NeoAdjuvant Dynamic Marker - Adjusted Personalized Therapy Comparing Sacituzumab Govitecan Versus Sacituzumab Govitecan+Pembrolizumab in Low-risk, Triple-negative Early Breast Cancer (ADAPT-TN-III)
TNBC is known for poor prognosis, aggressive patterns of disease, and significant molecular heterogeneity. (Neo)adjuvant chemotherapy (NACT) is standard of care in all node-positive and in node-negative patients with a tumour size \>5 mm according to current National Comprehensive Cancer Network (NCCN) guidelines. However, TNBC patients with lower stage disease do clearly have a better prognosis compared to more advanced stages. Patients with stage I-II node-negative disease have 3-5 year iDFS rates of 80-90% (with majority of relapses within the first three years) as shown in several trials.Although survival results appear much better in the lower vs. higher stages, there is a high clinical need in this most common group of TNBC patients in Western Europe and USA.
• 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
• All patients, independent from gender
• ≥18 years at diagnosis
• Histologically confirmed unilateral, primary invasive carcinoma of the breast Note: bilateral, multicentric, or multifocal carcinoma may be included, if there is a clear target lesion, that is subject to treatment decisions and solely evaluated and documented for study purposes.
• 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)
• No clinical evidence for distant metastasis (M0)
• Tumour block available for central pathology review
• Performance Status ECOG ≤ 1 or KI ≥ 80%
• Negative pregnancy test (urine or serum) within 7 days prior to registration in premenopausal patients
⁃ 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
⁃ The patient must be willing and able to comply with the requirements and restrictions in this protocol and accessible for treatment and follow-up
⁃ Laboratory requirements:
∙ Leucocytes ≥3.5 109/L,
‣ Neutrophils \> 1.5 109/L,
‣ Platelets ≥100 109/L,
‣ Haemoglobin ≥10 g/dL,
‣ AP \< 5.0 ULN,
‣ AST ≤2.5 x ULN,
‣ ALT ≤2.5 x ULN,
‣ Total bilirubin ≤1 x ULN,
‣ Creatinine ≤1.5 × ULN OR clearance ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN
⁃ Clinical assessments:
⁃ • LVEF within normal limits of each institution, measured by echocardiography and normal ECG (within 42 days prior to treatment)
⁃ The following age-specific requirements apply:
∙ Women 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.
‣ Women 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.
⁃ 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 if they wish to continue their HRT during the study. Otherwise, they must 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 resume use of HRT during the study without use of a contraceptive method.
⁃ 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 1 (see Section 4.4.2), from the time of screening and must agree to continue using such precautions for 7 months after the last dose of 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.
⁃ 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.
⁃ 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.