Adenovirus-based Cancer Immunotherapies: ONCOS-102

ONCOS-102 is Targovax’s lead adenovirus-based pipeline product – a purposefully engineered human serotype 5 adenovirus optimized to induce systemic anti-tumor T cell responses in cancer patients.

ONCOS-102 has completed a Phase I clinical study and is being tested in further combination clinical trials in several solid tumor indications:

  • Mesothelioma in combination with standard of care chemotherapy (enrolling patients)

  • Melanoma in combination with an immune checkpoint inhibitor (enrolling patients)

  • Ovarian cancer in combination with an immune checkpoint inhibitor (planned study)

  • Prostate cancer in combination with a dendritic cell vaccine (planned study)

ONCOS-102 showed encouraging Phase I efficacy data in a challenging patient population. In its Phase I clinical trial in heavily-pretreated patients with multiple types of solid tumors, ONCOS-102 demonstrated a stable disease (SD) rate of 40% in 10 evaluable patients.

  • Patient-level data demonstrate multiple immunotherapeutic mechanisms. The Phase I data showed a dramatic increase in tumor-infiltrating cytotoxic CD8+ T cells, innate immune system activation, and cancer specific CD8+ T-cells in blood indicating systemic activation of the immune system. Both the increase of innate immune cell infiltration and the increase of CD8+ T cells were correlated with overall survival.

  • Clean safety database in over 100 patients. A five-year compassionate use program has demonstrated an encouraging safety profile in 115 ONCOS-102 treated patients. Adverse events were mostly of grade 1 or 2. The ONCOS-102 Phase I study did not identify a dose-limiting toxicity.

  • Synergistic potential in combination usage. Preclinical data has shown synergistic effects between ONCOS-102 and chemotherapy (doxorubicin/ifosfamide). There is also compelling mechanistic rationale for combining ONCOS-102 with immune checkpoint inhibitors, which would benefit from ONCOS-102’s innate immune system activation, co-stimulatory effects and T cell activation, yielding a complete immunotherapeutic arsenal.

More on the mechanism of action of ONCOS-102

Magnus Jaderberg picture

Magnus Jaderberg
Chief Medical Officer, Head of Research & Development

We aim to develop ONCOS-102 in combination with standard of care chemotherapeutics in selected cancer indications. Combining ONCOS-102 with immune checkpoint inhibitors is also an intriguing opportunity which we are actively exploring.

Future development of Targovax’s Oncos oncolytic virus platform:

  • To start up 4 combination clinical trials with ONCOS-102 during 2017:

    • Phase Ib/II in mesothelioma, in combination with standard of care chemotherapy (trial started in June 2016, first patient dosed, recruitment ongoing)
    • Phase Ib in immune checkpoint refractory melanoma, in combination with an immune checkpoint inhibitor
    • Phase I/II in ovarian cancer, in combination with an immune checkpoint inhibitor
    • Phase I in prostate cancer, in combination with a dendritic cell vaccine
  • To continue a combination clinical trial of TG02, in combination with the immune checkpoint inhibitor Keytruda, in colorectal cancer.
  • To move follow-on candidates into clinical trials and to develop virus constructs with novel transgenes
  • To explore synergies between Targovax’s Oncos and TG technology platforms

The Targovax team has significant experience in developing and manufacturing adenoviral constructs for clinical use.

Lukasz picture

Lukasz Kuryk
Senior Research Scientist

We have demonstrated that ONCOS-102 treatment can reinstate the immune system’s capacity to recognize and attack cancer cells, even in late stage cancer patients with low immunogenic tumor types.

When the development is completed, we will have an efficient discovery platform covering the whole path from construct design to clinical manufacturing using commercially validated methods. The Targovax platform provides unparalleled efficacy for taking constructs with novel engineered characteristics from sketch board to clinical development. When compared with the development of new antibodies, this Targovax discovery platform is much more time- and cost-effective.