SKB264 versus investigator's choice chemotherapy for unresectable or metastatic HR+/HER2- breast cancer

A Randomized, Open-label, Multicenter Phase III Clinical Study of SKB264 Versus Investigator's Choice of Chemotherapy in Subjects With Unresectable Locally Advanced, Relapsed, or Metastatic Hormone Receptor-positive (HR+)/Human Epidermal Growth Factor Receptor 2-negative (HER2-) Breast Cancer Who Have Previously Failed Endocrine Therapy

This will test whether SKB264 works better than commonly chosen chemotherapy for adults with unresectable or metastatic HR+/HER2- breast cancer who no longer benefit from hormone therapy.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 430 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. (industry)
• Drugs / interventions: chemotherapy, immunotherapy, Radiation
• Locations: 2 sites (Beijing, Beijing Municipality and 1 other locations)
• Trial ID: NCT07071337 on ClinicalTrials.gov

What this trial studies

This is a randomized, open-label, multicenter phase 3 trial comparing SKB264 monotherapy to investigator's choice chemotherapy (nab-paclitaxel, paclitaxel, or capecitabine) in patients with unresectable locally advanced, relapsed, or metastatic HR+/HER2- breast cancer after endocrine therapy failure. Participants must not have received systemic chemotherapy for their advanced disease (prior adjuvant/neoadjuvant chemotherapy is allowed if completed more than 6 months before enrollment) and must provide recent or archival tumor tissue. The trial will collect efficacy endpoints such as tumor response and progression-free survival along with safety and tolerability data. Sites are located at major cancer centers in China and the treatment assignment is open-label.

Who should consider this trial

Good fit: Adults aged 18–75 with histologically confirmed HR+/HER2- unresectable locally advanced, relapsed, or metastatic breast cancer who progressed on endocrine therapy and have not received systemic chemotherapy for advanced disease are ideal candidates.

Not a fit: Patients with HER2-positive tumors, those who have already had systemic chemotherapy for metastatic disease, or those who are not medically fit for chemotherapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, SKB264 could provide an effective new treatment option with improved tumor control or a different side-effect profile compared with standard chemotherapy.

How similar studies have performed: Other antibody–drug conjugates and targeted agents have shown benefit in metastatic breast cancer settings, but SKB264 itself has limited prior phase 3 evidence to confirm efficacy.

Eligibility criteria

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.

Where this trial is running

Beijing, Beijing Municipality and 1 other locations

• The Fifth Medical Center of the Chinese PLA General Hospital — Beijing, Beijing Municipality, China (RECRUITING)
• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Study coordinator: Yina Diao

Conditions: Metastatic Breast Cancer, SKB264, HR+/HER2- breast cancer