FS-1502 Versus T-DM1 for HER2-Positive Unresectable Locally Advanced or Metastatic Breast Cancer

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05755048
• Other study ID #: FS-1502-III1-01
• Status: Recruiting
• Phase: Phase 3
• Start date: March 28, 2023
• Est. completion date: January 31, 2026

Study information

• Verified date: February 2023
• Source: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.
• Contact: Binghe Xu, MD
• Phone: 13501028690
• Email: xubingheBM[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 314
• Est. completion date: January 31, 2026
• Est. primary completion date: July 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• Investigational drug: Recombinant Anti-HER2 Humanized Monoclonal Antibody - Monomethyl Auristatin F Conjugates for Injection (FS-1502)
Experimental: FS-1502 Dosage form: lyophilized powder Specification: 30 mg/vial Dose: 2.3 mg/kg, once every 3 weeks, 21 days as a cycle; Method of administration: intravenous drip.
• Control drug: Trastuzumab emtansine (Kadcyla, T-DM1)
Active Comparator: Trastuzumab Emtansine (T-DM1) Trade name: Kadcyla Dosage form: lyophilized powder Specification: 100 mg/vial Dose: 3.6 mg/kg, once every 3 weeks, 21 days as a cycle; Method of administration: intravenous drip (this drug has been approved for marketing. Please refer to the package insert for details).

Locations

Country	Name	City	State
China	AnYang Cancer Hospital	AnYang	Henan
China	Affiliated Hospital of Hebei University	Baoding	Hebei
China	Chinese People's Liberation Army General Hospital fifth Medical Center South ward	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	The first affiliated hospital of bengbu medical college	Bengbu	Anhui
China	Cangzhou Central Hospital	Cangzhou	Hebei
China	First Hospital of Jilin University	Changchun	Jilin
China	Jilin Cancer Hospital	Changchun	Jilin
China	The Second Xiangya Hospital, Central South University	Changsha	Hunan
China	West China Hospital,Sichuan University	Chengdu	Sichuan
China	Chenzhou No.1 People's Hospital	Chenzhou	Hunan
China	Affiliated Cancer Hospital of Chongqing University	Chongqing	Chongqing
China	Chinese People's Liberation Army Army Special Medical Center	Chongqing	Chongqing
China	The Second Affiliated Hospital of Dalian Medical University	Dalian	Liaoning
China	Fujian Cancer Hospital	Fuzhou	Fujian
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	The 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army	Fuzhou	Fujian
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	The First Affiliated Hospital,Sun Yat-sen University	Guangzhou	Guangdong
China	The Second Affiliated Hospital Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Anhui Provincial Cancer Hospital	Hefei	Anhui
China	Shandong First Medical University and Shandong Academy of Medical Sciences Shandong Cancer Hospital institute	Jinan	Shandong
China	Affiliated Hospital of Jining Medical University	Jining	Shandong
China	Yunnan Cancer Hospital	Kunming	Yunnan
China	The first Hospital of lanzhou University	Lanzhou	Gansu
China	Linyi Cancer Hospital	Linyi	Shandong
China	Affiliated Hospital of Southwest Medical University	Luzhou	Sichuan
China	Nanchang People's Hospital	Nanchang	Jiangxi
China	Jiangsu Cancer Hospital	Nanjing	Jiangsu
China	Jiangsu Province Hospital	Nanjing	Jiangsu
China	Guangxi Medical Univesity Cancer Hospital	Nanning	Guangxi
China	The First Afeliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Neijiang Second People's Hospital	Neijiang	Sichuan
China	Shantou University School of Medicine Affiliated Cancer Hospital	Shantou	Guangdong
China	Liaoning cancer hospital & institute	Shenyang	Liaoning
China	The first hospital of china medical university	Shenyang	Liaoning
China	Cancer Hospital Chinese Academy of Medical Sciences,Shenzhen Center	Shenzhen	Guangdong
China	The Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei
China	Shanxi Cancer Hospital	Taiyuan	Shanxi
China	TianJin Medical university Cancer Institute & Hospital	TianJin	Tianjin
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Renmin Hospital Of Wuhan University	Wuhan	Hubei
China	Union Hospital, Tongji Medical College, Huazhong University of Science and Technology	Wuhan	Hubei
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei
China	The first affiliated hospital of xiamen university	Xiamen	Fujian
China	The First Affiliated Hospital of Xi'an Jiaotong University	Xian	Shanxi
China	Xiangyang Central Hospital	Xiangyang	Hubei
China	The First Affiliated Hospital of Xinxiang Medical University	Xinxiang	Henan
China	The Affiliated Hospital of Xuzhou Medical University	Xuzhou	Jiangsu
China	General Hospital of Ningxia Medical University	Yinchuan	Ningxia
China	The Central Hospital of Yongzhou	Yongzhou	Hunan
China	Henan Cancer Hospital	Zhengzhou	ZHenan
China	Henan Provincial People's Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Progression-free survival (PFS) by ICR was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.	Up to 28 months.
Secondary	Overall Survival (OS) in Participants With HER2-Positive, Unresectable locally advanced or Metastatic Breast Cancer Previously Treated With Trastuzumab and Taxane.	Overall survival (OS) was defined as the time from the date of first dose of study drug to the date of death due to any cause.	Up to 28 months.
Secondary	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.	Objective Response Rate (ORR) was defined as the percentage of participants who achieved a best overall response of confirmed Complete Response (CR) or Partial Response (PR), assessed by ICR and investigator assessment based on RECIST version 1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. Confirmed ORR is reported.	Up to 28 months.
Secondary	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.	DCR confirmed by IRC or investigator evaluation is defined as the proportion of patients with objective remission (CR or PR) or stable disease (SD) confirmed by IRC or investigator.	Up to 28 months.
Secondary	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.	CBR confirmed by IRC or investigator evaluation is defined as the proportion of patients with confirmed CR, PR and SD lasting = 24 weeks evaluated by IRC or investigator according to RECIST version 1.1.	Up to 28 months.
Secondary	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.	Duration of Response (DOR) was defined as the time from the date of the first documentation of objective response (complete response [CR] or partial response [PR]) to the date of the first objective documentation of progressive disease (PD) or death due to any cause. DOR in participants with confirmed CR/PR based on BICR and investigator assessment is reported.	Up to 28 months.
Secondary	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.	Progression-free survival (PFS) by investigator assessment was defined as the time from the date of enrollment to the earlier of the dates of the first objective documentation of disease progression (as per RECIST v1.1) or death due to any cause. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.	Up to 28 months.
Secondary	Treatment-emergent adverse events (TEAEs).	Type and frequency of treatment-emergent adverse events (TEAEs) with toxicity grades evaluated according to the National Cancer Institute-Common Toxicity Criteria Adverse Event (NCI-CTCAE) version 5.0.	Up to 28 months.