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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Breast Cancer
• Intervention / Treatment: Drug: SHR-A1811; Drug: Adebrelimab; Drug: SHR-A1921

• Study Type: Interventional
• Enrollment (Estimated): 131
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yang Ke; Phone Number: +86-13592618724; Email: key3@gobroadhealthcare.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 102200
      • Beijing GoBroad Hospital
      • Contact: Yang Ke; Phone Number: +86-13592618724; Email: key3@gobroadhealthcare.com
      • Principal Investigator: Yang Ke

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR-A1811+adebrelimab	Drug: SHR-A1811; Via intravenous infusion; Drug: Adebrelimab; Via intravenous infusion
Experimental: SHR-A1921+adebrelimab	Drug: Adebrelimab; Via intravenous infusion; Drug: SHR-A1921; Via intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR (objective response rate) by investigator	ORR is the percentage of evaluable patients with a confirmed investigator-assessed response of CR (complete response) or PR (partial response) per RECIST v1.1.	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

Outcome Measure	Measure Description	Time Frame
DCR (disease control rate) by investigator	DCR is the percentage of evaluable patients with a confirmed investigator-assessed response of CR (complete response), PR (partial response) or SD (stable disease) per RECIST v1.1.	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	CBR is the percentage of evaluable patients with a confirmed investigator-assessed response of CR (complete response), PR (partial response) or SD lasting≥24 weeks (stable disease) per RECIST v1.1.	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)	DoR is the time from the date of first detection of objective response (which is subsequently confirmed) until the date of objective radiographic disease progression.	up to 3.5 years
PFS (progression-free survival)	PFS is the time from the date of first dose until the date of objective radiographic disease progression or death (by any cause in the absence of progression).	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)	OS is the time from the date of first dose until the date of death by any cause.	up to 3.5 years
Safety as assessed by percentage of patients with any Adverse Event (AE)	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. Percentage of participants who experienced an adverse event and discontinued study drug due to an AE.	up to 3.5 years

Collaborators and Investigators

• Sponsor: Beijing GoBroad Hospital
• Investigators: Principal Investigator: Yang Ke, Beijing GoBroad Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: May 23, 2024
• First Submitted That Met QC Criteria: May 28, 2024
• First Posted (Actual): May 30, 2024

Study Record Updates

• Last Update Posted (Actual): May 30, 2024
• Last Update Submitted That Met QC Criteria: May 28, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: BJGBYY-IIT-LCYJ-2024-008; BC-MUL-IIT-ADC-SHR1316 (Other Identifier: Jiangsu Hengrui Pharmaceuticals Co., Ltd.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No