Adjuvant Pembrolizumab Versus Capecitabine or Olaparib in Patients with Early-Stage Triple-Negative Breast Cancer with Residual Disease Following Neoadjuvant Therapy
- Trial ID
- 2025-524229-41-00
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the clinical benefit of adding pembrolizumab to standard adjuvant treatment, consisting of capecitabine or olaparib, in patients with triple negative breast cancer exhibiting residual disease following neoadjuvant chemotherapy and pembrolizumab. Secondary objectives include:
- Assessment of the efficacy of adjuvant pembrolizumab within specific subgroups based on residual cancer burden and BRCA germline status.
- Evaluation of the safety profile associated with adjuvant pembrolizumab.
- Measurement of the impact on health-related quality of life.
- Analysis of the cost-utility of the intervention.
- Establishment of a registry for patients with stage II-III triple negative breast cancer intended to receive neoadjuvant chemotherapy in combination with pembrolizumab.
Participants
The sponsor did not provide the total number of participants. The study population consists of male and female patients with triple negative breast cancer. Eligible individuals are aged 18 years or older and exhibit a World Health Organization performance status of 0-2. Participants must have had stage II or stage III disease prior to neoadjuvant chemotherapy and must have demonstrated non-pathologic complete response, defined by a residual cancer burden score greater than 0. The cohort includes those who completed neoadjuvant treatment with chemotherapy and pembrolizumab and underwent breast surgery within 12 weeks of inclusion. Requirements for enrollment include adequate organ function and the scheduled initiation of adjuvant treatment with capecitabine or olaparib.
Plans and Procedures
This multicenter, randomized, phase III, pragmatic clinical trial is designed to evaluate the efficacy of pembrolizumab as an addition to standard of care adjuvant treatment in patients with early-stage triple negative breast cancer presenting with residual disease following neoadjuvant chemotherapy and pembrolizumab. The study employs a low-intervention methodology to compare the test product against capecitabine or olaparib. The primary endpoint is invasive disease-free survival, with secondary endpoints including distant disease-free survival, overall survival, and safety assessments. The research process begins with a screening visit to assess eligibility based on residual tumor burden, tumor staging, and organ function. Following inclusion, participants undergo scheduled treatment and follow-up visits to monitor clinical outcomes and adverse events. The estimated total duration of the study period is ten years, from April 2026 to April 2036.
Treatment
The experimental treatment consists of pembrolizumab administered as a solution for infusion at a dosage of 400 mg via intravenous route.
Comparator treatments include capecitabine provided in film-coated tablet form at a dosage of 2500 mg/m2 through oral administration. Another comparator is olaparib, administered as 150 mg film-coated tablets orally. Additionally, a combination of tegafur, gimeracil, and oteracil is utilized in the form of hard capsules at a dosage of 60 mg/m2 via the oral route.
Efficacy
The primary efficacy endpoint is invasive disease-free survival (IDFS). Secondary endpoints include distant disease-free survival (DDFS), overall survival (OS), and cost-effectiveness. Assessment of safety through adverse events is also conducted. Furthermore, global health, quality of life, and physical functioning are evaluated.
The assessment of quality of life and physical functioning utilizes the following validated instruments:
- EQ-5D
- EORTC QLQ-C30
- EORTC QLQ-BR42
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male or female, ≥18 years of age on day of signing informed consent
- Stage II or III TNBC prior to the start of neoadjuvant treatment: a) Locally assessed stage II or III TNBC according to the primary tumor (T) and regional lymph node (N) staging as per the American Joint Committee on Cancer (AJCC) for breast cancer staging criteria version 8; b) Locally assessed estrogen receptor (ER) and/or progesterone receptor (PR) expression <10% and HER2-negative according to the ASCO-CAP guideline
- The patient has received neoadjuvant treatment with chemotherapy (containing at least anthracyclines and taxanes) and pembrolizumab, with a minimum of two 6-weekly (or four 3-weekly) cycles of pembrolizumab
- The patient underwent breast surgery ≤12 weeks prior to inclusion in the study
- The patient is scheduled to start standard of care adjuvant treatment with capecitabine or olaparib (pending reimbursement), based on non-pCR after neoadjuvant treatment, defined as RCB score >0
- World Health Organization (WHO) performance status 0-2
- Adequate organ function, as assessed ≤30 days prior to the screening: a) Absolute neutrophil count (ANC) ≥1,000/mm3 (1.0 x 10e9 /L); b) Platelets ≥50,000/mm3 (50 x 10e9 /L); c) Estimated creatinine clearance ≥ 30 mL/min as calculated using the method standard for the institution; d) Total serum bilirubin ≤1.5 x upper limit of normal (ULN) (≤3.0 x ULN if Gilbert’s disease); e) Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤3 x ULN
- Participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 6 months after the last dose of study medication
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
- Willingness to provide written informed consent, according to the Good Clinical Practice (GCP) and national/local regulations
Exclusion Criteria
- Contra-indications for any of the study drugs
- Other invasive malignancies, except when treated with curative intent without chemotherapy AND more than 5 years ago
- The presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 The Netherlands | Recruiting | 30 Apr 2026 | — |
| Netherlands | — | — | 1000 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Teysuno 15 mg/4.35 mg/11.8 mg hard capsules | Comparator | HARD CAPSULES | ORAL | 60 | 24 | PRD677321 |
Lynparza 150 mg film-coated tablets | Comparator | FILM-COATED TABLETS | ORAL | 600 | 52 | PRD6152626 |
Capecitabine Accord 500 mg film-coated tablets | Comparator | FILM-COATED TABLETS | ORAL | 2500 | 24 | PRD345306 |
KEYTRUDA 25 mg/mL concentrate for solution for infusion. | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS | 400 | 30 | PRD4323786 |
Capecitabine Accord 150 mg film-coated tablets | Comparator | FILM-COATED TABLETS | ORAL | 2500 | 24 | PRD345300 |