Roche has announced that the US Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) and granted Priority Review for Tecentriq® (atezolizumab) plus chemotherapy (Abraxane® [albumin-bound paclitaxel; nab-paclitaxel]) for the initial (first-line) treatment of unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) in people whose disease expresses the PD-L1 protein, as determined by PD-L1 biomarker testing. The FDA is expected to make a decision on approval by 12 March 2019. A Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a disease.
“Tecentriq in combination with nab-paclitaxel has the potential to meaningfully advance treatment for people with PD-L1-positive, metastatic triple-negative breast cancer. People need more options for this type of breast cancer, which is particularly difficult to treat,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “We are working closely with the FDA to bring this Tecentriq combination to people with PD-L1-positive metastatic triple-negative breast cancer as soon as possible.”
The sBLA is based on data from the Phase III IMpassion130 study, which was presented at the European Society for Medical Oncology (ESMO) Congress and published in the New England Journal of Medicine in October 2018. Results demonstrate Tecentriq plus nab-paclitaxel as an initial (first-line) treatment for unresectable locally advanced or metastatic TNBC significantly reduced the risk of disease worsening or death (progression-free survival; PFS) compared with nab-paclitaxel alone in all randomised patients (intention-to-treat [ITT]) (median PFS=7.2 vs. 5.5 months; hazard ratio [HR]=0.80; 95% CI: 0.69-0.92, p=0.0025) and the PD-L1-positive population (median PFS=7.5 vs 5.0 months; HR=0.62; 95% CI: 0.49-0.78, p<0.0001), a subgroup determined by PD-L1 biomarker testing.[1] At this interim analysis, statistical significance was not met for overall survival (OS) in the ITT population (median OS=21.3 vs 17.6 months; HR=0.84; 95% CI: 0.69-1.02, p=0.0840), but the combination showed a clinically meaningful OS improvement in the PD-L1-positive population (median OS=25.0 vs 15.5 months; HR=0.62; 95% CI: 0.45-0.86). Due to the hierarchical statistical design, results in the PD-L1-positive population were not formally tested for statistical significance. Follow-up will continue until the next planned analysis.
Safety in the Tecentriq plus nab-paclitaxel arm appeared consistent with the known safety profiles of the individual medicines, and no new safety signals were identified with the combination. Serious adverse events were reported in 23% of people who received Tecentriq plus nab-paclitaxel compared to 18% of people who received nab-paclitaxel alone.
Currently, Roche has seven ongoing Phase III studies investigating Tecentriq in TNBC, including early and advanced stages of the disease. If approved, this Tecentriq combination would be the first cancer immunotherapy regimen for the treatment of PD-L1-positive, metastatic TNBC.
About the IMpassion130 study
The IMpassion130 study is a Phase III, multicentre, randomised, double-blind study evaluating the efficacy, safety and pharmacokinetics of Tecentriq plus nab-paclitaxel compared with placebo plus nab-paclitaxel in people with unresectable locally advanced or metastatic TNBC who have not received prior systemic therapy for metastatic breast cancer. The study enrolled 902 people who were randomised equally (1:1). The co-primary endpoints are PFS per investigator assessment (RECIST 1.1) and OS. PFS and OS were assessed in all randomised patients (ITT) and in the PD-L1-positive population. Secondary endpoints include objective response rate, duration of response and time to deterioration in Global Health Status/Health-Related Quality of Life.
About TNBC
Breast cancer is the most common cancer among women with more than 2 million diagnosed worldwide each year.[2] TNBC represents 15% of all breast cancers and is more common in women under the age of 50, compared with other forms of breast cancer.[3; 4] It is defined by the lack of expression and/or amplification of the targetable receptors for oestrogen, progesterone and HER2 amplification.[5] Patients with metastatic TNBC generally experience rapid progression and shorter OS compared to other subtypes of breast cancer.