Breast Cancer
Conditions
Brief summary
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
Interventions
DRUGSHR-A1811
HER2 ADC
DRUGTROP2 ADC
TROP2 ADC
Sponsors
Fudan University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of adverse events (AEs)- Phase 1 | Up to follow-up period, approximately 24 months | Occurrence of AEs in Phase 1 graded according to CTCAE v5.0 |
| Objective Response Rate (ORR)- Phase 2 | Until progression, assessed up to approximately 24 months | The proportion of patients who have a CR or PR, as determined by the Investigator at local site per RECIST 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DoR) | Until progression, assessed up to approximately 24 months | Time from the date of first documented response until the date of documented progression or death in the absence of disease progression. |
| Disease Control Rate (DCR) | Baseline through end of study, assessed up to 24 months | The proportion of patients who have a CR or PR or SD, as determined by the Investigator at local site per RECIST 1.1. |
| Progression Free Survival (PFS | Until progression, assessed up to approximately 24 months | Time to progression as assessed by the Investigator at local site per RECIST 1.1, or death due to any cause. |
| Exploratory analyses | Baseline until disease progression or loss of clinical benefit, assessed up to 24 months | HER2-PET was done at baseline to further explore the clinical utility of HER2-PET for HER2 detection |
| Safety | Up to follow-up period, approximately 24 months | Occurrence of Adverse Events(AEs) graded according to CTCAE v5.0 |
| Clinical Benefit Rate (CBR) | Until progression or death, assessed up to approximately 24 months | The percentage of subjects with CR, PR and SD≥24 weeks，as determined by the Investigator at local site per RECIST 1.1. |
| Overall Survival (OS) | Until death, assessed up to approximately 24 months | time to death due to any cause |
Countries
China
Outcome results
None listed