Date: 2017-09-25
Type of information: Granting of a Market Authorisation in the EU
Product name: Tecentriq® - MPDL3280A
Compound: atezolizumab
Therapeutic area: Cancer - Oncology
Action mechanism:
- immunotherapy product/immune checkpoint inhibitor/monoclonal antibody. Anti-PDL1 antibody MPDL3280A is an investigational 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. MPDL3280A is being studied in clinical trials to understand whether blocking PD-L1 will help the immune system respond to cancer.
Company: Roche (Switzerland)
Disease:
- PD-L1-positive (Programmed Death-Ligand 1) non-small cell lung cancer (NSCLC) whose disease has progressed during or after platinum-based chemotherapy (and appropriate targeted therapy for those with an EGFR mutation-positive or ALK-positive tumour)
Latest news:
- • 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 non-small cell lung cancer (NSCLC). Tecentriq® will be available as a 1200 mg concentrate for solution for infusion. The benefit of Tecentriq® is its ability to improve survival compared with docetaxel in patients previously treated with chemotherapy. 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 non-small cell lung cancer (NSCLC) after prior chemotherapy. Patients with EGFR activating
mutations or ALK-positive tumour mutations should also have received targeted therapy before receiving
Tecentriq®."
- • On October 18, 2016, the FDA approved Tecentriq® (atezolizumab) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose disease progressed during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving atezolizumab. The approval is based on two international, randomized, open-label clinical trials (OAK and POPLAR) that demonstrated consistent results in efficacy and safety in a total of 1137 patients with NSCLC. Compared with docetaxel, treatment with atezolizumab in the intended patient population in the two trials resulted in a 4.2 and a 2.9 month improvement in overall survival (OS), respectively. The median OS in OAK was 13.8 months (95% confidence interval [CI] 11.8,15.7) in the atezolizumab arm compared to 9.6 months (95% CI 8.6,11.2) in the docetaxel arm (hazard ratio [HR]=0.74 [95% CI 0.63,0.87]; p=0.0004). The median OS in POPLAR was 12.6 months (95% CI 9.7, 16.0) and 9.7 months (95% CI 8.6, 12.0) (HR=0.69 [95% CI 0.52, 0.92]) for the atezolizumab and docetaxel arms, respectively.
- The most common (greater than or equal to 20%) adverse reactions in patients in the primary safety analysis population (POPLAR trial) in patients treated with atezolizumab were fatigue, decreased appetite, dyspnea, cough, nausea, musculoskeletal pain, and constipation. The most common (greater than or equal to 2%) grade 3-4 adverse events in patients treated with atezolizumab were dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, AST increase, ALT increase, dysphagia, and arthralgia. Clinically significant immune-related adverse events for patients receiving atezolizumab included pneumonitis, hepatitis, colitis, and thyroid disease. The recommended atezolizumab dose is 1200 mg administered as an intravenous infusion over 60 minutes every three weeks until disease progression or unacceptable toxicity.
- • On February 2, 2015, Roche announced that it has received a second Breakthrough Therapy Designation from the FDA for its investigational cancer immunotherapy MPDL3280A (anti-PDL1). The designation was granted for the treatment of people with PD-L1-positive (Programmed Death-Ligand 1) non-small cell lung cancer (NSCLC) whose disease has progressed during or after platinum-based chemotherapy (and appropriate targeted therapy for those with an EGFR mutation-positive or ALK-positive tumour).
This breakthrough therapy designation is based on early results of MPDL3280A in people whose NSCLC was characterised as PD-L1-positive by an investigational test being developed by Roche. All studies of MPDL3280A are prospectively evaluating PD-L1 expression. Some studies will evaluate the medicine regardless of a tumor’s PD-L1 status; other studies are evaluating the medicine only in people whose tumors are characterized as PD-L1 positive.
The FDA granted the first Breakthrough Therapy Designation for MPDL3280A in metastatic bladder cancer in 2014. Ongoing pivotal studies of MPDL3280A include lung and bladder cancer, and Roche plans to initiate Phase III studies in additional tumor types this year.
Patents:
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: 2016-10-18
UE authorization: 2017-09-25
Favourable opinion UE: 2017-07-20
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes
