Evaluating the Efficacy and Safety of PD-L1 Monoclonal Antibody Combined with VEX Metronomic Chemotherapy and Concurrent or Delayed Radiotherapy in Patients with Advanced HER2-Negative Breast Cancer with Brain Metastasis

Chinese Academy of Medical Sciences & Peking Union Medical College

Status and phase: Not yet enrolling; Phase 2

Conditions: Brain Metastasis from Advanced HER2-negative Breast Cancer

Treatments: Drug: Adelumab+VEX Metronomic Chemotherapy+Delayed Radiotherapy; Drug: Adelumab+VEX Metronomic Chemotherapy+Concurrent Radiotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT06839560

NCC5108

Details and patient eligibility

About

A Prospective, multicenter, randomized controlled phase II study to evaluate the efficacy and safety of PD-L1 monoclonal antibody combined with vinorelbine + cyclophosphamide + capecitabine (VEX) metronomic chemotherapy and concurrent or delayed radiotherapy in patients with advanced HER2-negative breast cancer with brain metastasis

Enrollment: 102 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Males or females who are at least 18 years of age on the day of signing the informed consent form.

2. Patients with metastatic HER2-negative breast cancer brain metastasis, with clear clinical documentation; specific criteria refer to the guidelines of the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP).

3. Patients who have received no more than one line of chemotherapy during the metastatic stage of breast cancer.

4. Patients with brain metastasis should not require immediate local therapy during the trial and meet at least one of the following criteria:

   1. The patient has not previously received intracranial radiotherapy.
   2. The patient has not previously undergone surgery for intracranial metastases; if surgery was performed, the surgical lesion is not the target for the planned radiotherapy, or it is the target lesion and has recurred after surgery.

5. The patient must have at least one measurable intracranial lesion, with the longest diameter baseline accurately measurable by magnetic resonance imaging (MRI) as ≥10 mm and suitable for precise repeated measurement according to RECIST 1.1 in combination with RANO criteria. Measurable extracranial lesions are not required.

6. Patients with suspected or confirmed leptomeningeal metastasis should be excluded.

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, assessed within 10 days before the start of study treatment.

8. Patients may have previously received anthracycline (e.g., doxorubicin, epirubicin) and/or taxane (e.g., paclitaxel, docetaxel) therapy, specifically including:

   1. Before breast cancer recurrence, the patient received anthracycline and/or taxane during adjuvant or neoadjuvant treatment.
   2. The patient experienced treatment failure during or after anthracycline and/or taxane-based chemotherapy.
   3. In the judgment of the investigator, the patient is not suitable for anthracycline and/or taxane-based chemotherapy as a first-line treatment regimen.

9. Female patients are not pregnant, not breastfeeding, and agree to use necessary contraceptive measures.

10. The patient is able to sign the informed consent form to participate in the study.

11. The patient has adequate organ function, as detailed in Table 1 of the study protocol; all screening laboratory tests should be completed within 10 days before the start of study treatment.

Exclusion criteria

1. The subject has leptomeningeal metastasis.
2. If the patient has concurrent brain metastasis, the neurological symptoms are too severe to cooperate with radiotherapy.
3. Malabsorption syndrome, or the disease significantly affects gastrointestinal function; or after subtotal gastrectomy, or after proximal small bowel resection, which may affect the absorption of oral metronomic chemotherapy agents.
4. The subject has dysphagia or is unable to swallow tablets.
5. Known history of another invasive malignancy that is progressing or requires active treatment within the past 5 years. (Subjects with a history of cutaneous basal cell carcinoma, squamous cell carcinoma of the skin, ductal carcinoma in situ of the breast treated with curative intent, or in situ cervical cancer are not excluded.)
6. Previous treatment with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents, or targeted drugs acting on another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX40, CD137).
7. Diagnosis of immunodeficiency or receiving long-term systemic corticosteroid therapy (daily dose exceeding 10 mg prednisone equivalent) or any form of immunosuppressive therapy within 7 days before the first dose of study treatment.
8. Active autoimmune disease requiring systemic treatment within the past 2 years (e.g., use of disease-modifying drugs, corticosteroids, or immunosuppressive agents).
9. History of pneumonia requiring steroid treatment (non-infectious) or current pneumonia.
10. Positive urine pregnancy test within 72 hours before the first dose of study treatment.
11. Active infection requiring systemic treatment.
12. Known history of active tuberculosis.
13. Echocardiogram performed at screening confirms left ventricular ejection fraction (LVEF) <50% or below the institutional lower limit of normal.
14. Other significant cardiac disease, such as: myocardial infarction, acute coronary syndrome, or history of coronary artery angioplasty/stent placement/bypass surgery within the past 6 months; New York Heart Association (NYHA) Class II-IV congestive heart failure (CHF) or history of NYHA Class III or IV CHF.
15. Known history of human immunodeficiency virus (HIV) infection.
16. Known history of hepatitis B (defined as positive hepatitis B surface antigen [HBsAg]) or known active hepatitis C virus infection (defined as detectable HCV RNA [qualitative]).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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102 participants in 2 patient groups

Experimental Group (Concurrent Radiotherapy)

Experimental group

Description:

1. Adelumab: 1200 mg on Day 1, every 3 weeks (q3w). 2. VEX Metronomic Chemotherapy: 1) Vinorelbine: 20 mg orally, every other day, every 3 weeks (q3w). 2) Cyclophosphamide: 50 mg orally, once daily, every 3 weeks (q3w). 3) Capecitabine: 500 mg orally, three times daily, every 3 weeks (q3w). 3. Radiotherapy: The interval between radiotherapy and immunotherapy should be within 3 weeks, with no specific order required. Different radiotherapy techniques will be selected based on the size and location of the metastatic lesions: 1. Stereotactic Body Radiation Therapy (SBRT), 2. Spatially Fractionated Radiation Therapy (SFRT), 3. Low-dose Radiotherapy (LDRT).

Treatment:

Drug: Adelumab+VEX Metronomic Chemotherapy+Concurrent Radiotherapy

Control Group (Delayed Radiotherapy)

Active Comparator group

Description:

1. Adelumab: 1200 mg on Day 1, every 3 weeks (q3w). 2. VEX Metronomic Chemotherapy: 1) Vinorelbine: 20 mg orally, every other day, every 3 weeks (q3w). 2) Cyclophosphamide: 50 mg orally, once daily, every 3 weeks (q3w). Capecitabine: 500 mg orally, three times daily, every 3 weeks (q3w). 3. Radiotherapy: If there is intracranial disease progression but extracranial disease remains stable, the systemic treatment regimen of Adelumab + VEX metronomic chemotherapy will be continued, with the addition of intracranial radiotherapy. If there is intracranial disease progression and extracranial disease progression, the systemic treatment regimen will be modified, with the addition of intracranial radiotherapy. The radiotherapy positioning and techniques will be the same as those used in the experimental group.

Treatment:

Drug: Adelumab+VEX Metronomic Chemotherapy+Delayed Radiotherapy