Tecentriq Wins Accelerated Approval for Advanced Bladder Cancer

First immunotherapy for patients unable to receive cisplatin

The FDA has granted accelerated approval to atezolizumab (Tecentriq, Genentech) for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin chemotherapy. This is the third approval for atezolizumab in less than a year.

The product was previously approved for patients with locally advanced or mUC who have disease progression during or after platinum-containing chemotherapy, or within 12 months of receiving chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant). It is also indicated for patients with metastatic non–small-cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy, and have progressed on an appropriate FDA-approved targeted therapy if their tumor has EGFR or ALK gene abnormalities.

Atezolizumab is a monoclonal antibody designed to bind with the programmed death- ligand 1 (PD-L1) protein. Atezolizumab binds to PD-L1 expressed on tumor cells and on tumor-infiltrating immune cells, blocking its interactions with both programmed death-1 (PD-1) and B7.1 receptors. By inhibiting PD-L1, atezolizumab may enable the activation of T cells. It may also affect normal cells.

The latest approval of atezolizumab was based on data from the phase 2, open-label, single-arm IMvigor210 trial, which evaluated the safety and efficacy of atezolizumab in patients with locally advanced or mUC regardless of PD-L1 expression. The patients were enrolled into one of two cohorts. The accelerated approval was based on results from cohort 1, which consisted of 119 patients with locally advanced or mUC who were ineligible for cisplatin-containing chemotherapy and were either previously untreated or had disease progression at least 12 months after neoadjuvant or adjuvant chemotherapy. Patients in this cohort received a 1,200-mg intravenous dose of atezolizumab every three weeks until either unacceptable toxicity or disease progression occurred. The study’s primary endpoint was the objective response rate (ORR).

Among all patients, the ORR was 23.5%, consisting of a complete response rate of 6.7% and a partial response rate of 16.8%.

Potential serious adverse events associated with atezolizumab include pneumonitis, hepatitis, colitis, hormone gland problems (especially the pituitary, thyroid, adrenal glands, and pancreas), nervous system problems (neuropathy, meningitis, and encephalitis), eye inflammation, severe infections, and severe infusion reactions.

Source: Genentech; April 17, 2017.