INO-5150 in early treatment of biochemically recurrent prostate cancer

In 2015, Inovio Pharmaceuticals started a Phase I trial of INO-5150 — a new type of immunotherapy using a DNA vaccine for prostate cancer which targets both prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSMA).

At the recent ESMO meeting in Madrid, Spain, Shore et al. presented the results of this study. The following data come from a report by Zachary Klaassen, MD, on the UroToday web site and a media release from  Inovio Pharmaceuticals.

The objective of the study was to assess the safety and immunogenicity of INO-5150 (PSA and PSMA) ± INO-9012 (interleukin-12 or IL-12) in men with biochemically recurrent prostate cancer. The study was an open-label, multi-center, Phase I trial, carried out in 61 men with

  • A rising PSA after surgery and/or radiotherapy
  • A PSA doubling time > 3 months
  • A testosterone level > 150 ng/dl
  • No concomitant androgen deprivation therapy (ADT)
  • No evidence of metastatic disease

The men were randomized to treatment in four slightly different ways:

  • 2.0 mg INO-5150 (Arm A)
  • 8.5 mg INO-5150 (Arm B)
  • 2.0 mg INO-5150 + 1.0 mg INO-9012 (Arm C)
  • 8.5 mg INO-5150 + 1.0 mg INO-9012 (Arm D)

Each form of treatment was administered in four intramuscular doses (on Day 0, and then at weeks 3, 12 and 24), followed by electroporation. (Electroporation is a microbiological technique in which an electrical field is applied to increase the permeability of the cell membrane, allowing chemicals, drugs, or DNA to be introduced into the cell tissues.) The patients were then followed for a total of 72 weeks or roughly 17 months.

Here are the results reported by Shore and his colleagues:

  • Baseline data for the 61 patients treated were as follows:
    • Average (median) age was 69.5 years (range, 55 to 88 years).
    • Average (median) Gleason score was 7 (range, 5 to 10).
    • Average (median) time since diagnosis was 8.4 years (range, 0.4 to 23.8 years).
    • 38/61 patients (62 percent) had a PSA doubling time ≤ 12 months at Day 0.
    • 23/61 patients (38 percent) had  a PSA doubling time > 12 months at Day 0.
  • Flow cytometry revealed
    • Antigen-specific upregulation of CD38 and Perforin on CD8+ T cells in 19/50 patients (38 percent) across the entire trial.
    • This effect was greatest in men in Arm A of the trial (n = 8/14; 57 percent).
  •  For 8/15 patients (53 percent) in Arm A of the trial with PSA doubling times ≤ 12 months, average (median) PSA doubling times were
    • 6.2 (range, 2.9 to 10.2) months at Day 0
    • 19.2 (range, 6.6 to 100.0) months at week 27
  • Seven Grade 3 adverse events were reported in %e patients.
  • No Grade 4 or 5 adverse events reported.
  • Most adverse events were Grade 1 to 3 (in 82 percent of patients).
  • The majority of the Grade 1 to 3 adverse events were associated with injection site reactions.

The authors concluded that:

  • INO-5150 ± INO-9012 was safe at the dosages examined.
  • PSA and PSMA are both immunogenic.
  • INO-5150 induced cellular immune responses.

The authors further concluded that

  • The patients in Arm A showed the highest level of immunological response
  • The patients in Arm A with a baseline PSA doubling time of ≤ 12 months also showed improvements in PSA doubling times.

These results are definitely interesting. However, design and implementation of a Phase III clinical trial to “prove” the efficacy and safety of INO-5150 could be expensive and challenging. We will need to wait to see whether Inovio Pharmaceuticals can raise the money to implement such a trial.

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