A Study of SKB264 Versus Investigator's Choice of Chemotherapy in Subjects With Unresectable Locally Advanced, Relapsed, or Metastatic HR+/HER2- Breast Cancer Who Have Previously Failed Endocrine Therapy

Not Applicable

Not yet recruiting

• Conditions: Metastatic Breast Cancer
• Interventions: Drug: SKB264; Drug: Nab-paclitaxel; Drug: Paclitaxel; Drug: Capecitabine

• Registration Number: NCT07071337
• Lead Sponsor: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd.

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.

Study Timeline

• Status Verified: 2025-06
• Study First Submitted: 2025-06-19
• Study Start: 2025-07-01
• Study First Submitted QC: 2025-07-08
• Last Update Submitted: 2025-07-08
• Study First Posted: 2025-07-17
• Last Update Posted: 2025-07-17
• Primary Completion: 2027-07
• Study Completion: 2031-02-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 430

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 (Stage IIIc) 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. Central nervous system (CNS) metastases (including parenchymal brain metastases or metastases to meninges) or cancerous meningitis;
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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SKB264	SKB264	-
Investigator's Choice of Chemotherapy	Nab-paclitaxel	Nab-paclitaxel, paclitaxel or capecitabine will be administered and managed according to the investigator's clinical judgment, guided by clinical practice.
Investigator's Choice of Chemotherapy	Paclitaxel	Nab-paclitaxel, paclitaxel or capecitabine will be administered and managed according to the investigator's clinical judgment, guided by clinical practice.
Investigator's Choice of Chemotherapy	Capecitabine	Nab-paclitaxel, paclitaxel or capecitabine will be administered and managed according to the investigator's clinical judgment, guided by clinical practice.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.

Trial Locations

Locations (2)

The Fifth Medical Center of the Chinese PLA General Hospital; 🇨🇳 Beijing, Beijing, China

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China