Cha, Steven

e21134 Background: Therapies with monoclonal antibodies targeting PD-1 and its ligands are associated with remarkable outcomes and have revolutionized cancer treatment (Honey 2017). However, patients treated with PD-1/PD-L1 blockade may develop “a primary or secondary resistance” to therapy (Sharma, Hu-Lieskovan et al. 2017). Contrary to monoclonal antibodies, chimeric B-cell cancer vaccines have the advantage of producing polyclonal B-cell antibodies that can potentially induce memory B- and T-cell responses, while reducing immune evasion and suppression. 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 (PD1-Vaxx) is being developed using an active immunization approach to treat cancers that overexpress PD-L1 by inducing the production of anti-PD-1 antibodies with a peptide epitope designed to stimulate polyclonal antibodies against PD-1 (Kaumaya et al. 2020). Methods: The IMPRINTER study is an ongoing open-label dose escalation study of IMU-201 as monotherapy (Phase 1) or in combination with atezolizumab (Phase 1b) for patients with PD-L1 expressing non-small cell lung cancer (NSCLC). All patients enrolled in Phase 1 of the study must have previously received an immune checkpoint inhibitor and experienced disease progression. The primary objective is to evaluate the safety and tolerability of IMU-201 and identify the optimal biological dose (OBD). The secondary objective is to evaluate the efficacy of IMU-201 as monotherapy and in combination with atezolizumab. Humoral and cellular immunogenicity data will be evaluated, including IMU-201 and PD-1 specific antibodies (IgG, IgM), vaccine-specific cytokine levels, and regulatory and effector T and B cells. IMU-201 is administered by intramuscular (IM) injection on Day 1, Day 15, and Day 29. Dose-limiting toxicity (DLT) assessment is completed after 29 days on treatment. Tumor progression is evaluated according to RECIST 1.1 at Day 43 then every 42 days until progression or withdrawal. Results: In Phase 1, four patients were enrolled into each of the three cohorts at 10 μg/dose, 50 μg/dose and 100 μg/dose IMU-201 with no DLTs observed. In the 10 μg/dose cohort, one patient achieved CR and one patient SD; in the 50 μg/dose cohort, four patients achieved SD; and in the 100 μg/dose cohort, one patient achieved PR and two patients achieved SD. Within the 100 μg/dose cohort, one patient experienced an immune related pneumonitis after two IMU-201 administrations and discontinued from study treatment. Conclusions: IMU-201 had no observed DLT and demonstrated preliminary signs of efficacy. The study will therefore move into Phase 1b with IMU-201 being assessed in combination with atezolizumab. Clinical trial information: NCT04432207.

Background: The diagnosis of hypertension requires systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg on at least 2 different occasions. Therefore, there is the possibility of patients with elevated BP remaining undiagnosed if not seen by the same provider. Purpose: To utilize electronic medical records (EMR) to identify patients not previously diagnosed with hypertension that have elevated blood pressure meeting criteria for a diagnosis of hypertension using a threshold of SBP ≥ 140mmHg or DBP ≥ 90 mmHg (high BP) on 2 or more occasions. Methods: This was a cross sectional design utilizing retrospective multi-year billing and clinical data from a large multi-specialty center in the Midwest. Using electronic records of all outpatient visits in each year from 2009 - 2011, patients with at least 2 visits with SBP ≥ 140mmHg or DBP ≥ 90 mmHg (2HBP) in the measurement year were identified. These patients were compared with previously identified cohorts of known hypertension patients (Known HTN) compiled using the EMR problem list. A sensitivity analysis was done using patients with high BP at 2 consecutive visits (2CHBP) and also those with high BP at 3 consecutive visits (3CHBP). We compared proportions of patients with high BP without a prior diagnosis of hypertension (UDHTN). Results: The proportion of patients with SBP ≥ 140mmHg or DBP ≥ 90 mmHg without a prior diagnosis of hypertension (UDHTN) when compared to the cohort of known patients with a diagnosis of hypertension (Known HTN) was 25% in 2009, 26% in 2010, and 28% in 2011 in the 2CHBP cohort compared to 27% in 2009, 28% in 2010, and 30% in 2011 in the 2HBP cohort and 18% in 2009, 19% in 2010 and 23% in 2011 in the 3CHBP cohort. Conclusion: About a quarter of patients meeting current thresholds on multiple and consecutive visits did not have a known diagnosis of hypertension. The use of EMR can identify these patients for commencement of appropriate management. Table 1