Posaconazole Plus Pembrolizumab and Chemotherapy vs Pembrolizumab and Chemotherapy in Neoadjuvant Therapy for Triple Negative Breast Cancer (PRISM-TNBC)

Shandong First Medical University

Status and phase: Enrolling; Phase 2

Conditions: Breast Cancer

Treatments: Drug: Carboplatin; Drug: Pembrolizumab; Drug: Cyclophosphamide; Drug: Nab-paclitaxel; Drug: Posaconazole; Drug: Anthracycline

Study type: Interventional

Funder types: Other

Identifiers

NCT06802757

POS-PEM-Ⅱ-NEO-TNBC

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 estimated patients

Sex: Female

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

Chemotherapy + PD-1 inhibitor

Other group

Description:

Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with pembrolizumab

Treatment:

Drug: Anthracycline

Drug: Pembrolizumab

Drug: Cyclophosphamide

Drug: Nab-paclitaxel

Drug: Carboplatin

Chemotherapy + PD-1 inhibitor+Posaconazole

Experimental group

Description:

Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with pembrolizumab and posaconazole

Treatment:

Drug: Anthracycline

Drug: Posaconazole

Drug: Pembrolizumab

Drug: Cyclophosphamide

Drug: Nab-paclitaxel

Drug: Carboplatin