Efficacy and Safety of PD-L1 Monoclonal Antibody Combined With Metronomic VEX in Advanced Triple-negative Breast Cancer

NCT06229067 | Not Yet Recruiting Phase 2

• 1 other identifier: NCC4279
• Study Type: interventional
• Target: 182
• Locations: 0 countries
• Sites: N/A

Brief Summary

In recent years, immune therapy has significantly altered the treatment landscape for various malignant tumors, including breast cancer. Apart from its direct cytotoxic effects on tumor cells, metronomic chemotherapy has the potential to modulate the immune microenvironment, thereby demonstrating substantial synergistic potential with immune therapy. In a previous prospective adaptive randomized phase II clinical trial, we identified a promising regimen involving PD-1 monoclonal antibody in combination with vinorelbine + cyclophosphamide + capecitabine (VEX) metronomic chemotherapy. Building on this foundation, we plan to conduct a multicenter, randomized, controlled phase II study to evaluate the efficacy and safety of the PD-L1 monoclonal antibody in combination with VEX metronomic chemotherapy for patients with advanced triple-negative breast cancer, aiming to provide crucial evidence to guide medication for patients in advanced stages. The control group will receive metronomic oral vinorelbine 20 mg every other day + cyclophosphamide 50 mg daily + capecitabine 500 mg three times daily. The experimental group will receive additional PD-L1 inhibitor adebrelimab at a dose of 1200 mg via intravenous infusion every three weeks. Each cycle consists of three weeks, with imaging examinations conducted every six weeks (two cycles) to assess treatment efficacy. Subjects will continue medication until imaging indicates disease progression, toxicity becomes intolerable, withdrawal of informed consent, or the investigator deems it necessary to terminate medication. Evaluation will include efficacy indicators such as median progression-free survival, safety indicators like drug-related adverse reactions, patient survival quality, along with an exploratory analysis of biomarkers potentially associated with efficacy.

Conditions

Breast Cancer; Triple Negative Breast Cancer

Keywords

PD-L1 inhibitor; immunotherapy; metronomic chemotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Measured from the date of study drugs start to the date of the first objective disease progression or death.

  24 months

Secondary Outcomes (5)

• Overall Survival

  24 months

• Disease Control Rate

  6 weeks of treatment

• Objective Response Rate

  6 weeks of treatment

• Duration of Response

  24 months

• Adverse Events

  24 months

Study Arms (2)

adebrelimab + VEX

EXPERIMENTAL

Adebrelimab at a dose of 1200 mg via intravenous infusion every three weeks, in combination with metronomic oral vinorelbine 20 mg every other day + cyclophosphamide 50 mg daily + capecitabine 500 mg three times daily

Drug: Adebrelimab; Drug: Vinorelbine; Drug: Cyclophosphamide (tablet); Drug: Capecitabine

VEX

ACTIVE COMPARATOR

Metronomic oral vinorelbine 20 mg every other day + cyclophosphamide 50 mg daily + capecitabine 500 mg three times daily

Drug: Vinorelbine; Drug: Cyclophosphamide (tablet); Drug: Capecitabine

Interventions

Adebrelimab DRUG

Adebrelimab at a dose of 1200 mg via intravenous infusion every three weeks. Adebrelimab will continue to be administered as long as patient experiences clinical benefit in the opinion of the investigator or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent.

adebrelimab + VEX

Vinorelbine DRUG

Metronomic oral vinorelbine 20 mg every other day. Vinorelbine will continue to be administered as long as patient experiences clinical benefit in the opinion of the investigator or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent.

VEX; adebrelimab + VEX

Cyclophosphamide (tablet) DRUG

Metronomic oral cyclophosphamide 50 mg daily. Cyclophosphamide will continue to be administered as long as patient experiences clinical benefit in the opinion of the investigator or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent.

VEX; adebrelimab + VEX

Capecitabine DRUG

Metronomic oral capecitabine 500 mg three times daily. Capecitabine will continue to be administered as long as patient experiences clinical benefit in the opinion of the investigator or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent.

VEX; adebrelimab + VEX

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female participants aged ≥18 years who have signed informed consent and have an expected survival of ≥3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status score ≤2 within 21 days prior to the first dose of medication.
• Participants with clear clinical records of metastatic triple-negative breast cancer, as specified in the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines.
• Participants with metastatic breast cancer who have received no more than first-line chemotherapy.
• Participants with at least one measurable lesion, as defined by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
• Participants with a history of receiving anthracycline and/or taxane-based treatments, including:
• Use of anthracyclines and/or taxanes during adjuvant or neoadjuvant therapy before breast cancer recurrence.
• Ineffectiveness observed during or after chemotherapy based on anthracyclines and/or taxanes.
• Participants deemed unsuitable for first-line treatment with anthracycline and/or taxane-based chemotherapy according to the investigator's judgment.
• Completion of radiotherapy before the first dose of study medication, with a minimum interval of 4 weeks since the end of radiotherapy.
• For participants with a history of surgery, a minimum interval of 30 days between surgery and the first dose of medication, with complete recovery from the surgical procedure.
• Normal bone marrow function, evidenced by:
• Absolute neutrophil count (ANC) ≥ 1500/mm².
• Platelets ≥ 100,000/mm².
• Hemoglobin (Hb) ≥ 10 g/dL.

You may not qualify if:

• Current or past history of malignancies other than breast cancer, excluding: cured non-melanoma skin cancer, cured cervical carcinoma in situ, or cured other primary solid tumors with no evidence of disease activity and no curative treatment within the last 3 years.
• Solely having pleural effusion, ascites, bone metastases, or other unmeasurable lesions.
• Malabsorption syndrome or diseases significantly affecting gastrointestinal function, prior gastrectomy, or resection of the proximal small intestine that may affect the absorption of oral chemotherapeutic agents.
• Swallowing difficulties or inability to swallow tablets.
• Symptomatic brain or leptomeningeal metastasis; suspected signs or symptoms of central nervous system (CNS) involvement should be excluded by CT or MRI scans.
• Other severe diseases or medical conditions discovered by the investigator during screening, including:
• Clinically significant heart diseases.
• Unstable diabetes.
• Uncontrolled hypercalcemia.
• Clinically significant active infections within the last 2 weeks.
• History of organ transplantation.
• Peripheral neuropathy of grade ≥2 according to NCI version 5.0.
• Concurrent use of any other antitumor therapy for metastatic breast cancer.
• Requirement for concurrent anticoagulant therapy.
• Status of pregnancy, lactation, or unwillingness to use effective contraception for at least one month during the entire study period and for at least one month after the last dose of the study drug.

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Vinorelbine; Cyclophosphamide; Tablets; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Dosage Forms; Pharmaceutical Preparations; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: January 19, 2024
• First Posted: January 29, 2024
• Study Start: January 19, 2024
• Primary Completion: January 19, 2025
• Study Completion (Estimated): January 19, 2027
• Last Updated: January 29, 2024

Record last verified: 2024-01