Posaconazole Plus Pembrolizumab and Chemotherapy Vs Pembrolizumab and Chemotherapy in Neoadjuvant Therapy for Triple Negative Breast Cancer

Phase 2

Recruiting

• Conditions: Breast Cancer
• Interventions: Drug: Nab-paclitaxel; Drug: Posaconazole; Drug: Carboplatin; Drug: Anthracycline; Drug: Cyclophosphamide; Drug: Pembrolizumab

• Registration Number: NCT06802757
• Lead Sponsor: Shandong Cancer Hospital and Institute

Brief Summary

Triple-negative breast cancer (TNBC) is as sociated with shorter overall survival than other breast cancer subtypes, despite the use of curative-intent anthracycline- and taxane-based systemic chemotherapy. Neoadjuvant therapy is now also recognized as the standard treatment for patients with high-risk TNBC. The Keynote-522 study demonstrated that the application of pembrolizumab has raised the pathological Complete Response (pCR) rate in TNBC to over 60%, but nearly 40% of patients still do not achieve pCR. How to further improve the pCR rate in TNBC patients has become a hot topic of current research.

Posaconazole is an antibiotic used to prevent invasive Aspergillus and Candida infections and to treat oropharyngeal candidiasis. Our preclinical studies have found that posaconazole can inhibit immune cell-mediated steroidogenesis to restrict TNBC tumor progression. The investigators design and begin a a prospective randomized controlled clinical study to explore the effectiveness of posaconazole in the neoadjuvant treatment of TNBC.

Detailed Description

OBJECTIVES: On the basis of chemotherapy combined with immunotherapy, posaconazole was used to further improve the pathological complete response (pCR) rate of high-risk triple-negative breast cancer (TNBC), and to explore biomarkers.

OUTLINE: From february 1st, 2025 to june 30th, 2026 the investigators will recruit 40 patients with first-time diagnosed early-stage TNBC. Enrolled patients were randomly divided into experimental group and control group on a 1:1 basis. Both groups received standard neoadjuvant chemotherapy combined with immunotherapy. The experimental group was treated with posaconazole (day 1: 300 mg po bid, from Day 2, start maintenance dose at 300 mg po qd, q21d). Standard surgical treatment was performed after 8 cycles and the surgical specimens were pathologically tested to compare the differences in pCR rates between the two groups.

Study Timeline

• Status Verified: 2025-01
• Study First Submitted: 2025-01-16
• Study First Submitted QC: 2025-01-25
• Study Start: 2025-02-01
• Last Update Submitted: 2025-02-01
• Study First Posted: 2025-03-25
• Last Update Posted: 2025-03-25
• Primary Completion: 2026-06-30
• Study Completion: 2028-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 20

Inclusion Criteria

1. Female, aged ≥ 18 and ≤ 70 years old;
2. first-confirmed TNBC;
3. cT1cN1-3M0 or cT2-4N0-3M0;
4. ECOG score 0-1 points.

Exclusion Criteria

1. Stage I or IV;
2. History of previous breast cancer;
3. Patients with a history of other tumors who have received systemic therapy or local radiotherapy;
4. No immune system disease or connective tissue disease;
5. No history of hormone therapy;
6. Pregnant/lactating.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Chemotherapy + PD-1 inhibitor	Nab-paclitaxel	Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with pembrolizumab
Chemotherapy + PD-1 inhibitor	Carboplatin	Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with pembrolizumab
Chemotherapy + PD-1 inhibitor	Anthracycline	Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with pembrolizumab
Chemotherapy + PD-1 inhibitor	Cyclophosphamide	Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with pembrolizumab
Chemotherapy + PD-1 inhibitor	Pembrolizumab	Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with pembrolizumab
Chemotherapy + PD-1 inhibitor+Posaconazole	Posaconazole	Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with pembrolizumab and posaconazole
Chemotherapy + PD-1 inhibitor+Posaconazole	Nab-paclitaxel	Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with pembrolizumab and posaconazole
Chemotherapy + PD-1 inhibitor+Posaconazole	Carboplatin	Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with pembrolizumab and posaconazole
Chemotherapy + PD-1 inhibitor+Posaconazole	Anthracycline	Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with pembrolizumab and posaconazole
Chemotherapy + PD-1 inhibitor+Posaconazole	Cyclophosphamide	Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with pembrolizumab and posaconazole
Chemotherapy + PD-1 inhibitor+Posaconazole	Pembrolizumab	Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with pembrolizumab and posaconazole

Primary Outcome Measures

Name	Time	Method
Pathological Complete Response	24 weeks	Expected 10% increase in pCR rate

Secondary Outcome Measures

Name	Time	Method
Breast pathological complete response	24 weeks
Objective response rate	24 weeks
3-year event-free survival rate	After a median follow-up of 3 years
Survival rate	After a median follow-up of 3 years
Security	24 weeks	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Trial Locations

Locations (1)

Breast Cancer Center Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences; 🇨🇳 Jinan, Shandong, China