Phase II Trial Evaluating the Safety and Efficacy of the Combination of Zimberelimab, Domvanalimab and Sacituzumab Govitecan as 1L Therapy for PD-L1 Positive Advanced TNBC

Inclusion Criteria: 1. Female or male participants, regardless of race and/or ethnic group, aged 18 years or older, able to understand and give written informed consent form (ICF). 2. Histologically confirmed TNBC per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) 2018 criteria, based on local testing performed on the most recent biopsy in the metastatic setting. . Triple-negative status is defined as \<1% expression for estrogen receptor (ER) and progesterone receptor (PgR) and negative for human epidermal growth factor receptor 2 (HER2) (0-1+ by immunohistochemistry or 2+ and negative by in situ hybridization test). 3. PD-L1 positive status defined as a CPS ≥ 10 determined by the antibody 22C3 PharmDx assay, based on local testing. 4. Unresectable locally advanced or metastatic disease documented by computerized tomography (CT) scan or magnetic resonance imaging (MRI) that is not amenable to resection with curative intent. 5. Measurable disease according to RECIST v.1.1. Tumor lesions situated in a previously irradiated area are considered measurable if unequivocal progression has been documented in such lesions since radiation. 6. No prior systemic therapy for advanced disease. For patients receiving (neo)adjuvant therapy, a disease-free interval of at least 6 months between completion of systemic treatment with curative intent and first documented local or distant disease recurrence is mandatory. Dates of postoperative radiotherapy are not included in this calculation. Prior use of an anti-PD-L1 agent in the curative TNBC setting is permitted. 7. Have adequate bone marrow, liver, and renal function. 8. Resolution of all acute toxic effects of previously administered agent to grade ≤ 1 as determined by the US National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (v.5.0) (except for alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion). 9. Willingness and ability to provide the most recently available formalin-fixed paraffin-embedded (FFPE) tumor tissue sample from the metastatic site at the time of inclusion. If this archival tissue is not available, a newly obtained baseline biopsy of an accessible tumor lesion is required before the start of Study treatment. If obtaining a biopsy is not feasible, patient eligibility must be evaluated by the Medical Monitor. 10. Willingness to provide blood and stool samples at the established time points. 11. Women of childbearing potential who are sexually active with a non-sterilized male partner must have a negative serum pregnancy test within 14 days before Study treatment initiation. In addition, they must agree to use one highly effective method of birth control from the time of screening until 6 months after the last dose of Study treatments. Female patients must refrain from egg cell donation and breastfeeding during this same period. 12. Male participants who are sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception from the time of screening until 6 months after the last administration of the Study drug. Male participants must not donate or bank sperm during this same period. 13. ECOG performance status of 0-1. 14. Minimum life expectancy of ≥ 12 weeks at screening. Exclusion Criteria: 1. Inability to comply with Study and follow-up procedures. 2. Pregnant or lactating women or patients not willing to apply highly effective contraception as defined in the protocol. 3. Concomitant participation in a Study with an investigational agent or investigational device within 4 weeks prior to Study enrolment. Participants enrolling in observational studies are eligible. 4. Have previously been treated with chemotherapy or immunotherapy in the metastatic setting. 5. Have previously been treated with topoisomerase 1 inhibitors or antibody drug conjugates containing a topoisomerase inhibitor in the curative setting. 6. Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases (except those treated with chemotherapy) may participate if they meet the following criteria: stable CNS disease demonstrated by radiographic stability for at least 4 weeks prior to enrollment, all neurologic symptoms have returned to baseline, no evidence of new or enlarging brain metastases, and clinical stability for at least 2 weeks while taking ≤ 10 mg/day of prednisone or its equivalent. However, all participants with carcinomatous meningitis are excluded regardless of clinical stability. 7. Have a concurrent malignancy or malignancy within 3 years of Study enrollment except for participants with surgically cured carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I uterine cancer, that are allowed to enroll. For other cancers considered to have a low risk of recurrence, discussion with the Sponsor's Medical Monitor is required. 8. Known allergy or hypersensitivity reaction to any investigational medicinal product (IMP) including zimberelimab, sacituzumab govitecan and domvanalimab or any of their components. 9. Requirement for ongoing therapy with any prohibited medications listed in the protocol. 10. Have received prior radiotherapy within 2 weeks of start of Study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A two-week washout period is permitted for palliative radiation to non-CNS disease. 11. Major surgical procedure or significant traumatic injury within 14 days before the first dose of Study treatment or anticipation of need for major surgery within the course of the Study treatment. 12. Have active chronic inflammatory bowel disease (ulcerative colitis/Crohn's disease) or gastrointestinal perforation within 6 months of enrollment. 13. Have an active cardiac disease or a history of cardiac dysfunction or conduction abnormalities. 14. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (e.g., pulmonary emboli within three months of the Study enrolment, severe asthma, severe chronic obstructive pulmonary disease \[COPD\], restrictive lung disease, pleural effusion, post COVID-19 pulmonary fibrosis, etc.), and any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (e.g., rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or prior pneumonectomy. 15. Have a history of non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening. 16. Have an active autoimmune disease that has required systemic treatment in the past 2 years (e.g., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) or are receiving chronic systemic corticosteroids at doses \> 10 mg/day prednisone or its equivalent 4 weeks prior to the first dose of study drug. Use of topical, inhalational, intranasal, and intraocular steroids and use as premedication for known hypersensitivity reactions (eg, intravenous \[IV\] contrast, IV drug infusions) will be permitted. Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. Additionally, patients who have experienced immune-related adverse events (irAEs) due to prior early-stage PD-L1 treatment and for whom rechallenge with a PD-L1 drug may pose a risk should also be excluded. 17. Current known infection with hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients with past HBV infection or resolved HBV infection (defined as having a negative hepatitis B surface antigen \[HBsAg\] test and a positive hepatitis B core antibody \[HBcAb\] test, accompanied by a negative HBV DNA test) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. 18. Have uncontrolled primary immunodeficiency, known human immunodeficiency virus (HIV) infection. 19. Other active uncontrolled infection at the time of enrollment. 20. Have undergone an allogenic tissue or solid organ transplant. 21. Receipt of live or attenuated vaccine within 30 days prior to the first dose of Study treatment. 22. A history of uncontrolled seizures, central nervous system (CNS) disorders, or serious and/or unstable pre-existing psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to Study drugs or interfering with subject safety. 23. Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the Study. 24. Known substance abuse or any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, contraindicate patient participation. 25. Inability or unwillingness to comply with the requirements of the protocol in the opinion of the investigator.