Metastatic Breast Cancer
Conditions
Keywords
SKB264, HR+/HER2- breast cancer
Brief summary
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 who have previously failed endocrine therapy.
Detailed description
This is a randomized, open-label, multicenter phase 3 clinical study to evaluate the efficacy and safety of SKB264 monotherapy versus investigator's choice of chemotherapy (ICC) in subjects with unresectable locally advanced, recurrent, or metastatic HR+/HER2- breast cancer who had failed at least one line of systemic chemotherapy and have not recieved systemic chemotherapy for locally advanced, relapsed, or metastatic stages.
Interventions
DRUGPaclitaxel
90 mg/m\^2, IV, on Days 1, 8, and 15 every 4 weeks; or 80 mg/m\^2, IV, weekly, every 3 weeks
DRUGCapecitabine
1000-1250 mg/m\^2, orally, Days 1-14, twice daily, every 3 weeks
DRUGSKB264
5mg/kg, IV on Day 1 and Day 15 of each 28 day cycle
DRUGNab-paclitaxel
100 mg/m\^2, IV, on Days 1, 8, and 15 every 4 weeks
Sponsors
Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants will be randomised in a 1:1 ratio to one of two intervention groups
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Aged ≥ 18 and ≤ 75 years at the time of signing the ICF, male or female; 2. Histologically and/or cytologically confirmed HR+/HER2- BC based on pathological reports from the most recent biopsy or other pathological specimens; 3. Subjects must have radiologically documented disease progression during or after the most recent treatment prior to enrollment; 4. No prior systemic chemotherapy for locally advanced, relapsed, or metastatic stages. Subjects who previously received adjuvant/neoadjuvant chemotherapy and progressed \>6 months after completion of the last chemotherapy treatment will be allowed for study inclusion; 5. The investigator assessed that the patient could not continue to benefit from endocrine therapy and was suitable for receiving first-line chemotherapy; 6. Able to provide recently newly obtained or archival tumor tissue sections at or after diagnosis of relapsed or metastatic tumor within the recent prior to randomization; 7. At least one measurable lesion per RECIST v1.1； 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 with no worsening within 2 weeks prior to randomization; 9. Life expectancy of ≥ 12 weeks; 10. Suitable to receive one of the chemotherapy regimens listed in the investigator's choice of chemotherapy (paclitaxel, nab-paclitaxel, capecitabine) as assessed by the investigator; 11. Adequate organ and bone marrow function; 12. Having recovered from all toxicities due to prior treatment; 13. Use of effective medical contraception during study treatment and for 6 months after the end of dosing for female subjects of childbearing potential and male subjects with partners of childbearing potential; 14. Willingness to participate in the study, sign the ICF, and comply with the protocol-specified visits and relevant procedures.
Exclusion criteria
1. Subjects with locally advanced breast cancer suitable for curative therapy at study enrollment; 2. Other malignancies (except those tumors cured by local treatment, such as basal cell carcinoma of skin, squamous cell carcinoma of skin, carcinoma in situ of the cervix) within 3 years prior to randomization; 3. Subiects with known meningeal metastases, brainstem metastases, spinal cord metastases and/or compression or active centralnervous system (CNS) metastases. 4. Presence of any serious cardiovascular and cerebrovascular diseases or cardiovascular and cerebrovascular risk factors; 5. History of (noninfectious) interstitial lung disease (ILD)/noninfectious pneumonitis requiring steroid therapy and current ILD/noninfectious pneumonitis, or suspected ILD/noninfectious pneumonitis at screening that cannot be excluded by imaging; 6. Clinically serious lung injuries caused by lung diseases; 7. Serious infection within 4 weeks prior to randomization, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; active infection requiring systemic anti-infective therapy within 2 weeks prior to randomization; 8. Documented severe dry eye syndrome, severe meibomian gland dysfunction and/or blepharitis, or history of severe corneal disorders that prevent/delay corneal healing; 9. History of esophagogastric varices, severe ulcers, gastric perforation, gastrointestinal obstruction, intra-abdominal abscess, or acute gastrointestinal bleeding within 6 months prior to randomization; 10. Active hepatitis B (hepatitis B surface antigen positive and HBV-DNA ≥ 500 IU/mL or above the ULN, whichever is higher) or hepatitis C (hepatitis C antibody positive and HCV-RNA above the ULN); 11. Positive result of human immunodeficiency virus (HIV) test or history of acquired immunodeficiency syndrome (AIDS); known active syphilis infection; 12. 12 Known hypersensitivity to SKB264 or investigator's choice chemotherapy or any of its excipients, including but not limited to polysorbate-20, or history of severe hypersensitivity reaction to other monoclonal antibodies; 13. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation. 14. Pregnant or lactating women; 15. Prior TROP2-targeted therapy or any treatment containing chemotherapeutic agents targeting topoisomerase I (including antibody-drug conjugates \[ADCs\]); 16. Live vaccines within 4 weeks prior to randomization or scheduled to receive live vaccines during study treatment; 17. Receipt of the following therapies prior to randomization: a)Major surgery within 4 weeks prior or expected major surgery during the study; b)Radiation therapy within 2 weeks prior (extensive radiation therapy including radiopharmaceuticals within 4 weeks prior); c)Any immunotherapy, biological therapy, or other investigational drugs within 4 weeks or 5 half-lives of prior drug use (whichever is shorter) (bisphosphonates or RANK-L inhibitors for bone metastases are permitted prior to randomization); or traditional Chinese medicine with approved anti-tumor indications, small molecule targeted therapy, or endocrine therapy within 2 weeks prior. 18. Rapid deterioration of the condition, e.g., significant changes in performance status, etc., during the screening process.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) assessed by Blinded Independent Central Review (BICR) | Randomization up to approximately 24 months | PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR or death due to any cause, whichever occurs first |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Randomization up to approximately 67 months | OS is defined as the time from randomization until the date of death due to any cause |
| Progression-Free Survival (PFS) assessed by Investigator | Randomization up to approximately 24 months | PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on investigator or death due to any cause, whichever occurs first. |
| Objective Response Rate (ORR) | Randomization up to approximately 24 months | ORR is defined as the percentage of patients who achieve complete response(CR) or partial response (PR), as assessed by BICR/investigator per RECIST 1.1 |
| Disease control rate (DCR) | Randomization up to approximately 24 months | DCR is defined as the percentage of patients who achieve CR, PR or stable disease (SD), as assessed by BICR/ investigator per RECIST 1.1 |
| Duration of Response (DoR) | Randomization up to approximately 24 months | DoR is defined as the time from the date of first documented CR or PR until date of documented disease progression per RECIST 1.1, as assessed by BICR/investigator or death due to any cause, whichever occurs first. |
| Time to Response (TTR) | Randomization up to approximately 24 months | TTR is defined as the time from the date of randomization until the first documentation of CR or PR as assessed by BICR/investigator per RECIST 1.1. |
| AEs and SAEs | AEs should be collected from signing the informed consent form (ICF) until 30 days after the last dose | Incidence and severity of AEs and SAEs (per CTCAE 5.0), and clinically significant abnormal laboratory findings |
| Mean change from baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) | Randomization up to approximately 24 months | To assess the impact of SKB264 on disease related symptoms and health related quality of life (HRQoL) in this patient population |
| Mean change from baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Breast Cancer Module 23 (EORTC QLQ-BR23) | Randomization up to approximately 24 months | To assess the impact of SKB264 on disease related symptoms and health related quality of life (HRQoL) in this patient population |
| Anti-drug Antibodies (ADA) for SKB264 | Day1 and Day15 of Cycle 1 (each cycle is 28 days), Day1 of Cycle 3, Cycle 6, and so on (every 3 cycles), up to approximately 24 months | Immunogenicity test results and titer values of SKB264 |
| Maximum observed plasma concentration (Cmax) of SKB264-ADC, SKB264-TAB and free KL610023 | Day1 and Day15 of Cycle 1 (each cycle is 28 days), Day1 of Cycle 3, Cycle 6, and so on (every 3 cycles), up to approximately 24 months | To assess the pharmacokinetic (PK) profile of SKB264. |
| Minimum observed plasma concentration (Cmin) of SKB264-ADC, SKB264-TAB and free KL610023 | Day1 and Day15 of Cycle 1 (each cycle is 28 days), Day1 of Cycle 3, Cycle 6, and so on (every 3 cycles), up to approximately 24 months | To assess the pharmacokinetic (PK) profile of SKB264. |
Countries
China
Contacts
CONTACTYina Diao
Outcome results
None listed