Results from a preclinical study using a mesothelioma animal model demonstrate a synergic effect of ONCOS-102, a genetically modified adenovirus, in combination with pemetrexed and cisplatin.
“These findings give a strong rationale for the clinical testing of ONCOS-102 in combination with pemetrexed and cisplatin in patients suffering from malignant mesothelioma. In fact, we recently started a clinical trial in malignant mesothelioma where this combination will be evaluated,” said Lukasz Kuryk, of Targovax Research and Development, in a press release.
The study report, “Synergistic anti-tumor efficacy of immunogenic adenovirus ONCOS-102 (Ad5/3-D24-GM-CSF) and standard of care chemotherapy in preclinical mesothelioma model,” was published in the International Journal of Cancer.
The median overall survival for a mesothelioma cancer patient is less than one year from diagnosis. Pemetrexed-cisplatin is the standard of care chemotherapy for malignant mesothelioma, but the median progression-free survival and overall survival from the start of treatment is still 12 months.
ONCOS-102 is a dual targeting, chimeric oncolytic adenovirus, coded for human GM-CSF (granulocyte-macrophage colony-stimulating factor) — a protein secreted by some immune cells. The safety and immune activating properties of ONCOS-102 were already assessed in a phase 1 study (NCT01598129) that revealed treatment with the drug induced tumor specific immune activation both at lesional and systemic level. In addition, the immune activation came with clinical benefit.
In the new preclinical trial, researchers used a mouse model of human malignant mesothelioma, to evaluate the antitumor activity of combining pemetrexed, cisplatin, carboplatin and ONCOS-102. The results revealed that treatment with ONCOS-102 induced immunogenic cell death of human mesothelioma cells and showed anti-tumor activity in the animal model.
There was no anti-tumor activity when chemotherapy was used alone, but treatment with ONCOS-102 slowed tumor growth. There was a synergistic anti-tumor effect when chemotherapy was used in combination with ONCOS-102.
Targovax is currently conducting a Phase Ib/II trial in 30 patients with malignant mesothelioma to evaluate ONCOS-102 in combination with pemetrexed and cisplatin. The trial incorporates a phase Ib safety lead-in group of six patients. The first patient was dosed in June.
The company is set to begin ONCOS-102 combination clinical trials in several solid tumor indications: mesothelioma in combination with standard of care chemotherapy; both melanoma and ovarian cancer in combination with an immune checkpoint inhibitor; and prostate cancer in combination with a dendritic cell vaccine.
