A Phase II Open-Label, Randomized Study of PARP Inhibition (Olaparib) Either Alone or in Combination with Anti-PD-L1 Therapy (Atezolizumab; MPDL3280A) in Homologous DNA Repair (HDR) Deficient, Locally Advanced or Metastatic Non-HER2-Positive Breast Cancer
Categories (click each to see list of all clinical trials associated with that category): Breast
Current Status: Open to accrual
Phase: II
Principal Investigator: Tandra, Pavankumar
Contact Information:
Shara Graalfs
+1 402-596-3151
shara.graalfs@unmc.edu
Eligibility: https://clinicaltrials.gov/ct2/show/NCT02849496#eligibility
Summary
PRIMARY OBJECTIVES:
I. To compare the progression free survival (PFS) between two study arms, i.e., olaparib monotherapy (arm 1) and olaparib + atezolizumab in combination (arm 2) based on normal Response Evaluation Criteria in Solid Tumors (RECIST) criteria in patients with locally advanced or metastatic non-HER2-positive breast cancer harboring homologous deoxyribonucleic acid (DNA) repair (HDR) through BRCA 1/2 mutation.
SECONDARY OBJECTIVES:
I. To compare the progression free survival (PFS) between the two study arms based on immune response criteria.
II. To compare the time to treatment failure (TTF) between the two study arms based on immune response criteria and normal RECIST.
III. To compare the overall response rate (ORR) between the two study arms based on immune response criteria and normal RECIST.
IV. To compare the duration of response (DoR) between the two study arms based on immune response criteria and normal RECIST.
V. Determine the changes in extent of mutational burden in BRCA 1/2 mutated tumors at baseline and at progression.
VI. Evaluate and characterize changes in the extent of PD-L1 expression and tumor immune infiltrates.
VII. Retrospectively evaluate tumors with limited immune infiltrate (e.g. "non-inflamed") to determine if PARPi increased immune infiltration.
VIII. Determine the immune-related best overall response (irBOR) of olaparib in combination with atezolizumab in locally advanced or metastatic non-HER2+ breast cancer harboring HDR through BRCA 1/2 mutation.