Study of ADCs Combined With Adebrelimab in HER2-negative Advanced Breast Cancer

Official title

A Phase II Study of Antibody-Drug Conjugates (ADCs) Combined With Adebrelimab in HER2-negative Advanced Breast Cancer

Overview

Our study is aimed to evaluate the efficacy and safety of novel ADCs named SHR-A1811, SHR-A1921 and SHR-A2102 combined with adebrelimab in HER2-negative advanced breast cancer.

Interventions

• Drug SHR-A1811
  Via intravenous infusion
• Drug SHR-A1921
  Via intravenous infusion
• Drug Adebrelimab
  Via intravenous infusion
• Drug SHR-A2102
  Via intravenous infusion

Primary outcome measures

• ORR (objective response rate) by investigator [Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3.5 years]

Secondary outcome measures (6)

• DCR (disease control rate) by investigator [Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3.5 years]
• CBR (clinical benefit rate) by investigator [Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3.5 years]
• DoR (duration of response) [Time frame: up to 3.5 years]
• PFS (progression-free survival) [Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3.5 years]
• OS (overall survival) [Time frame: up to 3.5 years]
• Safety as assessed by percentage of patients with any Adverse Event (AE) [Time frame: up to 3.5 years]

Eligibility criteria

Inclusion criteria

• 18 years to 75 years old (including boundary values);
• ECOG PS Score: 0\~1;
• Histologically or cytologically confirmed HER2-negative advanced breast cancer;
• Disease progression after prior ≥1 line of systemic therapy; if HR-positive, prior CDK4/6 inhibitor is necessary;
• Based on RECIST v1.1, at least one measurable lesion;
• Brain metastasis with no clinical symptoms, or treated, stable brain metastases are eligible;
• Patients must have a life expectancy ≥ 6 months;
• Adequate organ function and marrow function (no corrective treatment within 14 days before first dose);
• Women of childbearing potential should have a negative urine or serum pregnancy, and must promise to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study therapy or be celibate; Men who are not surgically sterile (including those sterilized by methods other than bilateral orchiectomy \[e.g., vasectomy\]) and who intend to have sexual intercourse with female partners of childbearing potential must use a contraceptive method from enrollment, throughout the study, and for 6 months after the end of the study to prevent partner pregnancy;
• Available blood samples for ctDNA detection in the exploratory study;
• Willing and able to provide written informed consent and comply with the requirements and restrictions in the protocol.

Exclusion criteria

• Has known active brain metastasis which needs local therapy immediately;
• Prior use of ADCs with the same target as study drugs;
• Existence of third space fluid that is not well controlled by effective methods, e.g. drainage;
• Has received antitumor surgery, radiotherapy, chemotherapy, targeted therapy or immunological therapy within 4 weeks before first dose of study therapy; has received antitumor endocrine therapy within one week before first dose of study therapy;
• Use of other antitumor systemic treatment during the study;
• Has active autoimmune disease or a history of autoimmune disease;
• Known history of immunodeficiency, including HIV-positive, other acquired or innate immunodeficient disease, or known history of organ transplantation;
• Has active hepatitis B (HBsAg-positive and HBV DNA≥500 IU/mL), hepatitis C (positive for HCV antibody and HCV RNA above ULN) and hepatic cirrhosis;
• Has an active infection requiring antibiotics, antiviral or antifungal treatment, or pyrexia >38.5℃ of unknown origin during the screening period before first dose of study therapy (patients with pyrexia due to cancer could be enrolled determined by investigator);
• Receiving immunosuppressive medication, or systemic corticosteroid therapy for the purpose of immunosuppression (prednisone at >10mg/d or equivalent dose of other corticosteroids), and continuous use within 2 weeks before the first dose of study therapy;
• Other malignancy within prior 5 years unless curatively treated with no evidence of disease for at least recent 3 years, except: curatively treated in situ cancer of the cervix, skin basal cell carcinoma or skin squamous cell carcinoma;
• Hypersensitivity to study therapy or any of its excipients;
• Has known clinically significant lung disease, including but not limited to: interstitial lung disease, pneumonitis, pulmonary fibrosis;
• Known history of uncontrolled cardiovascular clinical symptom or disease that is not well controlled;
• Has received a live vaccine within 4 weeks before first dose of study therapy, or potential to receive a live vaccine during the trial treatment;
• Women with a positive serum or urine pregnancy test or who are breastfeeding; patients of childbearing potential who are unwilling or not available to use an effective method of contraception;
• Other conditions that might influence the study and analysis of results in the opinion of the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing GoBroad Hospital — Beijing

Identifiers

NCT: NCT06433609 · BJGBYY-IIT-LCYJ-2024-008 · BC-MUL-IIT-ADC-SHR1316

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗