Posaconazole Plus PD-1 Inhibitors and Chemotherapy vs PD-1 Inhibitors and Chemotherapy in Neoadjuvant Therapy for Triple Negative Breast Cancer (PRISM-TNBC)

A Phase II, Randomised, Open-label, Multicentre Study of Posaconazole Plus PD-1 Inhibitors and Chemotherapy Versus PD-1 Inhibitors and Chemotherapy as Neoadjuvant Therapy for Triple Negative Breast Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Nab-paclitaxel; Drug: Anthracycline; Drug: Cyclophosphamide; Drug: Carboplatin; Drug: PD-1 inhibitors; Drug: Posaconazole

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 72 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 of Cycle 1 only: 300 mg bid; from Day 2, maintenance dose of 300 mg qd, oral administration. 21 days per treatment cycle, for a total of 8 cycles.). 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 Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Pengfei Qiu, MD; Phone Number: +86053167626215; Email: qiu.pf@outlook.com
• Study Contact Backup: Name: Zhiqiang Shi, MD; Phone Number: +86053167626215; Email: shizhiqiang1024@163.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250117
      • Recruiting
      • Breast Cancer Center Shandong Cancer Hospital and Institute Shandong First Medical University and Shandong Academy of Medical Sciences
      • Contact: Pengfei Qiu; Phone Number: +86053167626215; Email: qiu.pf@outlook.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Chemotherapy + PD-1 inhibitors; Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with PD-1 inhibitors	Drug: Nab-paclitaxel; Nab-paclitaxel 260mg/m2 d1 q21d; Drug: Anthracycline; Epirubicin 90-100mg/m2 d1 q21d or Doxorubicin 50-60mg/m2 d1 q21d; Drug: Cyclophosphamide; Cyclophosphamide 1000mg/m2 d1 q21d; Drug: Carboplatin; Carboplatin AUC=5-6 d1 q21d; Drug: PD-1 inhibitors; Toripalimab, Pembrolizumab and Camrelizumab, etc.
Experimental: Chemotherapy + PD-1 inhibitors+Posaconazole; Nab-paclitaxel + carboplatin 4 cycles, sequential anthracycline + cyclophosphamide 4 cycles in combination with PD-1 inhibitors and posaconazole	Drug: Nab-paclitaxel; Nab-paclitaxel 260mg/m2 d1 q21d; Drug: Anthracycline; Epirubicin 90-100mg/m2 d1 q21d or Doxorubicin 50-60mg/m2 d1 q21d; Drug: Cyclophosphamide; Cyclophosphamide 1000mg/m2 d1 q21d; Drug: Carboplatin; Carboplatin AUC=5-6 d1 q21d; Drug: PD-1 inhibitors; Toripalimab, Pembrolizumab and Camrelizumab, etc.; Drug: Posaconazole; Day 1 of Cycle 1 only: 300 mg bid; from Day 2, maintenance dose of 300 mg qd, oral administration. 21 days per treatment cycle, for a total of 8 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response	Expected 25% increase in pCR rate	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	24 weeks

Collaborators and Investigators

• Sponsor: Shandong Cancer Hospital and Institute

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: January 16, 2025
• First Submitted That Met QC Criteria: January 25, 2025
• First Posted (Actual): January 31, 2025

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 23, 2026
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Posaconazole; Neoadjuvant Therapy; Triple-Negative Breast Cancer; Pathological Complete Response
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Organic Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Coordination Complexes; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Naphthacenes; Aminoglycosides; Immune Checkpoint Inhibitors; Cyclophosphamide; Carboplatin; 130-nm albumin-bound paclitaxel; posaconazole; Anthracyclines
• Other Study ID Numbers: POS-PEM-Ⅱ-NEO-TNBC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No