Type of information: Positive opinion for the granting of a Market Authorisation in the EU
Product name: Tecentriq® - MPDL3280A - atezolizumab
Therapeutic area: Cancer - Oncology
Action mechanism: immunotherapy product/immune checkpoint inhibitor/monoclonal antibody. Anti-PDL1 antibody MPDL3280A is a monoclonal antibody designed to make cancer cells more vulnerable to the body’s immune system by interfering with a protein called PD-L1. PD-L1 is found on the surface of cells in tumours and is believed to act as a “stop sign,” preventing the immune system from destroying cancer cells. By inhibiting PD-L1, MPDL3280A may enable the activation of T cells, restoring their ability to effectively detect and attack tumour cells.
Company: Genentech (USA), a member of Roche Group (Switzerland)
Disease: metastatic bladder cancer
- • On July 20, 2017, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Tecentriq® for the treatment of locally advanced or metastatic urothelial carcinoma. Tecentriq® will be available as a 1200 mg concentrate for solution for infusion. The benefit of Tecentriq® is its ability to show durable responses in first-line cisplatin-ineligible and secondline
- The most common side effects are fatigue, decreased appetite, nausea, dyspnoea, diarrhoea, rash, pyrexia, vomiting, arthralgia, asthenia and pruritus. Tecentriq is also associated with immune-related adverse reactions including pneumonitis, hepatitis, colitis, hypothyroidism or hyperthyroidism, adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, Guillain-Barré syndrome, meningoencephalitis and pancreatitis.
The full indication is: "Tecentriq® as monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma (UC) after prior platinum-containing chemotherapy or who are considered
- • On April 18, 2017, Roche announced that the FDA granted accelerated approval to 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). The approval is based on the Phase II IMvigor210 study. This is the third approval for Tecentriq® in under a year in the US. The antibody 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.
- • On January 9, 2017, Roche announced that the FDA has accepted the company’s supplemental Biologics License Application (sBLA) and granted Priority Review for Tecentriq® (atezolizumab) for the treatment of people with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin chemotherapy, and are either previously untreated or have disease progression at least 12 months after receiving chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant). This sBLA submission for Tecentriq® is based on results from the Phase II IMvigor210 study, and the FDA will make a decision on approval by 30 April 2017.
- • On May 18, 2016, the FDA approved Tecentriq® (atezolizumab) to treat urothelial carcinoma. The antibody is approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma whose disease has worsened during or following platinum-containing chemotherapy, or within 12 months of receiving platinum-containing chemotherapy, either before (neoadjuvant) or after (adjuvant) surgical treatment.
- The safety and efficacy of Tecentriq® were studied in a single-arm clinical trial involving 310 patients with locally advanced or metastatic urothelial carcinoma. This trial measured the percentage of patients who experienced complete or partial shrinkage of their tumors (objective response rate). The study also looked at the difference in effect based on “positive” versus “negative” expression of the PD-L1 protein on patients’ tumor-infiltrating immune cells. In all patients, 14.8 percent of participants experienced at least a partial shrinkage of their tumors, an effect that lasted from more than 2.1 to more than 13.8 months at the time of the response analysis. In patients who were classified as “positive” for PD-L1 expression, 26 percent of participants experienced a tumor response (compared to 9.5 percent of participants who were classified as “negative” for PD-L1 expression).
- While patients who received Tecentriq® experienced a tumor response across the study, the greater effect in those who were classified as “positive” for PD-L1 expression suggests that the level of PD-L1 expression in tumor-infiltrating immune cells may help identify patients who are more likely to respond to treatment with Tecentriq®. Therefore, the FDA also approved the Ventana PD-L1 (SP142) assay to detect PD-L1 protein expression levels on patients’ tumor-infiltrating immune cells and help physicians determine which patients may benefit most from treatment with Tecentriq®.
- The most common side effects of treatment with Tecentriq® were fatigue, decreased appetite, nausea, urinary tract infection, fever (pyrexia) and constipation. Tecentriq also has the potential to cause infection and serious side effects that result from the immune system effect of Tecentriq (known as “immune-mediated side effects”). These severe immune-mediated side effects involve healthy organs, including the lung, colon and endocrine system.
- • On May 31, 2014, Genentech announced that the FDA has granted MPDL3280A Breakthrough Therapy Designation in metastatic bladder cancer.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2016-05-18/2017-04-18
Favourable opinion UE: 2017-07-20
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: