A Study of Novel Anti-cancer Agents in Patients With Metastatic Triple Negative Breast Cancer

Inclusion criteria

Female
At least 18 years of age at the time of screening
Patient must have locally confirmed advanced/unresectable or metastatic TNBC.
No prior treatment for metastatic (Stage IV) TNBC
Patient must have at least 1 lesion, not previously irradiated, that can be accurately measured
WHO/ECOG status at 0 or 1 at enrollment

Patients enrolled to Arm 6 (durvalumab and DS-8201a) Must provide documentation of locally determined advanced/unresectable or metastatic TNBC with HER2 low tumor expression (IHC 2+/ISH-, IHC 1+/ISH-, or IHC 1+/ISH untested)

Exclusion criteria

History of allogeneic organ transplantation
Active or prior documented autoimmune or inflammatory disorders
Active infection including tuberculosis, hepatitis B (known positive HBV surface antigen [HBsAg] result), hepatitis C virus (HCV), or human immunodeficiency virus (positive HIV 1/2 antibodies)
Untreated CNS metastases
Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
Any concurrent chemotherapy, IP, or biologic therapy for cancer treatment
Female patients who are pregnant, breastfeeding
Cardiac Ejection Fraction less than 50%

Patients enrolled in Arm 2 only:

Potent inhibitors or inducers or substrates of CYP3A4 or substrates of CYP2C9 or CYP2D6 within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort)
Diagnosis of diabetes mellitus Type I or diabetes mellitus Type II requiring insulin treatment.
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, such as heart failure, hypokalemia, potential for torsades de pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age, or any concomitant medication known to prolong the QT interval
Prior treatment with PI3K inhibitors, AKT inhibitors, or mammalian target of rapamycin (mTOR) inhibitors.

Patients enrolled in Arm 5 only: History of venous thromboembolism in the past 3 months

Patients enrolled in Arm 7 only: Clinically significant corneal disease in the opinion of the Investigator.

Patients enrolled in Arm 6 and 7 only:

History of or active interstitial lung disease/pneumonitis
Use of chloroquine or hydroxychloroquine in <14 days prior to Day 1 of DS-8201a (Arm 6) or Dato-DXd (DS-1062a; Arm 7) treatment
Patients enrolled in Arm 6 only: Previously been diagnosed as HER2+ or received HER2-targeted therapy.