Mesothelioma

ONCOS-102 in malignant pleural mesothelioma


Malignant pleural mesothelioma (MPM) is a rare cancer of the lining of the lung, which is believed to be mainly caused by exposure to asbestos or industrial pollution. It is a very aggressive form of cancer, and the expected survival for MPM patients is less than one year from diagnosis. Currently, there are no curative treatment options available for MPM, however, standard treatments such as surgery, chemotherapy and radiotherapy can help improve prognosis and prolong life expectancy. Treatment with the chemotherapy combination of pemetrexed and cisplatin (Pem-Cis) is the only widely recognized standard of care (SoC) for UNRESECTABLE MPM, but the median progression-free survival (PFS) is only 6 months and median overall survival (mOS) 12 months from the initiation of treatment. Therefore, there is a high unmet medical need for patients suffering from this difficult-to-treat cancer.

Two end-stage MPM patients were included in Targovax’s Phase I basket trial testing ONCOS-102 as a single agent, with PROMISING results. Both of these patients showed immune activation, both systemically and at the lesional level, indicating that ONCOS-102 can turn “cold” MPM tumors “hot” (Ranki et al. 2016). Strikingly, one of the patients had a 47% reduction in tumor volume 6 WEEKS AFTER completing the trial and went on to live for 18 months, far longer than expected. As a next step, the effect of combining ONCOS-102 and Pem-Cis was assessed in an MPM mouse model, demonstrating synergistic anti-tumor activity of the combination (Kuryk et al. 2016). Following up on this work, it was shown that ONCOS-102 induces the activation of mesothelin-specific T-cells in mice with mesothelin-positive tumors, indicating that ONCOS-102 is capable of driving an MPM tumor-specific immune response.

Based on these findings Targovax has initiated a randomized, 30-patient phase I/II clinical trial combining ONCOS-102 with Pem-Cis in patients with non-operable MPM (ClinicalTrials.gov Identifier: NCT02879669). To date, early data from the 6-patient safety cohort has been released, showing that the combination of ONCOS-102 with Pem-Cis is well-tolerated, and a disease control rate of 50% after six months. Patients are now being recruited into the randomized part of the trial, and the full data set is expected during the first half of 2020.