Clinical trial NCT06433609: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Advanced Breast Cancer
Lead sponsor: Beijing GoBroad Hospital
Sponsor class: OTHER
First posted: 2024-05-30
Enrollment: 131
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

1. 18 years to 75 years old (including boundary values), female patients with breast cancer;
2. ECOG PS Score: 0\~1;
3. Histologically or cytologically confirmed HER2-negative advanced breast cancer;
4. Disease progression after prior 1-2 lines of systemic therapy; if HR-positive, prior CDK4/6 inhibitor is necessary;
5. Based on RECIST v1.1, at least one measurable lesion;
6. Brain metastasis with no clinical symptoms, or treated, stable brain metastases are eligible;
7. No prior PD-(L)1 inhibitor;
8. Patients must have a life expectancy ≥ 6 months;
9. Adequate organ function and marrow function (no corrective treatment within 14 days before first dose);
10. Patients 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;
11. Available blood samples for ctDNA detection in the exploratory study;
12. Willing and able to provide written informed consent and comply with the requirements and restrictions in the protocol.

Exclusion Criteria:

1. Has known active brain metastasis which needs local therapy immediately;
2. Prior anti-HER2 or anti-TROP-2 treatment;
3. Has received or been receiving PD-(L)1 inhibitors and/or ADC containing a topoisomerase inhibitor-like payload;
4. Existence of third space fluid that is not well controlled by effective methods, e.g. drainage;
5. 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;
6. Use of other antitumor systemic treatment during the study;
7. Has active autoimmune disease or a history of autoimmune disease;
8. Known history of immunodeficiency, including HIV-positive, other acquired or innate immunodeficient disease, or known history of organ transplantation;
9. 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;
10. 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);
11. 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;
12. 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;
13. Hypersensitivity to study therapy or any of its excipients;
14. Has known clinically significant lung disease, including but not limited to: interstitial lung disease, pneumonitis, pulmonary fibrosis;
15. Known history of uncontrolled cardiovascular clinical symptom or disease that is not well controlled;
16. 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;
17. Patients 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;
18. Other conditions that might influence the study and analysis of results in the opinion of the investigator.

Primary outcomes:
measure: ORR (objective response rate) by investigator
timeFrame: 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 outcomes:
measure: DCR (disease control rate) by investigator
timeFrame: 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
measure: CBR (clinical benefit rate) by investigator
timeFrame: 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
measure: DoR (duration of response)
timeFrame: up to 3.5 years
measure: PFS (progression-free survival)
timeFrame: 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
measure: OS (overall survival)
timeFrame: up to 3.5 years
measure: Safety as assessed by percentage of patients with any Adverse Event (AE)
timeFrame: up to 3.5 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing GoBroad Hospital
state: Beijing
Study officials:
affiliation: Beijing GoBroad Hospital
name: Yang Ke
role: PRINCIPAL_INVESTIGATOR
References: