Abstract 132TiP
Background
Unresectable stage 3 non-small cell lung cancer is treated with chemoradiation followed by consolidation durvalumab since early 2018. However, the updated 5-year survival from the PACIFIC study showed a OS of 42.9% vs 33.4% and PFS of 33.1% vs 19% when compared with the placebo. Patients treated with durvalumab had 28% less chance to die within 5 years. There is still a lot of room to improve. Tregs participate in anti-tumor immunity leading to immune evasion. We hypothesize that Tregs contributes to immune checkpoint inhibitor resistance and copanlisib boosts immune response in stage III NSCLC on durvalumab.
Trial design
This is a phase Ib clinical trial with a dose finding phase and a dose expansion phase. Primary objective of the study is the safety and tolerability adding copanlisib to durvalumab. The secondary objective includes PFS. Initially 3 patients appropriate for durvalumab consolidation will be enrolled and treated with copanlisib 60 mg intravenously once every two weeks along with durvalumab 1500 mg IV every 4 weeks. If no more than one dose limiting toxicity is observed in 28 days, another 3 will be treated. If 2 or less out of 6 patients experience DLT, the trial will proceed with the above dosing schedule in the dose expansion phase enrolling 6–12 patients. Treatment with both drugs will continue until disease progression, intolerance or at the end of one year whichever comes first. Patients aged 18–80 year will be enrolled when they do not have disease progression following concurrent chemoradiation for stage 3 disease appropriate for durvalumab consolidation. Patients need minimal organ functional reserve for bone marrow, liver and kidney function. Hepatitis or HIV infection patients are eligible if the infection is under control. Heart function cut off is NYHA class IIb or better. Known driver mutation-positive patients (EGFR, ALK) are excluded so is autoimmune disease on active immunosuppressant, organ transplant status. Hypertension not controlled well (above 150/90) or poorly controlled diabetes (HbA1c.8.5) are excluded. Patients are not allowed to take strong CYP3A4/5 inhibitor or QT prolongation agents. Currently, 4 patients are enrolled.
Clinical trial identification
NCT 04895579 First release May 21, 2021.
Legal entity responsible for the study
University of Kentucky, Markey Cancer Center.
Funding
Markey Cancer Center.
Disclosure
Z. Hao: Non-Financial Interests, Institutional, Funding, study drug: Bayer Inc.