Trial Testing Triple Combo Immunotherapy in Newly-diagnosed Glioblastoma Completes Patient Enrollment

A Phase 1/2 clinical trial testing a triple immunotherapy combination for newly diagnosed glioblastoma has completed patient enrollment three months ahead of schedule.

Inovio Pharmaceuticals, the company leading the trial, announced the trial (NCT03491683) has enrolled the planned 52 participants at centers across the U.S. The trial is exploring Inovio’s T-cell activating therapies INO-5401 and INO-9012, in combination with cemiplimab, a PD-1 inhibitor developed by Regeneron Pharmaceuticals and Sanofi.

Glioblastoma is the most common and deadliest type of brain cancer, with fewer than 5% of patients living more than five years after their diagnosis. While immune checkpoint inhibitors have shown promise in many cancers, results in glioblastoma haven’t been encouraging.

Inovio is testing whether INO-5401 and INO-9012 — two immunotherapies meant to boost T-cell activity against cancer cells — could be used in combination with an immune checkpoint inhibitor with better results than treatment with a checkpoint inhibitor only.

INO-5401 is an immunotherapy that encodes the antigens for the WT1, hTERT, and PSMA proteins found at high levels in several cancer cell types, but minimally expressed in healthy tissues.

While INO-5401 encodes for cancer proteins, INO-9012 encodes for the interleukin-12 (IL-12) protein, which triggers the activation and expansion of immune T-cells, boosting the anti-cancer immune response.

The ongoing Phase 1/2 trial is testing these experimental immunotherapies along with the immune checkpoint inhibitor cemiplimab — approved as Libtayo for a type of skin cancer — in newly-diagnosed glioblastoma patients who had surgery to remove their tumor.

In the trial, participants will receive INO-5401 and INO-9012, delivered into the muscle every three weeks for the first four doses, and then every nine weeks until disease progression, study withdrawal, severe toxicity, or death. Cemiplimab will be given every three weeks via an intravenous injection.

Patients also may receive radiation and the chemotherapy temozolomide, if needed.

The study’s main goal is to assess the combination’s safety, measured as the percentage of patients experiencing adverse side effects. Secondary measures include overall survival at 18 months and immune assessments aiming to determine if the treatment induces an immune response to cancer.

“In this GBM trial, our goal is to increase the overall survival of patients facing a disease where neither the standard of care, nor clinical outcomes have changed in a clinically significant way in more than a decade,” J. Joseph Kim, Inovio’s president and CEO, said in a press release.

Details from the trial were revealed April 1 at the American Association for Cancer Research (AACR) Annual Meeting, in Atlanta, Georgia, in the presentation, “INO-5401 and INO-9012 delivered by electroporation (EP) in combination with cemiplimab (REGN2810) in newly-diagnosed glioblastoma (GBM) (NCT03491683).”

“We sincerely thank the patients and their doctors for participating in our innovative combination trial. This is an important step for Inovio’s cancer combination strategy using our T cell-generating therapies in combination with PD-1/PD-L1 inhibitors for [glioblastoma] and for multiple other cancers to improve overall efficacy of immunotherapy,” said Kim.