Personalizing the use of pembrolizumab for patients who have a strong response in early triple negative breast cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Unicancer

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Jul 2025 → ongoing

Decision date (initial)

2025-03-20

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

PHRC, KCE Trials, RTF et RTFCCR

External identifiers

EU CT number

2024-515787-31-00

ClinicalTrials.gov

NCT06606730

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To determine the non-inferiority of observation as compared to 6 months of adjuvant pembrolizumab after surgery in terms of recurrence-free survival (RFS) in patients who experienced pCR after neoadjuvant chemotherapy and pembrolizumab.

Secondary objectives 16

1. Safety and Tolerability : To evaluate the incidence of Grade ≥ 2 AEs particularly immune related AEs (irAEs) in patients undergoing observation as compared to those treated with 6 months of adjuvant pembrolizumab after surgery
2. Safety and Tolerability : To evaluate change of PRO-CTCAE composite score of selected events (i.e., bloating, diarrhea, abdominal pain, rash, itching, anorexia, nausea, fatigue, dyspnea, radiation skin reaction , myalgia, arthralgia, pain, and peripheral sensory neuropathy) in patients undergoing observation as compared to those treated with 6 months of adjuvant pembrolizumab after surgery
3. Health-related quality of life and emotional distress : To evaluate the impact of 6 months of adjuvant pembrolizumab on overall quality of life (QoL) when compared with observation
4. Health-related quality of life and emotional distress : To describe trajectories of QoL over time in patients undergoing observation as compared to those treated with 6 months of adjuvant pembrolizumab after surgery
5. Health-related quality of life and emotional distress : To evaluate the impact of 6 months of adjuvant pembrolizumab overall on other QoL domains, including fatigue, emotional distress, pain, and sleep quality, as measured by the EORTC QLQ-C30, EORTC-BR42 and EQ5D5L
6. Health-related quality of life and emotional distress : To compare fear of cancer recurrence (FCR) in patients undergoing observation as compared to those treated with 6 months of adjuvant pembrolizumab after surgery
7. Fertility: To compare the rate of menstruation recovery in patients undergoing observation as compared to those treated with 6 months of adjuvant pembrolizumab after surgery
8. Fertility: To compare the rate of pregnancy in patients undergoing observation as compared to those treated with 6 months of adjuvant pembrolizumab after surgery
9. Fertility: To describe the patterns of LHRH agonist prescription
10. Efficacy : To assess invasive breast cancer-free survival (IBCFS) in patients undergoing observation as compared to those treated with 6 months of adjuvant pembrolizumab after surgery
11. Efficacy: To assess distant relapse-free survival (DRFS) in patients undergoing observation as compared to those treated with 6 months of adjuvant pembrolizumab after surgery
12. Efficacy : To assess the rate of second cancers in patients undergoing observation as compared to those treated with 6 months of adjuvant pembrolizumab after surgery
13. Efficacy : To assess the overall survival (OS) in patients undergoing observation as compared to those treated with 6 months of adjuvant pembrolizumab after surgery (as standard of care)
14. Hierarchical composite evaluation : To compare observation with standard of care on the following events and hierarchical order: deaths, distant recurrence, local recurrence, Grade 3-4 irAEs, Grade 2 irAEs, overall quality of life.
15. Economic evaluation : To compare the cost-effectiveness of observation as compared with the standard of care
16. Economic evaluation : To compare the budget impact of observation as compared with the standard of care

Conditions and MedDRA coding

Patient with early triple-negative breast cancer (TNBC) achieving pathologic complete response (pCR) after neoadjuvant systemic chemotherapy and pembrolizumab.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Patient must have signed a written informed consent prior to any trial-related procedures. When the patient is physically unable to give his written consent, a trusted person of his choice, independent from the investigator or the sponsor, can confirm in writing the patient’s consent;
2. Adequate organ and bone marrow functions. All screening lab tests should be performed within 28 days before random d. Creatinine clearance ≥ 30 mL/min for subject with creatinine levels > 1.5 x institutional upper limit of normal (ULN) e. Total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN (Patients with Gilbert’s disease with a total bilirubin ≤ 2.5 x ULN and direct bilirubin within normal limits are permitted) f. Aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) ≤ 2.5 x ULNisation; a. Absolute Neutrophil Count (ANC) ≥ 1,000 /μL b. Platelets ≥ 100,000 /μL c. Hemoglobin ≥ 9 g/dL
3. Randomisation must take place no more than 12 weeks after breast surgery. Adjuvant radiotherapy is authorized. If given, as per investigator discretion it can be given concurrently with pembrolizumab;
4. Patients must not be pregnant or nursing (for women of childbearing potential only, a negative serum pregnancy test must be obtained within 7 days of Cycle 1 Day 1);
5. Women of childbearing potential and male patients must agree to use 1 effective form of contraception and up to 4 months after the last dose of study drugs;
6. Patients should be able and willing to comply with study visits and procedures as per protocol;
7. Patients must be affiliated to a Social Security System (or equivalent).
8. Age ≥ 18 years;
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;
10. Histologically documented stage T1cN1-2 or T2-4N0-2 triple negative or ER/PR low breast cancer (Estrogen receptor (ER) and Progesterone receptor (PR) ≤10%; HER2-negative as per ASCO/CAP guidelines). Staging according to the primary tumourregional lymph node anatomic staging criteria of the American Joint Committee on Cancer (AJCC), 8th edition as determined by the investigator during radiologic assessment, clinical assessment or both.
11. Patients previously treated with neoadjuvant chemotherapy in combination with pembrolizumab for a minimum of 6 cycles (All systemic chemotherapy must have been completed preoperatively);
12. Absence of residual invasive disease in the breast or lymph nodes after the completion of neoadjuvant therapy (i.e., ypT0 ypN0 in the current AJCC staging system) (Residual ductal carcinoma in situ [DCIS] is allowed);
13. Have had an adequately excised breast cancer (surgical removal of all clinically evident disease in the breast and lymph nodes) : a. Breast surgery: patients must have undergone either breast-conserving surgery or total mastectomy with histologically negative margins for invasive tumour and DCIS. Patients with margins positive for lobular carcinoma in situ (LCIS) are eligible without additional resection. b. Lymph node surgery: patients must have had sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection (ALND) to evaluate the pathologic nodal status;
14. Patients that have received adequate locoregional radiation therapy or with planned adequate locoregional radiation therapy;

Exclusion criteria 13

1. Radiological or clinical evidence of metastatic disease (stage IV) documented by imaging or clinical examination;
2. Evidence of recurrent disease following preoperative therapy and surgery;
3. Any prior history of (ipsi- or contralateral) invasive breast cancer;
4. Patients with a history of another malignancy without complete remission for more than 5 years, except for properly treated cervical carcinoma in situ and non-melanoma cancer of the skin
5. Patients for whom pembrolizumab has been permanently discontinued during the neoadjuvant phase of treatment due to pembrolizumab-related AE;
6. History of intolerance, including Grade 3 or 4 infusion reaction or hypersensitivity to pembrolizumab or murine proteins or any component of the product;
7. Medical conditions that require chronic systemic steroids (>10 mg prednisone or equivalent) or any other form of immunosuppressive medication in the past 2 years. Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment;
8. Known active liver disease, e.g. due to HBV, HCV, autoimmune hepatic disorders, or sclerosing cholangitis;
9. HIV-infected patients on effective anti-retroviral therapy with detectable viral load within 6 months prior to enrollment;
10. Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better;
11. Patients unwilling or unable to comply with the medical follow-up required by the trial due to geographic, familial, social, or psychological reasons;
12. Persons deprived of their liberty or under protective custody or guardianship;
13. Participation in another therapeutic trial within the 30 days prior to randomisation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Recurrence-free survival is defined as the time from randomisation to invasive loco-regional or distant recurrence or death from any cause, whichever occurs first. Patients who are alive at the time of analysis without documented breast cancer recurrence will be censored at the time of their last disease evaluation.

Secondary endpoints 14

1. Safety and tolerability : Grade ≥2 AEs (graded according to CTCAE version 5.0) with a focus on Grade ≥2 immune-related adverse events
2. Safety and tolerability : PRO CTCAE composite score of selected events (bloating, diarrhea, abdominal pain, rash, itching, anorexia, nausea, fatigue, dyspnea, radiation skin reaction, myalgia, arthralgia, pain, and peripheral sensory neuropathy)
3. Health-related quality-of-life (QoL) and emotional distress : Overall QoL measured by the summary score of the EORTC QLQ-C30 questionnaire
4. Health-related quality-of-life (QoL) and emotional distress : & 1.2.3 Individual scores of all domains of the EORTC QLQ-30, EORTC-BR42 and EQ5D5L questionnaires
5. Health-related quality-of-life (QoL) and emotional distress : Fear of recurrence will be measured by item 11 of the Impact of Cancer (IOC) questionnaire
6. Fertility and Reproductive Toxicity : Menstruation recovery rate
7. Fertility and Reproductive Toxicity : Rate and outcome of pregnancy
8. Fertility and Reproductive Toxicity : Patterns of use of LHRH agonist during adjuvant pembrolizumab treatment
9. Efficacy : Invasive breast cancer-free survival (IBCFS) is defined as the time from randomisation to invasive ipsilateral or contra-lateral breast tumour recurrence, loco-regional invasive recurrence, distant recurrence, and death from breast cancer, death from non-breast cancer or from an unknown cause. Patients alive with no evidence of an IBCFS event at the time of their last visit will be censored at the time of the last examination.
10. Efficacy : Distant relapse free-survival (DRFS) is defined as the time from randomisation to distant recurrence, death from non-breast cancer or from an unknown cause. Patients alive with no evidence of a DRFS event at the time of their last visit will be censored at the time of the last examination.
11. Efficacy : Incidence of second primary cancer, in a competing risk model with deaths. Patients alive with no evidence of second cancer at the time of their last visit will be censored at the time of the last examination.
12. Efficacy : Overall survival is defined as the time from randomisation to death. Patients known to be still alive or lost to follow-up will be censored.
13. Hierarchical composite outcome : Hierarchical outcome of deaths, distant recurrence, local recurrence, Grade 3-4 irAEs, Grade 2 irAEs, overall quality of life (summary score of EORTC QLQ-C30).
14. Economic evaluation : Patient-level life-time incremental cost per QALY; probability of cost-effectiveness Country-level total budget impact for a real-world population

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Unicancer

Sponsor organisation

Unicancer

Address

101 Rue De Tolbiac

City

Paris

Postcode

75013

Country

France

Scientific contact point

Organisation

Unicancer

Contact name

Nourredine Nourredine AIT RAHMOUNE

Public contact point

Organisation

Unicancer

Contact name

Nourredine Nourredine AIT RAHMOUNE

Locations

2 EU/EEA countries · 64 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 22 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications