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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer Stage II; Breast Cancer Stage III; Triple -Negative Breast Cancer; Early Stage Triple-Negative Breast Carcinoma; Triple Negative Breast Cancer (TNBC), Early Setting
• Intervention / Treatment: Drug: Standard of care (capecitabine or olaparib); Drug: Standard of care plus pembrolizumab

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Robin van den Borg, MD; Phone Number: 1405 +31205129111; Email: planet@nki.nl
• Study Contact Backup: Name: Annemiek van Ommen-Nijhof, MD, PhD; Phone Number: +31205129111; Email: a.nijhof@nki.nl

Participation Criteria

Eligibility Criteria

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

Description

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

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
Active Comparator: Standard of care; Patients randomized to the control arm of the trial will receive standard of care adjuvant treatment (capecitabine or, in case of BRCA germline mutation, olaparib (if reimbursed)).	Drug: Standard of care (capecitabine or olaparib); Standard of care adjuvant treatment (capecitabine or olaparib); Other Names: Xeloda / Lynparza
Experimental: Standard of care plus pembrolizumab; Patients randomized to the investigational arm of the trial will receive standard of care adjuvant treatment (capecitabine or, in case of BRCA germline mutation, olaparib (if reimbursed)) plus pembrolizumab.	Drug: Standard of care plus pembrolizumab; Standard of care adjuvant treatment (capecitabine or olaparib) plus pembrolizumab; Other Names: KEYTRUDA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Invasive disease free survival (IDFS)	IDFS, defined as time since randomisation to local or distant breast cancer recurrence, second primary non-breast cancer or death due to any cause, whichever occurs first.	Up to 10 years after inclusion of the last patient

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Distant disease free survival (DDFS)	DDFS, defined as time from randomisation to distant recurrence or death due to any cause.	Up to 10 years after inclusion of the last patient
Overall survival (OS)	OS, defined as time from randomisation to death due to any cause.	Up to 10 years after inclusion of the last patient
Safety/adverse events of adjuvant pembrolizumab	Measured by adverse events (AEs), adverse events of special interest (AESIs) and serious adverse events (SAEs).	Up to 28 days after inclusion of the last patient
Health related quality of life (HRQoL) - EORTC Quality of Life Questionnaire (QLQ)-C30	The effect of adjuvant pembrolizumab on health-related quality of life (HRQoL), assessed via Quality of Life Questionnaire (QLQ)-C30. For functional and global HRQoL scales, higher scores represent a better level of functioning and are converted to a 0 to 100 scale. For symptom-oriented scales, a higher score represents more severe symptoms.	Up to 1 year after inclusion of the last patient
Health related quality of life (HRQoL) - EORTC Quality of Life Questionnaire (QLQ)-BR42	The effect of adjuvant pembrolizumab on health-related quality of life (HRQoL), assessed via Quality of Life Questionnaire (QLQ)-BR42. For functional and global HRQoL scales, higher scores represent a better level of functioning and are converted to a 0 to 100 scale. For symptom-oriented scales, a higher score represents more severe symptoms.	Up to 1 year after inclusion of the last patient
Health related quality of life (HRQoL) - EuroQol Health Utilities Index (EQ-5D)	The effect of adjuvant pembrolizumab on health-related quality of life (HRQoL), assessed via EuroQol Health Utilities Index (EQ-5D). Overall scores range from 0 to 1, with low scores representing a higher level of dysfunction and 1 as perfect health	Up to 1 year after inclusion of the last patient
Cost-utility measured per incremental cost-effectiveness ratio (ICER)	Cost-utility, based on the incremental cost-effectiveness ratio (ICER).	Up to 28 days after inclusion of the last patient
Efficacy of pembrolizumab according to tissue biomarkers	Efficacy of pembrolizumab according to tissue biomarkers (including but not limited to stromal tumor infiltrating lymphocytes (sTILs) and programmed death-ligand 1 (PD-L1 expression))	Up to 10 years after inclusion of the last patient

Collaborators and Investigators

• Sponsor: The Netherlands Cancer Institute
• Collaborators: BOOG Study Center; Stichting Treatmeds; Zorgevaluatie en Gepast Gebruik (ZE&GG); Integraal Kankercentrum Nederland (IKNL)
• Investigators: Principal Investigator: Gabe Sonke, MD, PhD, Netherlands Cancer Institute - Antoni van Leeuwenhoek; Principal Investigator: Marleen Kok, MD, PhD, Netherlands Cancer Institute - Antoni van Leeuwenhoek; Principal Investigator: Agnes Jager, MD, PhD, Erasmus MC Cancer Institute

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2032
• Study Completion (Estimated): April 1, 2036

Study Registration Dates

• First Submitted: December 17, 2025
• First Submitted That Met QC Criteria: March 17, 2026
• First Posted (Actual): March 20, 2026

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Breast cancer; Pembrolizumab; TNBC; Adjuvant; Triple negative breast cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Health Services Administration; Health Care Quality, Access, and Evaluation; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Quality of Health Care; Quality Indicators, Health Care; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Standard of Care; pembrolizumab; olaparib
• Other Study ID Numbers: M25PLN; 2025-524229-41-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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