NeoAdjuvant Therapy Comparing Sacituzumab Govitecan+Pembrolizumab vs. SoC Chemotherapy in Clinical Stage II-III, Triple-negative Early Breast Cancer

Inclusion Criteria

• •Minimal eligibility criteria to be met for registration in the clinical trial:
• •1. TNBC: ER = 0%, PR = 0%, and HER2- (i.e., immunohistochemistry \[IHC\] with DAKO score ≤ 1 or fluorescence in situ hybridization \[FISH\]-negative)
• •2. or TNBC-like: ER ≤ 10% positive cells in IHC, PR \< 10% positive cells in IHC, and HER2- (i.e., IHC with DAKO score ≤ 1 or FISH negative)
• •3. All patients, independent from gender
• •4. ≥18 years at diagnosis
• •5. 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. Histological confirmation of all lesions as TNBC is mandatory.
• •6. Clinical stage II-III at baseline
• •7. No clinical evidence for distant metastasis (M0)
• •8. Cognitive and language skills to complete quality of life (QoL) questionnaires
• •Additional eligibility criteria to be met for assignment to cohort I or II:
• •9. Completed 9-12 weeks of NACT with CARBO + PEM or PAC q1w + PEM q3w with the last dose of NACT given less than 2 weeks ago. Patients may also be considered if their NACT treatment was switched to nab-PAC due to intolerance to PAC.
• •* Patients with progressive disease during taxane-CARBO treatment are allowed to participate in cohort II after consultation with sponsor, provided that at least 6-9 weeks of NACT with taxane-CARBO q1w and PEM q3w have been administered
• •* Patients experiencing toxicities due to PEM, in case of contraindications or other medical reasons against PEM administration (with or without permanent discontinuation of PEM) can nevertheless be included, even if PEM will not be administered anymore. The number of patients starting the study without PEM is limited to 10%.
• •10. Tumour block available for central pathology review
• •11. Performance Status ECOG ≤ 1 or Karnofsky Index ≥ 80%
• •12. 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
• •13. The patient must be capable of giving informed consent and be willing and able to comply with the requirements and restrictions in this protocol and accessible for treatment and follow-up
• •14. Laboratory requirements (female and male patients, ≤ 14 days old)
• •* Neutrophils \> 1.5 109/L,
• •* Platelets \> 100 109/L,
• •* Total bilirubin \< 1 x upper level of normal (ULN),
• •* ASAT (sGOT) \< 2.5 x ULN,
• •* ALAT (sGPT) \< 2.5 x ULN,
• •* Creatinine ≤1.5 × ULN OR clearance ≥30 mL/min for participant with creatinine levels \>1.5 × institutional ULN
• •15. Clinical assessments:
• •\- Normal Electrocardiogram (ECG) (within 42 days prior to induction treatment)
• •16. Negative pregnancy test (urine or serum) within ≤ 14 days prior to registration in premenopausal patients and immediate implementation of adequate contraceptive measures.
• •Note: Pregnancy testing is to be repeated according to Schedule of Activities.
• •17. 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.
• •18. 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 without use of a contraceptive method.
• •19. 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 enrolment 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.
• •20. Female patients must not donate, or retrieve for their own use, ova from the time of randomization 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.
• •21. 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.