This is a Phase II study designed to assess efficacy and safety of talazoparib, high dose radiation, and atezolizumab in patients with metastatic TNBC that is PD-L1 positive. A total of 23 gBRCA pathogenic variant negative patients will be enrolled. All patients will be treated with induction talazoparib of 1mg PO daily starting Day 1. Patients will then receive 8 Gy x 3 fractions to 2-4 metastatic lesions beginning Day 12,13, or 14 and given QOD. 840 mg of atezolizumab will be given intravenously (IV) on Day 15 of the 1st cycle and then on Day 1 and Day 15 of the remaining cycles. The sequence of administration is not specified on the days in which talazoparib and atezolizumab are given on the same day. Each cycle equals 28 days. Treatment will continue until progression or severe toxicity. A safety lead in of up to 6 patients will be performed. Immune-related and non-immune related adverse events will be tracked up to 12 weeks post initiation of atezolizumab, as the majority of treatment-related toxicities from talazoparib, radiation, and atezolizumab occur within this time period.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
1
Talazoparib 1 mg Orally Day 1 to Day 28
Atezolizumab 840 mg IV over 60 minutes Day 15 of Cycle 1 then Day 1 and Day 15 of subsequent Cycles
Radiation 8 Gy will be given in 3 fractions QOD beginning Day 12, 13 or 14 of Cycle 1 but 24-72 hours prior to 1st dose of Atezolizumab
University of Alabama at Birmingham
Birmingham, Alabama, United States
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States
Objective Response Rate (ORR) by RECIST 1.1
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. ORR is defined as the proportion of all subjects with confirmed PR or CR according to RECIST 1.1, from the start of treatment until disease progression/recurrence
Time frame: Up to a maximum of 5 months
Assess Adverse Events
The frequency and severity of all treatment related adverse events for the single enrolled subject are reported by CTCAE v5 term and grade.
Time frame: Up to a maximum of 12 months.
Progression Free Survival (PFS)
Progression free survival (PFS) is defined as the day of study treatment initiation until disease progression by RECIST 1.1 or death whichever occurs first.
Time frame: Time of treatment start until the criteria for disease progression or death, up to a maximum of 5 months.
Overall Survival (OS)
Overall survival is defined as the time from treatment start until death or date of last contact.
Time frame: Time of treatment start until death, up to a maximum of 12 months.
ORR by Immune-related RECIST (irRECIST)
Per Immune-Related RECIST (irRECIST): Complete Response(irCR), Disappearance of all measurable and non-measurable lesions; Partial Response (irPR) \>=30% decrease in tumor burden relative to baseline; Progressive Disease (irPD), \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions confirmed by a consecutive assessment at least 4 week after first documentation; Stable Disease (irSD), not meeting criteria for irCR or irPR, in absence of irPD ORR is defined as the proportion of all subjects with CR and PR determined as per irRECIST
Time frame: Up to a maximum of 5 months
Duration of Overall Response (DOR)
DOR is defined as the time from the measurement criteria are met for complete or partial response (whichever status is recorded first) until the date of recurrent or disease progression.
Time frame: Up to a maximum of 5 months
Disease Control Rate (DCR)
Disease control rate (DCR) is defined as the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease.
Time frame: Up to a maximum of 5 months
Time to Progression (TTP)
Time to progression (TTP) is defined as the day of study treatment initiation until disease progression by RECIST 1.1.
Time frame: Up to a maximum of 5 months
Best Overall Tumor Response
Best overall tumor response is defined as the best response recorded from the start of the study treatment until disease progression/recurrence.
Time frame: Time of treatment start until the criteria for disease progression, up to a maximum of 5 months.
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