Pembrolizumab Adjuvant in Patients With Early-stage Triple Negative Breast Cancer With Residual Disease After Neoadjuvant Pembrolizumab Plus Chemotherapy

PembroLizumab Adjuvant in Patients With Early-stage Triple NEgaTive Breast Cancer With Residual Disease After Neoadjuvant Pembrolizumab Plus Chemotherapy - the Multicenter, Randomized Phase III, Pragmatic PLANET Trial

The phase III, multicenter, pragmatic PLANET trial aims to evaluate the benefit and safety of pembrolizumab as an addition to standard of care adjuvant treatment (capecitabine or olaparib) in triple negative breast cancer (TNBC) patients with residual disease (non-pCR) after neoadjuvant chemotherapy and pembrolizumab. All study procedures resemble routine clinical practice as much as possible (i.e., pragmatic clinical trial). In addition to the randomized trial, a registry will be set up, in which patients who reach pCR (and therefore, do not receive adjuvant treatment) will be registered and followed.

Inclusion Criteria:

1. Male or female, ≥18 years of age on day of signing informed consent

2. Stage II or III TNBC prior to the start of neoadjuvant treatment

   1. 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
   2. Locally assessed estrogen receptor (ER) and/or progesterone receptor (PR) expression <10% and HER2-negative according to the ASCO-CAP guideline1

3. 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

4. The patient underwent breast surgery ≤12 weeks prior to inclusion in the study

5. 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 >02

6. World Health Organization (WHO) performance status 0-2

7. Adequate organ function, as assessed ≤30 days prior to the screening:

   1. Absolute neutrophil count (ANC) ≥1,000/mm3 (1.0 x 10e9 /L)
   2. Platelets ≥50,000/mm3 (50 x 10e9 /L);
   3. Estimated creatinine clearance ≥ 30 mL/min as calculated using the method standard for the institution;
   4. Total serum bilirubin ≤1.5 x upper limit of normal (ULN) (≤3.0 x ULN if Gilbert's disease);
   5. Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤3 x ULN

8. 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

9. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

10. Willingness to provide written informed consent, according to the Good Clinical Practice (GCP) and national/local regulations

Exclusion Criteria:

1. Contra-indications for any of the study drugs
2. Other invasive malignancies, except when treated with curative intent without chemotherapy AND more than 5 years ago
3. The presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
4. 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