A Multicentre Randomised Phase III Trial Comparing Atezolizumab Plus Bevacizumab and Standard Chemotherapy Versus Bevacizumab and Standard Chemotherapy as First-line Treatment for Advanced Malignant Pleural Mesothelioma

Brief Summary

Detailed Description

Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer arising from the mesothelial surface of the pleura. In Europe, the incidence is about 20 per million and is almost always caused by asbestos exposure, with a usual lag time of 30 years between exposure and presentation. Patients diagnosed with advanced MPM have limited treatment options, representing a strict unmet need. Despite decades of clinical research, cytotoxic chemotherapy remains one of the few therapeutic options that has been proven to improve survival in advanced MPM in a randomised controlled trial. The combination of cisplatin and pemetrexed has become standard first-line therapy worldwide for patients who are not suitable for aggressive surgery or in whom chemotherapy is recommended as part of a multimodality regimen. Carboplatin is often substituted for cisplatin, due to simpler and shorter administration and assumption of a more favourable toxicity profile based on experience in other diseases. Patients with MPM have limited treatment options, representing a strict unmet need. An antibody is a common type of protein usually made in the body in response to a foreign substance. Antibodies attack foreign substances and protect against infection. The two monoclonal antibodies (atezolizumab and bevacizumab) used in this trial are laboratory-produced antibodies. Atezolizumab is engineered to attach to immune cells to stimulate their activity against cancer cells. Atezolizumab and bevacizumab are both approved by the European Medicines Agency for the treatment of lung and other cancers. The addition of atezolizumab to bevacizumab plus standard chemotherapy for the treatment of MPM is being investigated in this trial. All participants will receive 4-6 cycles of standard chemotherapy consisting of carboplatin AUC 5 (area under the plasma concentration versus time curve) plus pemetrexed 500mg/m\^2 given intravenously, on day 1 of every 3 week cycle for about 12 to 18 weeks. Participants will be randomly assigned to one of two treatment groups: Treatment 1 * Bevacizumab 15 mg/kg intravenously on day 1 of every 3-week cycle, plus * 4-6 cycles of chemotherapy OR Treatment 2 * Atezolizumab 1200 mg fixed dose intravenously on day 1 of every 3-week cycle, plus * Bevacizumab 15 mg/kg, intravenously on day 1 of every 3-week cycle, plus * 4-6 cycles of chemotherapy Participants will continue to receive treatment until disease progression, or until treatment is stopped at the request of the participant or treating doctor, or the participant withdraws consent. A total of 400 participants from approximately 45 centres in Europe are expected to be included in this trial which will take approximately 6 years to be completed after the first participant is enrolled.

Primary Outcomes

Secondary Outcomes

• Objective Response Rate (ORR)(From start of protocol treatment acorss all time-points until end of protocol treatment or, as an alternative approach, until the end of follow-up, assessed up to 58 months)
• Progression-free Survival (PFS) according to the mRECIST v1.1(From date of randomisation until documented progression or death, if progression is not documented, assessed up to 58 months)
• Disease Control (DC) at 24 weeks(24 weeks after protocol treatment start)
• Number of participants with treatment related adverse events according to Common Toxicity Criteria for Adverse Events (CTCAE) v5.0(Assessed from the date of informed consent until 90 days after protocol treatment discontinuation. Analysed at 58 months after randomisation of the first patient)
• Time to Treatment Failure (TTF)(From randomisation until discontinuation of protocol treatment for any reason, assessed up to 58 months)
• Duration of Response (DoR)(From date of first documentation of objective response until date of first documented progression/ relapse or death, assessed up to 58 months)