Now Enrolling: The CLEAR research study is testing a new treatment combination for patients with operable non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, making up about 87% of all cases. Treatment depends on the cancer’s stage, and can involve surgery, chemotherapy, immunotherapy, targeted therapy, and/or radiation. For patients with stage 2 to stage 3B disease whose cancer is operable (able to be removed by surgery), the most common approach is chemotherapy and immunotherapy, followed by surgery, and then additional immunotherapy. Unfortunately, even after these multiple treatments, lung cancer often remains or recurs (comes back). These patients need better options to improve their survival and lower the risk of recurrence.

At the time of surgery, pathologists can check to see how well the initial treatment worked by looking for any remaining cancer cells in the tissue samples that are removed. If the treatment has effectively eliminated all detectable cancer, the patient has what is called a pathologic complete response (pCR). However, most patients with stage 2 to stage 3B NSCLC do not have a pCR, which means some cancer cells are still present. These patients face a high risk of their cancer remaining or coming back, even after post-surgical treatment with immunotherapy. To try and improve results for these patients, researchers have designed a new clinical trial called EA5231/CLEAR.

EA5231/CLEAR is testing what happens when a drug called ceralasertib (sir-AL-a-SIR-tib) is added to the usual immunotherapy drug patients take after surgery. The usual drug is an immune checkpoint inhibitor called durvalumab (dur-VAL-yoo-mab), and it is approved by the US Food and Drug Administration for operable NSCLC. Several studies in advanced NSCLC have shown good results when durvalumab is given together with ceralasertib, a targeted cancer therapy. Researchers believe that ceralasertib may make the durvalumab more effective. Researchers hope the combination will also benefit patients with stage 2 to stage 3B NSCLC. They will look to see if the combination of the two drugs helps control cancer for a longer period of time than durvalumab alone.

Patients are eligible for the CLEAR study if they have been diagnosed with stage 2 to select stage 3B NSCLC. Their cancer must not have EGFR or ALK gene mutations, confirmed by tumor testing. Patients must have received or be planning to receive the usual pre-surgery chemotherapy and immunotherapy, followed by surgery. Their doctor must confirm that they have not had a pCR.

Approximately 630 patients will take part in the CLEAR study. After surgery, participants will be randomly assigned by a computer to receive either durvalumab (the usual approach) or durvalumab and ceralasertib. Durvalumab is given intravenously (through a vein in the arm) once per treatment cycle (once every four weeks). Ceralasertib is a pill to be taken orally, twice daily, on days 1-7 of each treatment cycle. Patients in both groups will take their assigned treatment for one year, and all patients will be followed by their doctor for up to 10 years.

This study is led by Dwight Owen, MD, MSc, of The Ohio State University Comprehensive Cancer Center.

Learn more about the EA5231/CLEAR study at ecog-acrin.org.