Chemotherapy (including paclitaxel [pac]) remains the main 1L treatment for metastatic TNBC but brings limited clinical benefit, highlighting the need for new treatments. Atezolizumab (atezo) blocks the interaction of PD-L1 with receptors PD-1 and B7.1, thus restoring anti-tumor immunity. TNBC is a rational target for atezo due to high PD-L1 expression, elevated T-cell tumor infiltration and high mutational burden. Atezo alone and in combination with nab-pac was well tolerated, with no exacerbation of chemo-associated adverse events, and demonstrated promising clinical activity in mTNBC. Atezo + nab-pac is being further investigated as 1L TNBC treatment in IMpassion130. IMpassion131, a global, multi-center, randomized, double-blind, placebo (pbo)-controlled study, is comparing the efficacy and safety of 1L atezo + pac vs pbo + pac in patients (pts) with untreated, inoperable, locally advanced or metastatic TNBC.
Eligible pts are those with inoperable, locally advanced or metastatic TNBC, histologically confirmed; de novo or recurrent disease after early BC chemo treatment completed ≥ 12 mo prior; taxane monotherapy eligible; no prior chemo or targeted systemic therapy for inoperable locally advanced or metastatic disease; ECOG PS 0-1 and measurable disease by RECIST v1.1. Exclusion criteria include known symptomatic CNS disease, prior immunotherapy and history of autoimmune disease. Approximately 495 pts will be randomized 2:1 to receive atezo (840 mg) or pbo (q2w; days 1 and 15 of 28-day cycle) plus pac (90 mg/m2; days 1, 8, 15 of 28-day cycle) until disease progression. Stratification factors are PD-L1 expression on tumor-infiltrating immune cells (IC; IC0 [< 1%] vs IC1/2/3 [≥ 1%] with VENTANA SP142 IHC assay), prior taxane therapy, presence of liver metastases and geographical region. The primary endpoint is PFS measured by RECIST v1.1. Key secondary endpoints include OS, 12- and 18-month OS rates, 12-month PFS rate, ORR, DOR, and safety. Tumor biopsies will be investigated at baseline, on treatment and at progression to assess biomarkers of response and immune escape.
Clinical trial identification
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
F. Hoffmann-La Roche Ltd.
D. Miles: Honoraria for Advisory Boards from Roche-Genentech. F. Andre: Research grants: AstraZeneca, Novartis, PF, Lilly. J. Gligorov: Advisory boards: Eisai, GenomicHealth, Novartis, Pfizer, Roche. Granted research: Eisai, Roche. D. Cameron: Employer paid for consultancy work done with Roche. Hospital has also been reimbursed for costs incurred in doing clinical research by Roche. C.H. Barrios: Research: Pfizer, Novartis, Amgen, AstraZeneca, Boehringer Ingelheim, Roche, Lilly, Sanofi, GSK, Taiho, Mylan, Merrimack, Merck, Astellas, Bristol-Myers Squibb. Consulting: Boehringer-Ingelheim, GSK, Novartis, Pfizer, Roche-Genentech, Eisai. A. Schneeweiss: Member of Roche advisory boards. Member of IMpassion 130 steering committee. Honoraria and financial support from Roche for presentations at academic meetings. V. Easton, I. Dolado: Roche employee and stock. J. O\'Shaughnessy: Consultant to Genentech and Roche. All other authors have declared no conflicts of interest.