Clinical trial NCT05755048: FS-1502 Versus T-DM1 for HER2-Positive Unresectable Locally Advanced or Metastatic Breast Cancer
Official title: A Multicenter, Open-label, Randomized Controlled Phase III Clinical Study to Compare the Efficacy and Safety of FS-1502 Versus T-DM1 in Patients With HER2-positive Unresectable Locally Advanced or Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2023-03-06
Enrollment: 314
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to compare the anti-tumor activity as well as the safety and efficacy of FS-1502 versus T-DM1 in HER2-positive, unresectable locally advanced or metastatic breast cancer subjects previously treated with trastuzumab and taxane.

Detailed description: This study is a multicenter, open-label, randomized controlled phase III clinical study to compare the efficacy and safety of FS-1502 versus T-DM1 in patients with HER2-positive unresectable locally advanced or metastatic breast cancer. Patients who meet the inclusion and exclusion criteria will be randomized into the test group (FS-1502) or control group (T-DM1) in a 1:1 ratio. Patients in the test group will receive FS-1502 2.3 mg/kg, and those in the control group will receive T-DM1 3.6 mg/kg, by intravenous drip every 3 weeks. Patients will be treated until disease progression (PD), intolerable toxicity, withdrawal of consent, death, or other protocol-specified reasons. According to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1), tumor assessment will be performed every 6 weeks (± 7 days) for the first 12 months and every 12 weeks (± 7 days) after 12 months until PD, withdrawal of consent, or death. Efficacy evaluation will be performed by the investigator and the Independent Review Committee (IRC), respectively.

Eligibility criteria: Inclusion Criteria:Subjects are eligible to be included in the study only if they meet all of the following criteria:

1. Male or female age ≥ 18;
2. Histologically or cytologically confirmed HER2-positive unresectable locally advanced or metastatic breast cancer;
3. Prior treatment with trastuzumabs and taxanes in the adjuvant therapy, neoadjuvant therapy, or advanced treatment phases;
4. ≥ 1 and ≤ 3 previous lines of therapy against locally advanced or metastatic diseases, if PD occurring during adjuvant therapy/neoadjuvant therapy and within 12 months after treatment can be taken as one line of therapy;
5. Tissue samples qualified by the central laboratory for HER2 detection are available, and HER2 is confirmed positive by the pathology test in the central laboratory: Immunohistochemistry (IHC) 3+, or IHC2+ and fluorescence in situ hybridization (FISH)+ as the basis for inclusion;
6. ECOG score at 0 or 1;
7. Expected survival ≥ 12 weeks;
8. Adequate organ and bone marrow functions: absolute neutrophil count \[ANC\] ≥1.0×10\^9/L (no use of granulocyte-colony-stimulating factor (G-CSF) within 7 days); hemoglobin (HGB) ≥ 90 g/L (no red blood cell transfusion within 14 days); platelet count (PLT) ≥ 100×10\^9/L (no use of platelet-elevating drugs within 7 days, no platelet transfusion within 14 days); total serum bilirubin (TSB) ≤ 1.5 × upper limit of normal (ULN) or ≤ 3.0 × ULN for patients with Gilbert syndrome; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5×ULN; for patients with liver metastases, AST and ALT ≤ 5×ULN; creatinine clearance ≥ 50 mL/min (calculated by Cockroft-Gault formula); blood potassium ≥3.5 mmol/L; albumin ≥ 3 g/dL; left ventricular ejection fraction (LVEF) \>50%; urine protein ≤1+ or 24h urine protein quantification \<1.0 g;
9. At least one non-intracranial evaluable lesion as assessed by RECIST 1.1;
10. Female patients of childbearing potential must agree to take highly effective contraceptive measures or avoid sexual intercourse during and after the study and within at least 3 months after the last dose of FS-1502 and within at least 7 months after the last dose of T-DM1. Male patients must agree to avoid sexual intercourse, or they and/or any female partners of childbearing potential must take a medically acceptable and effective contraceptive measure, such as double barrier methods, condoms, oral or injectable contraceptives, intra-uterine devices during and after the study and within at least 3 months after the last dose of FS-1502 or within at least 4 months after the last dose of T-DM1;
11. Be able to understand and voluntarily sign the written Informed Consent Form (ICF).

Exclusion Criteria:

Patients that meet any of the following conditions shall not be included in this clinical study:

1. Patients who have received chemotherapy, small molecule targeted drug therapy, endocrinotherapy，radiotherapy, etc. within 14 days or 5 half-lives (whichever is shorter) before administration or who have received major surgical treatment and tumor immunotherapy within 4 weeks before administration or who have received large molecule monoclonal antibody drugs for cancer treatment within 21 days before administration.
2. Patients who have participated in other clinical studies within 4 weeks or 5 half-lives of the drug (whichever is shorter) before administration.
3. Patients who have been previously treated with anti-HER2 ADCs for metastatic diseases.
4. Patients with known hypersensitivity or delayed type hypersensitivity to certain ingredients of T-DM1 or similar drugs, or with known contraindications for the use of T-DM1.
5. Patients with pia maters, spinal cords, brainstem and brain parenchymal metastases; such patients are allowed to be enrolled if all of the following conditions are met:

   1. Patients who have received local treatment and the lesions are stable for more than 6 months;
   2. Patients who have no clinical symptoms and don't need glucocorticoid therapy or other dehydration treatment, and have a stable dose of an antiepileptic drug, if applicable.
6. Patients with a large quantity of clinically uncontrolled pleural effusion, pericardial effusion, or ascites (within 2 weeks prior to the first dose).
7. Unresolved toxic reactions from previous anti-tumor therapy (\> NCI-CTCAE 5.0 Grade 1); however, alopecia, neurotoxicity or other toxicity that has converted to chronic and returned to NCI-CTCAE 5.0 Grade ≤ 2, and does not affect the safety of the patient as assessed by the Investigator are allowed to be enrolled.
8. History of non-infectious interstitial lung disease (ILD) / pneumonia, current ILD / pneumonia, or imaging suggestive of suspected moderate-severe ILD / pneumonia at screening.
9. Subjects with corneal epithelial lesions (except mild punctate keratopathy), or other ocular diseases that affect the evaluation of ocular toxicity after the investigational product administration, or unwilling to stop wearing corneal contact lenses during the study.
10. Patients on medications that prolong the QTc interval (mainly Classes Ia, Ic, III anti- arrhythmia medications) or with risk factors for prolonging the QTc interval, such as uncorrectable hypokalemia, inherited long QT syndrome; potential medications for prolonging the QTc interval are presented in Appendix 7.
11. Cardiac function and diseases that meet one of the following conditions:

    1. Mean QTc \> 450 ms for males and mean QTc \> 470 ms for females averaged from 3 results of 12-lead ECG measurements using the QTcF formula of the ECG instrument at the study site during the screening period;
    2. New York Heart Association (NYHA) Functional Classification ≥ Class 2 congestive heart failure;
    3. Clinically significant arrhythmia (Grade ≥ 2);
    4. History of myocardial infarction or severe arteriovenous thrombotic events within 6 months.
12. Pregnant or breastfeeding women.
13. Known hypersensitivity to any excipients of FS-1502.
14. Active infection requiring systemic therapy.
15. Active hepatitis B (positive for HBV surface antigen and detected with HBV DNA \> 1000 IU/mL or meeting the diagnostic criteria for active hepatitis B infection at the study site) or hepatitis C (positive for HCV RNA) and human immunodeficiency viral infection (HIV positive).
16. Any other malignancy diagnosed within 5 years prior to the study, except for early malignancies (carcinoma in situ) that have undergone radical treatment, such as adequately treated basal or squamous cell skin cancer or cervical carcinoma in situ.
17. Any other diseases or conditions considered clinically significant by the investigator that could affect protocol compliance or affect the patient's ability to sign the ICF.

Primary outcomes:
measure: Progression-Free Survival (PFS) Based on Independent Central Review (ICR) in Participants With HER2-Positive, Unresectable locally advanced or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane.
timeFrame: Up to 28 months.
Secondary outcomes:
measure: Overall Survival (OS) in Participants With HER2-Positive, Unresectable locally advanced or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane.
timeFrame: Up to 28 months.
measure: Objective Response Rate (ORR) Based on ICR and Investigator Assessment in Participants With HER2-Positive, Unresectable locally advanced or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane.
timeFrame: Up to 28 months.
measure: Disease control rate (DCR) Based on ICR and Investigator Assessment in Participants With HER2-Positive, Unresectable locally advanced or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane.
timeFrame: Up to 28 months.
measure: Clinical benefit rate (CBR) Based on ICR and Investigator Assessment in Participants With HER2-Positive, Unresectable locally advanced or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane.
timeFrame: Up to 28 months.
measure: Duration of overall response (DOR) Based on ICR and Investigator Assessment in Participants With HER2-Positive, Unresectable locally advanced or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane.
timeFrame: Up to 28 months.
measure: Progression-Free Survival (PFS) Based on Investigator Assessment in Participants With HER2-Positive, Unresectable locally advanced or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane.
timeFrame: Up to 28 months.
measure: Treatment-emergent adverse events (TEAEs).
timeFrame: Up to 28 months.
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The first affiliated hospital of bengbu medical college
state: Anhui
city: Hefei
country: China
facility: Anhui Provincial Cancer Hospital
state: Anhui
city: Beijing
country: China
facility: Chinese People's Liberation Army General Hospital fifth Medical Center South ward
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Chongqing
country: China
facility: Affiliated Cancer Hospital of Chongqing University
state: Chongqing
city: Chongqing
country: China
facility: Chinese People's Liberation Army Army Special Medical Center
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Fuzhou
country: China
facility: The 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army
state: Fujian
city: Xiamen
country: China
facility: The first affiliated hospital of xiamen university
state: Fujian
city: Lanzhou
country: China
facility: The first Hospital of lanzhou University
state: Gansu
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital,Sun Yat-sen University
state: Guangdong
city: Shantou
country: China
facility: Shantou University School of Medicine Affiliated Cancer Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences,Shenzhen Center
state: Guangdong
city: Nanning
country: China
facility: Guangxi Medical Univesity Cancer Hospital
state: Guangxi
city: Nanning
country: China
facility: The First Afeliated Hospital of Guangxi Medical University
state: Guangxi
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
city: Cangzhou
country: China
facility: Cangzhou Central Hospital
state: Hebei
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: AnYang
country: China
facility: AnYang Cancer Hospital
state: Henan
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical University
state: Henan
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Wuhan
country: China
facility: Renmin Hospital Of Wuhan University
state: Hubei
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Xiangyang
country: China
facility: Xiangyang Central Hospital
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital, Central South University
state: Hunan
city: Chenzhou
country: China
facility: Chenzhou No.1 People's Hospital
state: Hunan
city: Yongzhou
country: China
facility: The Central Hospital of Yongzhou
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Nanchang
country: China
facility: Nanchang People's Hospital
state: Jiangxi
city: Changchun
country: China
facility: First Hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Dalian
country: China
facility: The Second Affiliated Hospital of Dalian Medical University
state: Liaoning
city: Shenyang
country: China
facility: Liaoning cancer hospital & institute
state: Liaoning
city: Shenyang
country: China
facility: The first hospital of china medical university
state: Liaoning
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Jinan
country: China
facility: Shandong First Medical University and Shandong Academy of Medical Sciences Shandong Cancer Hospital institute
state: Shandong
city: Jining
country: China
facility: Affiliated Hospital of Jining Medical University
state: Shandong
city: Linyi
country: China
facility: Linyi Cancer Hospital
state: Shandong
city: Taiyuan
country: China
facility: Shanxi Cancer Hospital
state: Shanxi
city: Xian
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital，Sichuan University
state: Sichuan
city: Luzhou
country: China
facility: Affiliated Hospital of Southwest Medical University
state: Sichuan
city: Neijiang
country: China
facility: Neijiang Second People's Hospital
state: Sichuan
city: TianJin
country: China
facility: TianJin Medical university Cancer Institute & Hospital
state: Tianjin
city: Kunming
country: China
facility: Yunnan Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: ZHenan
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Binghe Xu, MD
role: PRINCIPAL_INVESTIGATOR
References: