The US Food and Drug Administration (FDA) granted accelerated approval to Roche's Tecentriq (atezolizumab) for the treatment of people with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin chemotherapy. Tecentriq was previously approved for people with locally advanced or mUC who have disease progression during or following any platinum-containing chemotherapy, or within 12 months of receiving chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant). Bladder cancer is the most common type of urothelial carcinoma, and up to half of all people with the advanced form of the disease are unable to receive cisplatin chemotherapy as an initial treatment and therefore have a high unmet medical need. Urothelial carcinoma also includes cancers of the urethra, ureters and renal pelvis.
“We are pleased that Tecentriq will now be available to more people with advanced bladder cancer, including those who are unable to receive initial treatment with a standard chemotherapy”, said Sandra Horning, MD, chief medical officer and head of global product development. “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.”
The FDA’s Accelerated Approval Programme allows conditional approval of a medicine that fills an unmet medical need for a serious condition, based on early evidence suggesting clinical benefit. The indication for Tecentriq is approved under accelerated approval based on tumour response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Today’s approval of Tecentriq is based on the phase II IMvigor210 study.
This is the third approval for Tecentriq in under a year in the US. Tecentriq is also approved for the treatment of people 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 tumour has EGFR or ALK gene abnormalities.
IMvigor210 is an open-label, multicentre, single-arm phase II study that evaluated the safety and efficacy of Tecentriq in people with locally advanced or metastatic urothelial carcinoma (mUC), regardless of PD-L1 expression. People in the study were enrolled into one of two cohorts. This accelerated approval is based on results from Cohort 1, which consisted of 119 people 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. People in this cohort received a 1200-mg intravenous dose of Tecentriq every three weeks until either unacceptable toxicity or disease progression. The primary endpoint of the study was objective response rate (ORR).
A summary of the efficacy data from the IMvigor210 study that supports this accelerated approval is included below.
The most common Grade 3–4 adverse reactions (= 2%) were: fatigue (8%), urinary tract infection (5%), anaemia (7%), diarrhoea (5%), increase in the level of creatinine in the blood (5%), intestinal obstruction (partial or complete blockage of the bowel), increase of the liver enzyme alanine transaminase (4%), hyponatraemia (low blood sodium level; 15%), decreased appetite (3%), sepsis (blood infection), back/neck pain (3%), renal failure and hypotension (low blood pressure). Five people (4.2%) experienced either sepsis, cardiac arrest, myocardial infarction, respiratory failure or respiratory distress, which led to death. Tecentriq was discontinued for adverse reactions in 4.2% of the 119 patients.
Roche is evaluating Tecentriq in a confirmatory phase III study (IMvigor211), which compares Tecentriq to chemotherapy as initial treatment in people with a specific type of advanced bladder cancer and in people whose bladder cancer has progressed on at least one prior platinum-containing regimen.