BTC clinical trials

INO-5401 and INO-9012 Delivered by Electroporation in Combination with Cemiplimab (REGN2810) in Newly-Diagnosed Glioblastoma

 

Summary

This clinical trial will evaluate the safety and efficacy of INO-5401, INO-9012, and cemiplimab, alongside radiation therapy and temozolomide (TMZ), in treating patients with newly diagnosed glioblastoma.

INO-5401 and INO-9012 are comprised of DNA molecules, or plasmids, and are injected intramuscularly and then delivered using electroporation – a technique using electric pulses to push the DNA plasmids into cells. The cells that are electroporated will begin producing specific molecules based on the instructions in the DNA plasmid. For example, cells electroporated with INO-5401 will begin producing antigens that are common in many cancer cells (including WT1, PSMA, and hTERT). Production of these antigens helps activate T-cells to better recognize cancer cells. INO-5401 is therefore considered a T-cell activating immunotherapy.

INO-9012 is another immunotherapeutic agent, a DNA plasmid encoding the human interleukin-12 (IL-12) gene. Cells electroporated with INO-9012 will begin producing IL-12, a protein that promotes the activation of natural killer cells, among other immune-stimulating effects.

Cemiplimab is an antibody-based immunotherapy, administered intravenously, that also targets the immune system and activates it to stop cancer growth and/or kill cancer cells. More specifically, cemiplimab works by binding and inhibiting PD-1, a protein that normally protects the body from attacking itself. Normally, PD-1 works by detecting a molecular signal (called PDL-1) made by various cells across the body. Some cancer cells take advantage of this protection mechanism making the protective signal themselves. Blocking PD-1 with cemiplimab allows the immune system to activate its T-cells and recognize these tumors as cells to be attacked.

Eligible participants will be separated into two cohorts, depending on MGMT promoter methylation status. Both cohorts will receive the INO-5401, INO-9012, and cemiplimab at the same doses and schedule, in addition to radiation therapy and TMZ, if clinically indicated:

  • Experimental Cohort A (Unmethylated MGMT Promoter): INO-5401 + INO-9012 + Cemiplimab + RT + TMZ
  • Experimental Cohort B (Methylated MGMT Promoter): INO-5401 + INO-9012 + Cemiplimab + RT + TMZ

 

Inclusion Criteria
  1. Newly-diagnosed brain cancer with histopathological diagnosis of GBM
  2. Karnofsky Performance Status (KPS) rating of >/=70 at baseline
  3. Receive dexamethasone equivalent dose </=2 mg per day, stable or decreased for >/= three days prior to Day 0
  4. Recovery from the effects of prior GBM surgery as defined by the Investigator
  5. Electrocardiogram (ECG) with no clinically significant findings as assessed by the Investigator
  6. Adequate organ function as demonstrated by hematological, renal, hepatic laboratory assessments
  7. Agree that during the trial, men will not father a child, and women cannot be or become pregnant. Participants must be of non-child bearing potential or agree to use one highly effective or combined contraceptive methods that result in a failure rate of <1% per year during the treatment period and at least through week 12 after last dose
  8. Ability to tolerate magnetic resonance imaging (MRI).

For the most up-to-date list of criteria, visit clinicaltrials.gov.

Exclusion Criteria
  1. Presence of greater than 1 cm x 1 cm residual tumor enhancement on postoperative MRI
  2. Multifocal disease or leptomeningeal disease (LM) disease on post-operative MRI
  3. Not scheduled to start radiation within 42 days of surgical resection of tumor
  4. Dexamethasone equivalent dose >2 mg per day
  5. Prior treatment with an agent that blocks the PD-1/PD-Ligand 1 pathway
  6. Receipt of previous approved or investigative immune modulatory agent within 28 days of receiving the first dose of treatment
  7. Prior treatment with idelalisib
  8. Past, current or planned treatment with tumor treatment fields; oncolytic viral treatment; or prior exposure to an investigational agent or device within 28 days of receiving the first dose of treatment
  9. Allergy or hypersensitivity to cemiplimab or to any of its excipients
  10. History of documented allergic reactions or acute hypersensitivity reaction attributed to antibody treatments
  11. Ongoing or recent (within 5 years) evidence of autoimmune disease that required treatment with systemic immunosuppressive treatments
  12. Diagnosis of immunodeficiency or treatment with systemic immunosuppressive therapy within 28 days prior to the first dose of trial treatment, other than dexamethasone for the underlying disease under investigation, as noted in the inclusion criteria
  13. History of clinically significant, medically unstable disease which, in the judgment of the investigator, would jeopardize the safety of the subject, interfere with trial assessments or endpoint evaluation, or otherwise impact the validity of the trial results.

For the most up-to-date list of criteria, visit clinicaltrials.gov.

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