The approval comes following phase 2 results of 119 patients who participated in the IMvigor210 study.
The FDA has granted accelerated approval to the immunotherapy agent atezolizumab (Tecentriq), a programmed death ligand-1 (PD-L1) inhibitor, for use as first-line in patients with locally advanced or metastatic urothelial carcinoma (mUC) who are ineligible for cisplatin chemotherapy.
The drug was first approved for advanced mUC about a year ago, but use was restricted in patients who had progressed on platinum-based chemotherapy or in the adjuvant and neoadjuvant setting. The current approval is based on phase 2 results from cohort 1 of the IMvigor210 trial, an open-label, single-arm study that evaluated atezolizumab in patients with locally advanced or mUC who were ineligible for cisplatin-containing chemotherapy and were either treatment-naïve or whose disease had progressed at least 1 year after neoadjuvant or adjuvant chemotherapy.
Patients were administered 1200 mg atezolizumab once in 3 weeks or until unacceptable toxicity or disease progression, irrespective of PD-L1 expression. The primary trial endpoint was overall response rate (ORR). Secondary endpoints included duration of response (DoR), overall survival, progression-free survival, and safety.
Of the 119 participants in cohort 1, 28 were confirmed responders, as assessed by an independent review facility; tumors of 9 of the 28 had at least 5% PD-L1 expression. ORR was 23.5% (95% CI, 16.2-32.2) across the cohort, 21.8% (95% CI, 13.7-32.0) in patients with less than 5% PD-L1 expression, and 28.1% (95% CI, 13.8-46.8) in patients with at least 5% PD-L1 expression. Complete response was 6.7% in the overall population and a median DoR has not been reached.
The most common grade 3/4 adverse events observed in the trial included fatigue (8%), urinary tract infection (5%), anemia (7%), diarrhea (5%), increased blood creatinine (5%), increased levels of alanine transaminase (4%), hyponatremia (15%), decreased appetite (3%), and back/neck pain (3%). Five patients discontinued treatment due to adverse events.
“Tecentriq was the first cancer immunotherapy approved by the FDA for people with advanced bladder cancer and has become a standard of care in those whose disease has progressed after receiving other medicines, either before or after surgery, or after their disease has spread,” said Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech, which has developed the drug.
In addition to bladder cancer, atezolizumab is also approved for use in patients with metastatic non-small cell lung cancer who have progressed on platinum-based chemotherapy.