A Phase III Study of SKB264 for Locally Advanced, Recurrent or Metastatic HR+/HER2- Breast Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of SKB264 in patients with unresectable locally advanced, recurrent, or metastatic HR+/HER2- breast cancer.

Detailed Description
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This is a randomized, open-label, multicenter Phase 3 clinical study to evaluate SKB264 monotherapy versus Treatment of Physician's Choice (TPC) in subjects with unresectable locally advanced, recurrent, or metastatic HR+/HER2- breast cancer who had failed at least one line of systemic chemotherapy.

Official Title
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A Randomized, Open-label, Multicenter Phase 3 Study of SKB264 Versus Treatment of Physician's Choice (TPC) in Patients With Unresectable Locally Advanced, Recurrent or Metastatic HR+/HER2- Breast Cancer Who Had Failed at Least One Line of Chemotherapy

Conditions
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Metastatic Breast Cancer

Intervention / Treatment
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* Drug: SKB264
* Drug: Eribulin
* Drug: Capecitabine
* Drug: Gemcitabine
* Drug: Vinorelbine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females aged ≥ 18 to ≤ 75 years at the time of signing the ICF; Histologically and/or cytologically confirmed HR+/HER2- breast cancer based on pathology reports on recent biopsy specimens or other pathological samples; Patients who had failed at least one line of systemic chemotherapy in unresectable locally advanced, recurrent, or metastatic stage; Patients with at least one measurable lesion per RECIST 1.1 criteria; those with only skin or bone lesions cannot be included; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1; Expected survival ≥ 12 weeks; Adequate organ and bone marrow function; Patients who are eligible for a chemotherapy regimen in the control group; Female patients of childbearing potential and male patients with partners of childbearing potential who use effective medical contraception from the time of signing the informed consent form until 6 months after the last dose; Patients who voluntarily participate in the study and sign the ICF, and able to comply with the visit and related procedures stipulated in the plan. Exclusion Criteria: Patients with a history of central nervous system (CNS) metastases or current CNS metastases； Patients with other malignancies (except cured basal or squamous cell skin cancer or carcinoma in situ of the cervix) within 3 years prior to the first dose; Patients with any cardio cerebral Vascular disease or cardio cerebral vascular risk factors may affect investigational treatment; Uncontrollable systemic diseases assessed by the investigator; History of (noninfectious) interstitial lung disease (ILD)/noninfectious neumonitis requiring steroid therapy and current ILD/noninfectious pneumonitis, or ILD/noninfectious pneumonitis at screening that cannot be excluded by imaging; Clinically serious lung injuries caused by lung diseases; Patients with active chronic Inflammatory bowel disease, gastrointestinal obstruction, severe ulcer, gastrointestinal perforation, abdominal abscess or acute gastrointestinal bleeding; Toxicities from prior anti-tumor therapy not recovering to ≤ Grade 1; Active hepatitis B or hepatitis C; Human immunodeficiency virus (HIV) antibody test positive or a history of acquired immunodeficiency syndrome (AIDS), known active syphilis infection; Known allergy or hypersensitivity to SKB264, or the excipients of SKB264; Prior TROP2 targeted therapy, prior topoisomerase I inhibitor therapy, including antibody-drugconjugate(ADC) therapy; Patients who received major surgeries 4 weeks prior to the first dose of study treatment or planned to receive major surgeries during the study ; Patients with concomitant infections requiring systemic antibiotic therapy within 2 week prior to the first dose of study treatment; Patients who have received live vaccines within 30 days prior to the first dose, or are scheduled to receive live vaccines during the study; Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SKB264 for injection<br> | Drug: SKB264<br>* IV infusion on day 1 and Day 15 of each 28 day cycle<br>|
| Active Comparator: Treatment of Physician's Choice<br>Eribulin, capecitabine, gemcitabine or vinorelbine will be administered and managed according to the investigator's clinical judgment, guided by clinical practice. | Drug: Eribulin<br>* 1.4 mg/m2, IV infusion on day 1 and Day 8 of each 21 day cycle<br>Drug: Capecitabine<br>* 1000-1250 mg/m2, po, bid, from day 1 to Day 15 of each 21 day cycle<br>Drug: Gemcitabine<br>* 1000 mg/m2, IV infusion on day 1 and Day 8 of each 21day cycle<br>Drug: Vinorelbine<br>* 25 mg/m2, IV infusion on day 1 and Day 8 of each 21 day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) assessed by BIRC per RECIST 1.1. | PFS, defined as the time from randomization to PD or death, whichever occurs first. | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS, defined as the time from randomization to death | up to 24 months | 
| Progression-free survival (PFS) assessed by the investigators per RECIST V 1.1 | PFS, defined as the time from randomization to PD or death, whichever occurs first. | up to 24 months | 
| Objective Response Rate (ORR) | The percentage of patients with CR and PR assessed by BIRC and investigators per RECIST v 1.1 | up to 24 months | 
| Disease Control Rate (DCR) | The percentage of patients who have achieved CR，PR and SD assessed by BIRC and investigators per RECIST v 1.1 | up to 24 months | 
| Duration of Response (DoR) | From the date that response criteria are first met to the first occurrence of PD as determined by BIRC and investigators per RECIST v1.1 or death from any cause, whichever occurs first | up to 24 months | 
| Quality of life of patients evaluated using the EORTC QLQ-C30 scale | To assess the impact of SKB264 on disease related symptoms and health related quality of life (HRQoL) in this patient population | Up to 2 years | 
| AEs and SAEs | Incidence and severity of AEs and SAEs (per CTCAE 5.0), and clinically significant abnormal laboratory findings | AEs should be observed and recorded from signing the ICF until 30 days after the last dose. AEs occurring 30 days after the last dose are not required to be actively collected by the investigator. |