The company has completed the safety lead-in cohort and preliminary immune activation data in the phase I/II trial of ONCOS-102 in mesothelioma in combination with standard of care chemotherapy has been announced.
The trial is a randomized phase I/II open label trial, with a six-patient safety lead-in cohort, of ONCOS-102 and pemetrexed/cisplatin, the current standard of care chemotherapy, in 1st and 2nd line patients with unresectable malignant pleural mesothelioma. The trial aims to assess safety, tumor targeted immune activation and clinical benefit of the combination of ONCOS-102 and chemotherapy compared to chemotherapy alone.
The independent Data and Safety Monitoring Board (DSMB) have now reviewed all six patients in the safety lead-in cohort of the trial. No concerns were raised, and the DSMB have recommended that the randomized part of the trial can be initiated, with recruitment of another 24 patients.
Early immune activation
In addition, early immune activation has been assessed for a subset of the patients. Systemic release of several pro-inflammatory cytokines was observed (3/3 patients analyzed), demonstrating that the treatment triggers an innate immune response. Also, there was an increase in the relative level of tumor infiltrating cytotoxic CD8+ T-cells (2/2 patients with pre- and post-treatment biopsies analyzed), indicating an activation of the adaptive immune system in the lesions. These data are important, as they show that the treatment of ONCOS-102 in combination with chemotherapy induces both innate and adaptive immune activation in patients, as well as triggering changes in the tumor microenvironment, which indicate that the tumors may become susceptible to an attack by the immune system.
“We are very pleased that the safety lead-in cohort was completed without any concerns, and that we now can move into the randomized part of the trial. The systemic and lesional immune activation are in line with what we saw in the mesothelioma patients from our phase I trial, in which there was an associated clinical response. It will therefore be interesting to follow what clinical benefits may be seen in the subsequent randomized part of the ongoing trial,” said Magnus Jäderberg, CMO of Targovax.