The ONCOS-102 technology is based on a genetically engineered AdV5 adenovirus system designed to selectively infect and destroy tumor cells and drive a patient-specific anti-tumor immune response.
ONCOS-102 is designed to activate the immune system by:
- Priming tumor-specific T-cells through powerful co-stimulation
- Counteracting immune-suppressive mechanisms in the tumor microenvironment (TME)
- Co-expression of the powerful cytokine GM-CSF from a genetic cassette insert
PD-1 Checkpoint Inhibitor (CPI) refractory advanced melanoma
PD-1 CPI refractory advanced melanoma is a major unmet medical need affecting up to 25,000 patients per year globally in the major markets. The diagnosis is associated with a poor prognosis and at this stage of the disease there are limited treatment options available.
In a phase 1 trial, ONCOS-102 in combination with a PD-1 CPI demonstrated a highly competitive response rate (ORR) of 35% in this patient population. Importantly, the strong ORR outcome was corroborated by shrinkage of non-injected lesions and biomarker data showing significant increase in T-cell infiltration and broad and persistent activation of immune-related gene signatures in responding patients.
Phase 2 multi-cohort trial
Based on these promising early clinical results, Targovax is planning to conduct a larger, phase 2 study to further explore and demonstrate the benefit of ONCOS-102 in PD-1 CPI refractory melanoma. For this phase 2 study, Agenus will provide their class-leading Fc-enhanced CTLA-4 (botensilimab) and PD-1 (balstilimab) CPIs for combination with ONCOS-102. Initially, the safety and efficacy of (1) a higher dose of ONCOS-102 will be tested as a monotherapy and (2) in combination with the PD-1 CPI balstilimab.
Following confirmation of the safety and efficacy of the higher ONCOS-102 dose, the study will proceed into its next phase where 2 further study cohorts are planned to be added, ONCOS-102 is combined with a CTLA-4 CPI (botensilimab) in addition to testing a triple combination of ONCOS-102, balstilimab and botensilimab.
The US Food and Drug Administration (FDA) has accepted the protocol and given the formal go ahead to proceed with the trial.
Malignant Pleural Mesothelioma
Malignant pleural mesothelioma (MPM) is a very aggressive form of lung cancer with an expected survival of less than one year from diagnosis. In a randomized phase 1/2 trial (n=31), in which ONCOS-102 was added to standard of care (SoC) chemotherapy (pemetrexed/cisplatin), a survival benefit was observed for ONCOS-102 in mesothelioma vs. SoC chemotherapy treatment alone.
Specifically, at the 30-month follow-up, 34% of ONCOS-102-treated patients (n=20) were still alive vs only 18% in the control group (n=11). Median overall survival (mOS) was 25.0 months for first-line ONCOS-102-treated patients (n=8) vs 13.5 months in the first-line SoC-only control group (n=6). The first line mOS of 25.0 months also compares favorably to historical control of 12-16 months for patients receiving the same SoC chemotherapy treatment, as well as the combination of nivolumab / ipilimumab double CPI which was recently approved as a first-line treatment option for MPM based on a phase 3 trial showing 18.1 months mOS.
Immune activation was assessed in tumor biopsies pre- and post-ONCOS-102 treatment and showed broad and powerful ONCOS-102-induced remodeling of the tumor microenvironment. In particular, this remodeling was hallmarked by increased T-cell infiltration and a shift towards pro-inflammatory immune cells, and the level of immune activation was associated with both tumor responses and survival outcomes.