This phase 2 trial will investigate the safety and effectiveness of different treatment combinations containing durvalumab (Imfinzi) in non-small cell lung cancer (NSCLC).
The main outcome will be the objective response rate (ORR).
Non-small cell lung cancer (NSCLC) is a common form of lung cancer. It is often diagnosed at advanced stages. There are limited treatment options for advanced NSCLC. Immune checkpoint inhibitors (ICIs) are a new type of cancer treatment. Durvalumab is a type of ICI. Cancer cells can manipulate proteins and receptors that prevent the immune system from killing them. ICIs stop this and allow the immune system to kill cancer cells. ICIs are the only option for advanced NSCLC. Some patients do not respond to ICIs. It is important to investigate other treatment combinations for advanced NSCLC.
This trial will investigate the safety and effectiveness of different treatment combinations containing durvalumab in NSCLC. The main outcome will be the ORR.
Who are they looking for?
This study will recruit 260 patients with advanced NSCLC. Participants must be previously treated with ICIs. Patients must have been treated with anti-PD1/PD-L1 ICIs. Female patients must not be pregnant and should agree to use birth control during the study.
Patients cannot take part in the trial if they have mutations (abnormalities) in the following genes – EGFR, ALK, ROS1, BRAF, MET or RET. Other exclusion criteria are a history of autoimmune or inflammatory disorders, brain metastases (tumors), ongoing chemo- or immunotherapy, active infections including B, C hepatitis, HIV.
How will it work
Patients will be assigned to a treatment regimen. There are 5 regimens in the trial. Each group will continue treatment with durvalumab (PD-L1 inhibitor). Group 1 will also receive olaparib (Lynparza; PARP inhibitor). Group 2 will also receive AZD9150 (STAT3 inhibitor). Group 3 will also receive AZD6738 (ATR inhibitor). Group 4 will also receive vistusertib (mTOR inhibitor). Group 5 will also receive oleclumab (CD73 inhibitor). Treatment will last up to 3.5 years if well tolerated.
The main outcome will be the ORR at 12 weeks. Overall survival will also be measured up to 4.5 years.