We report a multicenter phase 1b2 study evaluating the combination of Imprime PGG and pembrolizumab in patients with previously treated advanced stage non-small cell lung cancer. These are my disclosures. Imprime is a beta-glucan. It acts as a pathogen-associated molecular pattern and creates critical non-self signals recognized by the innate immune system. It enhances immune cell killing, activation of antigen-presenting cells and T-cells crosstalk. In preclinical studies, Imprime improved the efficacy of immune checkpoint inhibitors in various cancer models. Therefore, we hypothesize that combination of Imprime and pembrolizumab will improve the outcome of advanced stage non-small cell lung cancer. This was a multicenter single arm study consisting of two parts, phase 1b and 2. We enrolled patient with advanced stage non-small cell lung cancer who were previously treated with platinum-based chemotherapy and naive to immune checkpoint inhibitors. After the approval of pembrolizumab in the first line setting, we amended the protocol to allow enrollment of patients who previously progressed on immunotherapy. Objective of the phase 1b was to determine recommended phase 2 dose of Imprime. Primary objective of the phase 2 was to determine progression-free survival of patient who received the combination of Imprime and pembrolizumab. Study schema is shown on the right. The study was powered to detect an improvement in progression-free survival by 3.1 months from the historical control with a required N of 24. We enrolled 35 patients, 9 were recruited to phase 1b and remaining 1 enrolled in phase 2. Two patient withdrew consent, table on the right shows the patient's demographic and disease characteristics. The major difference between the patient population of phase 1b and 2 was the receipt of immune checkpoint inhibitor as their prior lines of therapy. All patients in the phase 1b were naive to immunotherapy, whereas several patients in phase 2 received immune checkpoint inhibitor as their last line of therapy. All patients were included in the safety analysis. No dose limiting toxicity was observed in the phase 1b. Imprime at a dose of 4 mg per kg every 3 week was recommended for the phase 2 study. Treatment related adverse event occurring at a frequency of 5% or higher are shown in the table. Most of these adverse event were related to Imprime. Only 3 serious adverse event were noted and all of these were grade 3. Efficacy outcomes of patients in phase 1b and 2 are shown in the tables. Objective response rate, median progression free and overall survival were better for patients who participated in the phase 1b compared to phase 2 study. This was probably because patients in the phase 1b were naive to immune checkpoint inhibitors. Difference in PD-L1 expression between the two population is another possibility and we are collecting this information. Several correlative studies are being performed at this time and some of these are listed on the slide. In conclusion, the combination of Imprime and Pembrolizumab is safe. Addition of Imprime to Pembrolizumab did not improve patient's outcome. However, several patients in phase 2 were progressed on prior immune checkpoint inhibitor before participating in the study. Outcome of patients in phase 1b were better as all of them were naive to immunotherapy. We thank all the patients and their families who participated in the study. We acknowledge and appreciate the effort of research staff at the participating institutions and the Big Ten Cancer Research Consortium for helping with the study.

Imprime PGG

pembrolizumab

non-small cell lung cancer

beta-glucan

phase 2 study