PEMBROLIZUMAB for Triple-negative breast cancer | Early breast cancer

Inclusion criteria

• {"criterion_text":"- ER + PR negative or low positive (≤10% positive cells in IHC), and HER2 negative (i.e., IHC 0 – 1+ or IHC 2+ with FISH negative) breast cancer\n- Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements\n- The patient must be willing and able to comply with the requirements and restrictions in this protocol and accessible for treatment and follow-up\n- Laboratory requirements: •\tLeucocytes  3.5 109/L, •\tNeutrophils >1.5 109/L, •\tPlatelets  100 109/L, •\tHaemoglobin  10 g/dL, •\tAP < 5.0 ULN, •\tAST  2.5 x ULN, •\tALT  2.5 x ULN, •\tTotal bilirubin  1 x ULN, •\tCreatinine ≤1.5 × ULN OR clearance ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN\n- Clinical assessments: •\tLVEF within normal limits of each institution, measured by echocardiography and normal ECG (within 42 days prior to treatment)\n- The following age-specific requirements apply: •\tWomen aged <50 years will be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the post-menopausal range for the site. •\tWomen aged ≥ 50 years will be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatments.\n- Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the contraception methods outlined for women of child-bearing potential and need to discontinue HRT to allow confirmation of post-menopausal status prior to randomization/study enrolment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can participate in the study without use of a contraceptive method.\n- Female patients of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception, presented in Table 3 (see Section 3.8.2), from the time of enrolment and must agree to continue using such precautions for 7 months after the last dose of investigational medicinal product (IMP). Not all methods of contraception are highly effective. Female patients must refrain from breastfeeding while on study and for 7 months after the last dose of IMP. Complete heterosexual abstinence for the duration of the study and drug washout period is an acceptable contraceptive method if it is line with the patient’s usual lifestyle (consideration must be made to the duration of the clinical trial); however, periodic, or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable.\n- Female patients must not donate, or retrieve for their own use, ova from the time of randomisation and throughout the study treatment period, and for at least 7 months after the final study drug administration. They should refrain from breastfeeding throughout this time. Preservation of ova may be considered prior to enrolment in this study.\n- A male participant must agree to use a contraception as detailed in Appendix C of this protocol during the treatment period and for at least 7 months after the last dose of study treatment and refrain from donating sperm during this period.\n- All patients, independent from gender\n- ≥18 years at diagnosis\n- Histologically confirmed unilateral, primary invasive carcinoma of the breast Note: bilateral, multicentric, or multifocal carcinoma may be included, if there is a clear target (primary) lesion, that is subject to treatment decisions and solely evaluated and documented for study purposes.\n- Clinical stage I: cT1a-c/cN0,(clinical stage II only, if patient does not qualify for neoadjuvant polychemotherapy+PEM, e.g., elderly population, per investigator´s decision)\n- No clinical evidence for distant metastasis (M0)\n- Tumour block available for central pathology review\n- Performance Status ECOG ≤ 1 or KI ≥ 80 %\n- Negative pregnancy test (urine or serum) within 7 days prior to registration in premenopausal patients"}

Exclusion criteria

• {"criterion_text":"- Known hypersensitivity reaction to the compounds or incorporated substances of the IMPs\n- Patients not able to consent\n- Known polyneuropathy ≥ grade 2\n- Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study including recovery from major surgery, autoimmune disease, known psychiatric/substance abuse disorders, acute cystitis, ischuria, and chronic kidney disease\n- Uncontrolled infection requiring i.v. antibiotics, antivirals, or antifungals\n- History of pneumonitis\n- Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection,. Patients should be tested for HIV prior to randomisation if required by local regulations or ethics committee (EC). Patients who test positive for HIV-antibody are excluded.\n- Active hepatitis B virus (HBV) or hepatitis C virus (HCV). In patients with a history of HBV or HCV, patients with detectable viral loads will be excluded. •\tPatients who test positive for hepatitis B surface antigen (HBsAg). Patients who test positive for hepatitis B core antibody (anti-HBc) will require HBV DNA by quantitative polymerase chain reaction (PCR) for confirmation of active disease. •\tPatients who test positive for HCV antibody will require HCV RNA by quantitative PCR for confirmation of active disease. Patients with a known history of HCV or a positive HCV antibody test will not require a HCV antibody at enrolment and will only require HCV RNA by quantitative PCR for confirmation of active disease.\n- Prior malignancy with a disease-free survival of < 5 years, except curatively treated basalioma of the skin or pTis of the cervix uteri\n- Any history of invasive breast cancer\n- Previous or concurrent treatment with cytotoxic agents for any reason unless clarified with sponsor\n- Concurrent treatment with other experimental drugs.\n- Participation in another interventional clinical trial with or without any investigational not marketed drug within 30 days prior to study entry\n- Concurrent pregnancy; patients of childbearing potential or potentially childbearing partners of male patients must implement a highly effective (less than 1% failure rate) non-hormonal contraceptive measures during the study treatment\n- Breast feeding woman\n- Reasons indicating risk of poor compliance"}

Primary endpoints

• {"endpoint_text":"- pCR defined as no invasive tumour in breast and lymph nodes (ypT0/is, ypN0)\n- 3-year iDFS, defined as time from date of first diagnosis to any invasive breast cancer event, death, or secondary malignancy according to STEEP 2.0 criteria","definition_or_measurement_approach":"- pCR defined as no invasive tumour in breast and lymph nodes (ypT0/is, ypN0)\n- 3-year iDFS defined as time from date of first diagnosis to any invasive breast cancer event, death, or secondary malignancy according to STEEP 2.0 criteria"}

Secondary endpoints

• {"endpoint_text":"- Clinical response measured by palpation, ultrasound, and mammography\n- Overall survival defined as time from date of first diagnosis to death\n- 3-year dDFS\n- 3-year dDFI\n- 3-year RFS\n- 3-year LRFS\n- 3-year BCFI\n- Change of health-related quality of life between baseline and after defined timepoints: after 2, 4, and 6 cycles (if applicable), before surgery, every 6 months in follow-up until year 3 and yearly afterwards.","definition_or_measurement_approach":"- Clinical response measured by palpation, ultrasound, and mammography (measurement modalities specified).\n- Overall survival: defined as time from date of first diagnosis to death.\n- 3-year dDFS/dDFI/RFS/LRFS/BCFI: no additional definitions provided in CTIS extract.\n- Change of health-related quality of life: HRQoL assessed using EORTC-QLQ-C30 (v3.0) and EORTC QLQ-BR45 (v1.0) as per secondary objectives; measurements at baseline, after 2/4/6 cycles (if applicable), before surgery, every 6 months until year 3 and yearly afterwards."}

Germany

Earliest CTIS Part Ii Submission Date

05-03-2024

Latest Decision Or Authorization Date

15-10-2025

Processing Time Days

589

Number Of Sites

45

Number Of Participants

348

Primary sponsor

Full Name

WSG Westdeutsche Studiengruppe GmbH

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Third parties

• {"country":"","full_name":"Gilead Sciences Ireland UC (GILEAD)","duties_or_roles":"","organisation_type":""}
• {"country":"","full_name":"MERCK SHARP & DOHME (MSD)","duties_or_roles":"","organisation_type":""}