## Protocol Section
### Identification Module
**NCT ID:** NCT06433609

**Brief Title:** 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

#### Organization Study ID Info
**ID:** BJGBYY-IIT-LCYJ-2024-008
#### Organization
**Class:** OTHER
**Full Name:** Beijing GoBroad Hospital
#### Secondary ID Infos
**Domain:** Jiangsu Hengrui Pharmaceuticals Co., Ltd.
**ID:** BC-MUL-IIT-ADC-SHR1316
**Type:** OTHER
### Status Module
#### Completion Date
**Date:** 2027-11

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-30

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-28

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2027-07

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-06

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-30
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-23
**Study First Submit QC Date:** 2024-05-28
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Beijing GoBroad Hospital

#### Responsible Party

**Investigator Affiliation:** Beijing GoBroad Hospital

**Investigator Full Name:** Yang Ke

**Investigator Title:** Associate chief physician

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Advanced Breast Cancer

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 131

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Drug: SHR-A1811

- Drug: Adebrelimab

**Label:** SHR-A1811+adebrelimab

**Type:** EXPERIMENTAL

#### Arm Group 2

**Intervention Names:**

- Drug: SHR-A1921

- Drug: Adebrelimab

**Label:** SHR-A1921+adebrelimab

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- SHR-A1811+adebrelimab

**Description:** Via intravenous infusion

**Name:** SHR-A1811

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- SHR-A1921+adebrelimab

**Description:** Via intravenous infusion

**Name:** SHR-A1921

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- SHR-A1811+adebrelimab

- SHR-A1921+adebrelimab

**Description:** Via intravenous infusion

**Name:** Adebrelimab

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 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.

**Measure:** 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 Outcomes

**Description:** 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.

**Measure:** 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

**Description:** 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.

**Measure:** 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

**Description:** 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.

**Measure:** DoR (duration of response)

**Time Frame:** up to 3.5 years

**Description:** 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).

**Measure:** 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

**Description:** OS is the time from the date of first dose until the date of death by any cause.

**Measure:** OS (overall survival)

**Time Frame:** up to 3.5 years

**Description:** 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.

**Measure:** Safety as assessed by percentage of patients with any Adverse Event (AE)

**Time Frame:** up to 3.5 years

### Eligibility Module

**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.

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** FEMALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** key3@gobroadhealthcare.com

**Name:** Yang Ke

**Phone:** +86-13592618724

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Beijing

**Contacts:**

***Contact 1:***

- **Email:** key3@gobroadhealthcare.com

- **Name:** Yang Ke

- **Phone:** +86-13592618724

- **Role:** CONTACT

***Contact 2:***

- **Name:** Yang Ke

- **Role:** PRINCIPAL_INVESTIGATOR

**Country:** China

**Facility:** Beijing GoBroad Hospital

**State:** Beijing

**Zip:** 102200

#### Overall Officials

**Official 1:**

**Affiliation:** Beijing GoBroad Hospital

**Name:** Yang Ke

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000001941

- Term: Breast Diseases

- ID: D000012871

- Term: Skin Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M5220

- Name: Breast Neoplasms

- Relevance: HIGH

- As Found: Breast Cancer

- ID: M5218

- Name: Breast Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15674

- Name: Skin Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000001943

- Term: Breast Neoplasms

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M4225

- Name: Antibodies

- Relevance: LOW

- As Found: Unknown

- ID: M10184

- Name: Immunoglobulins

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
