First-line (1L) Stage IV Triple Negative Breast Cancer (TNBC) - the subtype of breast cancer characterized by a lack of tumor expression of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. MedDRA version: 20.0 Level: PT Classification code 10075566 Term: Triple negative breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female 2. At least 18 years of age at the time of screening 3. Patient must have locally confirmed advanced/unresectable or metastatic TNBC 4. No prior treatment for metastatic (Stage IV) TNBC 5. Patient must have at least 1 lesion, not previously irradiated, that can be accurately measured 6. 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) Patients enrolled in Arm 8 (durvalumab + Dato-DXd) Must have PD-L1 positive tumor as determined by an IHC based assay. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History of allogeneic organ transplantation 2. Active or prior documented autoimmune or inflammatory disorders 3. 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) 4. Untreated CNS metastases 5. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients 6. Any concurrent chemotherapy, IP, or biologic therapy for cancer treatment 7. Female patients who are pregnant, breastfeeding 8. Cardiac Ejection Fraction less than 50% Patients enrolled in Arm 2 only: 1. 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) 2. Diagnosis of diabetes mellitus Type I or diabetes mellitus Type II requiring insulin treatment Patients enrolled in Arm 5 only: History of venous thromboembolism in the past 3 months Patients enrolled in Arm 7 and Arm 8 only: Clinically significant corneal disease in the opinion of the Investigator. Patients enrolled in Arm 6, 7 and 8 only: 1. History of or active interstitial lung disease/pneumonitis 2. Use of chloroquine or hydroxychloroquine in <14 days prior to Day 1 of DS-8201a (Arm 6) or Dato-DXd (Arm 7 and Arm 8) treatment 3. Patients enrolled in Arm 6 only: Previously been diagnosed as HER2+ or received HER2-targeted therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1: To assess the safety and tolerability profile of durvalumab + novel oncology therapies with or without paclitaxel and durvalumab + paclitaxel. Part 2: To assess the efficacy of durvalumab + novel oncology therapies with or without paclitaxel in terms of ORR.;Secondary Objective: Part 1: 1. To assess the efficacy of durvalumab + novel oncology therapies with or without paclitaxel and durvalumab + paclitaxel in terms of ORR, PFS, DoR, and OS 2. To assess the PK of durvalumab and novel oncology therapies in all treatment arms. 3. To investigate the immunogenicity of durvalumab and novel oncology therapies in all applicable treatment arms. Part 2: 1. To assess the efficacy of durvalumab + novel oncology therapies with or without paclitaxel in terms of PFS, DoR, PFS6 and OS. 2.To assess the safety and tolerability profile of durvalumab + novel oncology therapies with or without paclitaxel.;Primary end point(s): Part 1: 1. AEs, exposure, physical examinations, laboratory findings, and vital signs Part 2: Endpoints based on Investigator assessment according to RECIST 1.1: ORR (objective response rate): The percentage of evaluable patients with a confirmed Investigator-assessed visit response of CR (complete response) or PR (partial response).;Timepoint(s) of evaluation of this end point: Part 1: 1. During treatment through 90 days after last dose of investigational product Part 2: During treatment through 180 days after last dose of investigational product | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1: 1. Endpoints based on Investigator assessment according to RECIST 1.1: - ORR (objective response rate): The percentage of evaluable patients with a confirmed Investigator-assessed visit response of CR (complete response) or PR (partial response) - PFS (progression-free survival): Time from date of first dose until the date of objective radiological disease progression using RECIST 1.1 or death (by any cause in the absence of progression) - DoR (duration of response): Time from date of first detection of objective response (which is subsequently confirmed) until the date of objective radiological disease progression -OS (overall survival): Time from date of first dose until the date of death by any cause 2. Serum concentration of durvalumab and serum or plasma concentration of novel oncology therapies 3. Presence of ADAs for durvalumab and applicable novel oncology therapies Part 2: 1. Endpoints based on Investigator assessment according to RECIST 1.1: - PFS (progression-free survival): Time from date of first dose until the date of objective radiological disease progression using RECIST 1.1 or death (by any cause in the absence of progression) - DoR (duration of response): Time from date of first detection of objective response (which is subsequently confirmed) until the date of objective radiological disease progression - PFS6: PFS at 6 months following date of first dose - OS (overall survival): Time from date of first dose until the date of death by any cause 2. AEs, exposure, physical examinations, laboratory findings, and vital signs;Timepoint(s) of evaluation of this end point: 1. During treatment through 90 days after last dose of investigational product 2. During treatment through 180 days after last dose of investigational product | — |
Countries
Canada, Korea, Republic of, Poland, Taiwan, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca AB
Outcome results
None listed