pembrolizumab for Early-stage triple-negative breast cancer

Inclusion criteria

• {"criterion_text":"- 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;\n- 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.\n- Patients previously treated with neoadjuvant chemotherapy in combination with pembrolizumab for a minimum of 6 cycles (All systemic chemotherapy must have been completed preoperatively);\n- 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);\n- 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;\n- Patients that have received adequate locoregional radiation therapy or with planned adequate locoregional radiation therapy;\n- 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\n- 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;\n- 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);\n- 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;\n- Patients should be able and willing to comply with study visits and procedures as per protocol;\n- Patients must be affiliated to a Social Security System (or equivalent).\n- Age ≥ 18 years;\n- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;"}

Exclusion criteria

• {"criterion_text":"- Radiological or clinical evidence of metastatic disease (stage IV) documented by imaging or clinical examination;\n- 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;\n- Patients unwilling or unable to comply with the medical follow-up required by the trial due to geographic, familial, social, or psychological reasons;\n- Persons deprived of their liberty or under protective custody or guardianship;\n- Participation in another therapeutic trial within the 30 days prior to randomisation\n- Evidence of recurrent disease following preoperative therapy and surgery;\n- Any prior history of (ipsi- or contralateral) invasive breast cancer;\n- 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\n- Patients for whom pembrolizumab has been permanently discontinued during the neoadjuvant phase of treatment due to pembrolizumab-related AE;\n- History of intolerance, including Grade 3 or 4 infusion reaction or hypersensitivity to pembrolizumab or murine proteins or any component of the product;\n- 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;\n- Known active liver disease, e.g. due to HBV, HCV, autoimmune hepatic disorders, or sclerosing cholangitis;\n- HIV-infected patients on effective anti-retroviral therapy with detectable viral load within 6 months prior to enrollment;"}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Time from randomisation to invasive loco-regional or distant recurrence or death from any cause; patients alive without documented breast cancer recurrence are censored at last disease evaluation."}

Secondary endpoints

• {"endpoint_text":"- Safety and tolerability : Grade ≥2 AEs (graded according to CTCAE version 5.0) with a focus on Grade ≥2 immune-related adverse events\n- 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)\n- Health-related quality-of-life (QoL) and emotional distress : Overall QoL measured by the summary score of the EORTC QLQ-C30 questionnaire\n- 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\n- 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\n- Fertility and Reproductive Toxicity : Menstruation recovery rate\n- Fertility and Reproductive Toxicity : Rate and outcome of pregnancy\n- Fertility and Reproductive Toxicity : Patterns of use of LHRH agonist during adjuvant pembrolizumab treatment\n- 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.\n- 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.\n- 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.\n- 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.\n- 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).\n- Economic evaluation : Patient-level life-time incremental cost per QALY; probability of cost-effectiveness Country-level total budget impact for a real-world population","definition_or_measurement_approach":"Definitions/measurement approaches provided in protocol where available: Grade ≥2 AEs graded by CTCAE v5.0; PRO-CTCAE composite score uses listed symptoms; Overall QoL measured by EORTC QLQ-C30 summary score; individual domain scores of EORTC QLQ-C30, EORTC-BR42 and EQ5D-5L recorded; Fear of recurrence measured by item 11 of IOC; Menstruation recovery rate and pregnancy rate recorded; IBCFS defined as time from randomisation to invasive ipsilateral/contralateral breast tumour recurrence, loco-regional invasive recurrence, distant recurrence, or death from breast/non-breast/unknown cause with censoring at last exam; DRFS defined as time from randomisation to distant recurrence or death (non-breast or unknown) with censoring; Incidence of second primary cancer analysed in competing risk model with deaths; Overall survival = time from randomisation to death with censoring for alive or lost to follow-up; Hierarchical composite uses ordered events (deaths, distant recurrence, local recurrence, Grade 3-4 irAEs, Grade 2 irAEs, overall QoL summary score); Economic outcomes: patient-level lifetime incremental cost per QALY and country-level budget impact."}

Belgium

Earliest CTIS Part Ii Submission Date

19-02-2025

Latest Decision Or Authorization Date

20-06-2025

Processing Time Days

121

Number Of Sites

10

Number Of Participants

200

France

Earliest CTIS Part Ii Submission Date

10-02-2025

Latest Decision Or Authorization Date

21-06-2025

Processing Time Days

131

Number Of Sites

50

Number Of Participants

800

Primary sponsor

Full Name

Unicancer

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France