Phase 1 Trial Enrolling Advanced, Castration-resistent Patients to Test Triple Immunotherapy Combo

A Phase 1 trial is enrolling people with metastatic castration-resistant prostate cancer (mCRPC) to test Inovio Pharmaceutical‘s immunotherapy INO-5151 in combination with two other immunotherapies — Celldex’s CDX-301 and Bristol-Myers Squibb’s Opdivo (nivolumab).

The PORTER study (NCT03835533) will include 45 patients who were previously treated with second-generation androgen receptor inhibitors (a kind of hormone therapy), such as Zytiga (abiraterone acetate), Xtandi (enzalutamide), or Erleada (apalutamide).

The trial, a collaboration between Inovio, the Parker Institute for Cancer Immunotherapy (PICI), and the Cancer Research Institute (CRI), will be conducted at clinical sites in California and New York. For more information, click here.

PORTER’s main goal is to determine the triple combination’s safety as measured by the incidence of adverse events. Secondary measures include response rate, overall survival, time to disease worsening or death, and biomarkers of immune activity.

INO-5151 is a combined formulation of Inovio’s INO-5150 and INO-9012, two DNA-based immunotherapies, the company announced. INO-5150 is a kind of cancer vaccine that delivers a piece of DNA coding for the prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA), two proteins present at high levels in prostate cancer cells, helping the body recognize the cells as foreign. INO-9012 codes for interleukin-12 (IL-12), a molecule that further activates the immune system to eliminate the cancer cells.

CDX-301 targets a protein called FLT3 found on the surface of several immune cells, especially dendritic cells. The therapy increases the number of dendritic cells and their mobilization to participate in an immune response.

Opdivo is an immune checkpoint inhibitor that prevents the binding of the PD-L1 protein on cancer cells to the PD-1 protein on immune cells, stopping the cancer from evading immune responses. Opdivo is approved for multiple solid cancers, including melanoma and lung cancer, but its efficacy as a monotherapy in prostate cancer has been limited.

“Inovio is pleased that PICI selected our novel DNA-based immunotherapies to join in this unique combination trial targeting a major unmet medical need. This study demonstrates how Inovio is working with top cancer immunotherapy pioneers to investigate the potential significance of Inovio’s T cell activating immunotherapy in an innovative immuno-oncology combination regimen,” Joseph Kim, president and CEO of Inovio, said in a press release.

The study, which may add a second and expanded phase if initial results support such an addition, is set to fully conclude in March 2023. Its researchers will also be evaluating potential biomarkers of immune activity and patient outcomes.