1367Tip IMPRINTER: an Open Label, Multi-Center, Dose Escalation/expansion, Phase I Study of IMU-201 (Pd1-Vaxx), a B-cell Immunotherapy, in Adults with Non-Small Cell Lung Cancer

Therapies with monoclonal antibodies targeting PD-1 and its ligands are associated with remarkable outcomes in various cancers and, together with antibodies targeting CTLA-4, have revolutionized cancer treatment (Honey 2017). Some patients treated with PD-1/PD-L1 blockade may develop a primary or secondary resistance” to therapy (Sharma, Hu-Lieskovan et al. 2017). The hypothesis is that a polyclonal induced B-cell antibody response will be more effective or as effective with improved safety over current monoclonal antibody therapy. IMU-201 is being developed using an active immunization approach to treat cancers that overexpress programmed cell death ligand 1 (PD-L1) by inducing the production of anti-PD-1 antibodies through immunization of patients with a peptide epitope designed to stimulate polyclonal antibodies against PD-1 (Kaumaya et al. 2020). The IMPRINTER study is an open-label dose escalation/dose expansion study of IMU-201 as monotherapy treatment for PD-L1 expressing lung cancer, to evaluate safety, tolerability, and immunogenicity and assess the optimum biological dose (OBD) of IMU-201 to be used for further clinical development. All patients enrolled in the study must have previously received an immune checkpoint inhibitor for their underlying cancer and experienced disease progression. Between 12-22 patients will receive 3 doses of either 10 μg/dose, 50 μg/dose, or 100 μg/dose IMU-201 administered as PD1-Vaxx with Montanide ISA 720 VG adjuvant by intramuscular (IM) injection in the deltoid muscle prior to dose-limiting toxicity (DLT) assessment after 29 days on treatment. Dosing will occur on Day 1, Day 15, and Day 29. At Day 43, tumor progression is evaluated. Patients deriving clinical benefit, will continue treatment at Day 64 and every subsequent 63 days. Values and changes in humoral and cellular immunogenicity data including IMU-201 and PD-1 specific antibodies (IgG, IgM), vaccine-specific cytokine levels, and regulatory and effector T and B cells will be evaluated. The study has completed the second dose cohort and enrollment of the third cohort is scheduled. NCT04432207. Imugene Limited. Imugene Limited.