## Protocol Section
### Identification Module
**NCT ID:** NCT06418594

**Brief Title:** Adebrelimab Plus Apatinib and Etoposide for the Treatment of HER2-Negative Breast Cancer Brain Metastasis

**Official Title:** Adebrelimab Plus Apatinib and Etoposide for the Treatment of HER2-Negative Breast Cancer Brain Metastasis: A Phase II Study

#### Organization Study ID Info
**ID:** MA-BC-II-070
#### Organization
**Class:** OTHER
**Full Name:** Beijing 302 Hospital
### Status Module
#### Completion Date
**Date:** 2026-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-17

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-15

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-11-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-15

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-17
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-13
**Study First Submit QC Date:** 2024-05-15
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Beijing 302 Hospital

#### Responsible Party

**Investigator Affiliation:** Beijing 302 Hospital

**Investigator Full Name:** Wang Tao

**Investigator Title:** Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** Some studies have shown that approximately 15% of patients with advanced hormone receptor (HR) positive breast cancer and 1/3 of triple negative breast cancer will develop brain metastasis. At present, there is no unified drug treatment standard for HER2-negative breast cancer brain metastasis (BCBM). The evidence of single traditional chemotherapy drug as the main treatment of brain metastasis is not sufficient. Some exploratory studies on HER2-negative BCBM have shown that the central nervous system objective response rate (CNS-ORR) of anti-angiogenic drugs combined with chemotherapy is around 55%-80%。 Adebrelimab (a humanized PD-L1 monoclonal antibody) specifically blocks the binding of PD-1 and PD-L1, terminates the immunosuppressive signal produced by T cells, and makes T cells re-recognize tumor cells and kill them, thereby inhibiting tumor growth. In China, Adebelizumab has been approved for using in combination with chemotherapy as a first-line treatment for extensive stage small cell lung cancer. Apatinib (a small molecule VEGFR tyrosine kinase inhibitor) mainly plays an anti-angiogenic effect in the treatment of malignant tumors by inhibiting VEGFR. Apatinib has been approved monotherapy for advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma that has progressed or relapsed after at least two systematic chemotherapies, advanced liver cancer that has failed or is intolerable after at least first-line systematic treatment, and first-line treatment in patients with unresectable or metastatic hepatocellular carcinoma combined with camrelizumab.

Due to the lack of effective drug therapy for HER2-negative BCBM, a variety of treatment combinations are still being explored. We hypothesized that adebrelimab plus apatinib and etoposide is an explorable and effective treatment for HER2- negative BCBM.

### Conditions Module

**Conditions:**

- HER2-negative Breast Cancer Brain Metastases

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

**Intervention Model Description:** This study adopts a single-arm, open-label design, planning to enroll 30 patients with HER2-negative breast cancer brain metastasis.

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 30

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Adebrelimab: 1200mg， ivgtt，administered on the first day of each cycle, with a cycle of 21 days.

Apatinib: 250 mg, oral, once daily, continuous use, with a cycle of 21 days.

Etoposide: 50mg/day, oral, administered on days 1-14 of each cycle, with a cycle of 21 days.

**Intervention Names:**

- Drug: Adebrelimab

- Drug: Apatinib

- Drug: Etoposide

**Label:** Adebrelimab+Apatinib+Etoposide

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Adebrelimab+Apatinib+Etoposide

**Description:** Adebrelimab: 1200mg, ivgtt, administered on the first day of each cycle, with a cycle of 21 days

**Name:** Adebrelimab

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Adebrelimab+Apatinib+Etoposide

**Description:** Apatinib: 250 mg, oral, once daily, continuous use, with a cycle of 21 days

**Name:** Apatinib

**Other Names:**

- Apatinib Mesylate Tablets

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Adebrelimab+Apatinib+Etoposide

**Description:** Etoposide: 50mg/day, oral, administered on days 1-14 of each cycle, with a cycle of 21 days

**Name:** Etoposide

**Other Names:**

- VP-16

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Central nervous system objective response rate (CNS-ORR), as assessed according to the RANO-BM criteria

**Measure:** CNS-ORR

**Time Frame:** 2 months

#### Secondary Outcomes

**Description:** CNS progression-free survival

**Measure:** CNS-PFS

**Time Frame:** 1 Year

**Description:** According to recist1.1 standard, the proportion of patients whose extracranial best remission was CR or PR accounted for the total number of evaluable patients

**Measure:** Extracranial objective response rate

**Time Frame:** 2 Years

**Description:** The time to the date of first documented progression or date of death from any cause, whichever came first

**Measure:** Extracranial progression-free survival

**Time Frame:** 2 Years

**Description:** The time from the beginning of treatment to the time of death caused by any cause

**Measure:** OS

**Time Frame:** 3 Years

**Description:** Clinical benefit rate: CR+PR+SD≥6 months

**Measure:** CBR

**Time Frame:** 2 Years

**Description:** The time from the beginning of CR or PR to the time when the tumor was first evaluated as PD or any cause of death.

**Measure:** DoR

**Time Frame:** 2 Years

**Description:** Adverse events (AE), serious adverse events (SAE), and immune-related adverse events (irAE), in accordance with the NCI-CTC AE version 5.0 criteria. AE recorded from infromed consent to 28 days after treatment completion.

**Measure:** Safety

**Time Frame:** AE recorded from infromed consent to 28 days after treatment completion

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Female, aged ≥18 years
* Expected survival time ≥3 months.
* Histologically or cytologically confirmed HER2-negative (IHC 0 or 1+; or IHC 2+ ISH negative) locally recurrent or metastatic disease
* New brain metastasis or brain metastasis progression after treatment
* HR+ advanced breast cancer with prior CDK4/6 inhibitor treatment failure or the investigator deems unsuitable for CDK4/6 inhibitors
* At least one intracranial measurable lesion as defined by RECIST V1.1 criteria；
* ECOG PS 0-2；
* Patients must have the ability to swallow oral medication；
* Prior WBRT, stereotactic radiosurgery, and surgical resection are allowed；
* Organ function levels are basically normal, and the investigator believes that the study drug can be applied：
* Voluntarily join this study, sign the informed consent, have good compliance, and are willing to cooperate with follow-up

Exclusion Criteria:

* Urgent need for local treatment of brain metastasis
* Immunohistochemistry HER2 positive (IHC 3 or IHC 2 ISH amplification)
* Previously treated with Apatinib, Avelumab, or VP-16；
* Severe dysfunction of important organs such as the heart, liver, or kidneys；
* Inability to swallow, chronic diarrhea, and intestinal obstruction, with multiple factors affecting drug administration and absorption；
* Participants diagnosed with any other malignant tumor within 5 years before this study, excluding non-melanoma skin cancer that has undergone radical treatment. Basal cell or squamous cell skin cancer or cervical carcinoma in situ and thyroid papillary carcinoma。
* Patients who allergy to any component of the drugs in this protocol; patients with history of immunodeficiency, including HIV positive, HCV, active hepatitis B, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation
* History of any cardiac disease, including: (1) arrhythmia requiring medication or clinically significant; (2) myocardial infarction; (3) heart failure; (4) any other cardiac disease judged by the investigator to be unsuitable for participation in this trial, etc.
* Pregnant or lactation female patients; females of childbearing age with a positive baseline pregnancy test or unwilling to take effective contraceptive measures during the entire trial period；
* According to the investigator's judgment, there are severe accompanying diseases that endanger the patient's safety or affect the completion of the study (including but not limited to uncontrolled severe hypertension, severe diabetes, active infection, etc.).

**Minimum Age:** 18 Years

**Sex:** FEMALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** jinzhu2714@sina.com

**Name:** Jinmei Zhou, Doctor

**Phone:** +86-010-66947250

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Beijing

**Country:** China

**Facility:** The Fifth Medical Center of PLA General Hospital

**State:** Beijing

**Zip:** 100071

## 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

- ID: D000009385

- Term: Neoplastic Processes

- ID: D000010335

- Term: Pathologic Processes

- ID: D000016543

- Term: Central Nervous System Neoplasms

- ID: D000009423

- Term: Nervous System Neoplasms

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: BC10

- Name: Nervous System Diseases

### Condition Browse Module - Browse Leaves

- ID: M5220

- Name: Breast Neoplasms

- Relevance: HIGH

- As Found: Breast Cancer

- ID: M12307

- Name: Neoplasm Metastasis

- Relevance: HIGH

- As Found: Metastases

- ID: M5209

- Name: Brain Neoplasms

- Relevance: HIGH

- As Found: Brain Metastases

- ID: M5218

- Name: Breast Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15674

- Name: Skin Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12330

- Name: Neoplastic Processes

- Relevance: LOW

- As Found: Unknown

- ID: M18937

- Name: Central Nervous System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M12367

- Name: Nervous System Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000001943

- Term: Breast Neoplasms

- ID: D000009362

- Term: Neoplasm Metastasis

- ID: D000001932

- Term: Brain Neoplasms

### Intervention Browse Module - Ancestors

- ID: D000000972

- Term: Antineoplastic Agents, Phytogenic

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000059005

- Term: Topoisomerase II Inhibitors

- ID: D000059003

- Term: Topoisomerase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000047428

- Term: Protein Kinase Inhibitors

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M8191

- Name: Etoposide

- Relevance: HIGH

- As Found: Tolerability

- ID: M288166

- Name: Apatinib

- Relevance: HIGH

- As Found: Immunogenicity

- ID: M341643

- Name: Etoposide phosphate

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M25820

- Name: Protein Kinase Inhibitors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000005047

- Term: Etoposide

- ID: C000553458

- Term: Apatinib

### Misc Info Module

- Version Holder: 2024-05-31
