Lead compound ONCOS-102 has shown class-leading clinical data in both monotherapy and in combinations with checkpoint inhibitor and chemo.
Combination with checkpoint inhibitor
Impressive objective responses as well as effects on non-injected lesions in ONCOS-102 trial in anti-PD1 refractory melanoma patients. In this two-part, open label phase 1 trial the combination of ONCOS-102 and the anti-PD1 checkpoint inhibitor (CPI) pembrolizumab has been tested in patients with advanced, unresectable melanoma who have had disease progression despite treatment with anti-PD1 CPI. This is a particularly challenging patient population, which is resistant to approved immunotherapies and has few treatment alternatives available.
For the trial overall, tumor responses were observed in 7 out of 20 evaluable patients treated with the ONCOS-102 and pembrolizumab combination, translating into an ORR of 35% by RECIST 1.1 criteria. In addition, there were multiple examples of responses in non-injected lesions, including 2 patients where a non-injected lesion completely disappeared, indicating that ONCOS-102 can induce systemic anti-tumor immunity.
Combination with chemotherapy
Encouraging survival data for ONCOS-102 in mesothelioma. In this phase 1/2 trial ONCOS-102 has been tested in combination with standard-of-care (SoC) chemotherapy in patients with malignant pleural mesothelioma (MPM). An 18-month analysis showed that median Overall Survival (mOS) will be at least 18.2 months for first-line patients receiving ONCOS-102 plus chemotherapy, compared to mOS of 14.2 months or less in the chemotherapy-only control group.
The ONCOS-102 treatment induces broad and powerful immune activation in MPM, far beyond what is achieved with SoC alone. Importantly, this immune activation is associated with better survival outcomes at the 18-month analysis, indicating that the immunological activity of ONCOS-102 drives the observed clinical benefit. The powerful immune activation generated by ONCOS-102 builds a strong rationale for combining ONCOS-102 with a checkpoint inhibitor in MPM. This combination could provide further clinical benefits in this indication.
Monotherapy
ONCOS-102 showed encouraging phase 1 efficacy data in a challenging patient population. In a phase 1 monotherapy trial in 12 end-stage patients with various solid tumors, all patients showed hallmarks of immune activation following ONCOS-102 treatment and 11 out of 12 patients had an increase in CD8+ T-cell tumor infiltration compared to baseline. The immune activation could be correlated to overall survival on several parameters, with 40% of patients showing stable disease at the end of the trial, and this persisted for three years in one ovarian cancer patient. This is a remarkable finding considering the generally immune-suppressed status of late stage cancer patients who have exhausted all other treatment options and have short life expectancy.