4555 - Safety and efficacy results of the combination of DPX-Survivac, pembrolizumab and intermittent low dose cyclophosphamide (CPA) in subjects with advanced and metastatic solid tumors: preliminary results from the hepatocellular carcinoma (HCC), NSCLC, bladder cancer, & MSI-H cohorts

Background

DPX-Survivac is a novel T cell activating therapy that has been shown to elicit a strong and prolonged immune response against tumors expressing survivin and correlated with clinical benefits in ovarian cancer. The survivin specific T cells activated by DPX-Survivac, in combination with CPA, are infiltrating the tumors and lead to clinical responses. In preclinical studies, treatment with DPX-Survivac has shown to increase the PD-L1 and PD-1 expression. Pembrolizumab is a potent humanized IgG4 monoclonal antibody with high specificity of binding to the programmed cell death 1 (PD-1) receptor, thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and 2 (PD-L2). This study investigates if a synergistic effect leading to enhanced clinical benefits for the subjects can be achieved with the combination of the checkpoint inhibitor pembrolizumab and the T cell activation therapy, DPX-Survivac, with CPA in subjects with solid tumors.

Methods

This basket trial recruits in ovarian cancer, HCC, NSCLC, bladder cancer and MSI-H tumors. Subjects from all cohorts receive DPX-Survivac and pembrolizumab with intermittent low dose CPA. Subjects are treated for up to 35 cycles of pembrolizumab or confirmed progression, whichever occurs first. The primary objectives are to determine the objective response rate (ORR) by RECIST 1.1 and the safety profile. Secondary objectives include duration of response, disease control rate, progression free survival (PFS), and overall survival (OS). Exploratory analyses will look at the T cell responses and infiltration of the tumor along with biomarker analysis.

Results

The lead-in safety assessment is complete with no modification to the dosing regimen. Preliminary data from the HCC, NSCLC, bladder cancer, and MSI-H cohorts are reported including ORR and safety as well as T cell responses and T cell infiltration.

Conclusions

No safety concerns have been observed with the combination therapy which is showing early signs of clinical efficacy. Enrollment is expected to continue to Stage 2 of the Simon 2 stage design.

Clinical trial identification

NCT03836352.

Editorial acknowledgement

Legal entity responsible for the study

IMV Inc.

Funding

IMV Inc.

Disclosure

L.D. MacDonald: Shareholder / Stockholder / Stock options, Full / Part-time employment: IMV Inc. S. Fiset: Shareholder / Stockholder / Stock options, Full / Part-time employment: IMV Inc. Y.M. Bramhecha: Shareholder / Stockholder / Stock options, Full / Part-time employment: IMV Inc. M. Chaney: Full / Part-time employment: Merck & Co. G.N. Rosu: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: IMV Inc. All other authors have declared no conflicts of interest.