determined by the Investigator at local site per RECIST 1.1.	Until progression or death, assessed up to approximately 24 months
Safety	Occurrence of Adverse Events(AEs) graded according to CTCAE v5.0	Up to follow-up period, approximately 24 months
Exploratory analyses	HER2-PET was done at baseline to further explore the clinical utility of HER2-PET for HER2 detection	Baseline until disease progression or loss of clinical benefit, assessed up to 24 months

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2023
• Primary Completion (Estimated): April 10, 2025
• Study Completion (Estimated): October 10, 2026

Study Registration Dates

• First Submitted: March 5, 2023
• First Submitted That Met QC Criteria: April 11, 2023
• First Posted (Actual): April 21, 2023

Study Record Updates

• Last Update Posted (Actual): June 27, 2023
• Last Update Submitted That Met QC Criteria: June 25, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: GALAXY

Drug and device information, study documents

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