FDA Grants Priority Review to Combination Treatment for Initial TNBC

The FDA has accepted Genentech’s supplemental Biologics License Application (sBLA) and granted Priority Review for Tecentriq^® (atezolizumab) plus chemotherapy (Abraxane^® [albumin-bound paclitaxel; nab-paclitaxel]) for the initial 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.

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 was approved by the agency in 2016 for for the treatment of urothelial carcinoma, a type of bladder cancer; and for the treatment of metastatic non-small cell lung cancer (NSCLC).

“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, chief medical officer and head of Global Product Development, in a prepared statement. “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.”

New Bladder Cancer Treatment Approved

The sBLA is based on data from the Phase III IMpassion130 study, which was presented at the European Society for Medical Oncology (ESMO). This randomized, double-blind study evaluated 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 IMpassion130 study enrolled 902 individuals who were randomized equally (1:1). The co-primary endpoints are PFS per investigator assessment (RECIST 1.1) and OS. PFS and OS were assessed in all randomized 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.

According to Genentech, IMpassion130 study results demonstrate Tecentriq plus nab-paclitaxel as an 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 randomized 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.

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 percent of people who received Tecentriq plus nab-paclitaxel compared to 18 percent of people who received nab-paclitaxel alone.

FDA Approves Tecentriq for Metastatic Non-Small Cell Lung Cancer

Genentech, a member of the Roche Group, has 7 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. The FDA is expected to make a decision on approval by March 12, 2019, according to Genentech.

Reference

FDA Grants Priority Review to Genentech’s Tecentriq in Combination with Abraxane for the Initial Treatment of People with PD-L1-Positive, Metastatic Triple-Negative Breast Cancer [news release]. South San Francisco, CA; November 13, 2018: Genentech. https://www.businesswire.com/news/home/20181112005851/en. Accessed November 13, 2018.