On January 21, 2020 Targovax ASA (OSE: TRVX), a clinical stage immuno-oncology company developing oncolytic viruses to target hard-to-treat solid tumors, reported the first set of clinical results from the randomized phase I/II trial of ONCOS-102 in combination with standard of care chemotherapy in malignant pleural mesothelioma (MPM) (Press release, Targovax, JAN 21, 2020, View Source [SID1234553385]).

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The trial is an open label, exploratory phase I/II adding ONCOS-102 to standard of care (SoC) chemotherapy (pemetrexed/cisplatin) in first and second (or later) line MPM to assess safety, immune activation and clinical efficacy of the combination treatment. In total, 31 patients have been enrolled in the randomized trial design, with 20 patients in the experimental group receiving the ONCOS-102 and SoC combination, and 11 patients in a control group receiving SoC only. All patients have completed the treatment phase (4 months for the control group and 5 months for the experimental group) and the first data have been analyzed. The combination treatment with ONCOS-102 and SoC was well tolerated, with no safety signals beyond what is expected from SoC alone.

Early data show median Progression Free Survival (mPFS) of 8.4 months (95% CI 2.0, NA) in the experimental group vs 6.8 months (95% CI 2.6, NA) in the control group. In first line patients, the mPFS was 8.9 months (n=11; 95% CI 2.1, NA) vs 6.8 months (n=6; 95% CI 2.6, NA), respectively. This compares favorably to historical control, which have reported mPFS of 5.7-7.3 months (Vogelzang 2003, Ceresoli 2006, Zalcman 2016). Although the mPFS is encouraging, many patients are still censored. Therefore, the results should be considered as emerging and will change over time. The patients continue to be followed, and updated PFS figures will be reported later in 1H20.

Overall Response Rate (ORR) and Best Overall Response Rate (BORR) in first line patients have been in the range of 20-40% in previously published studies (Vogelzang 2003, Hazarika 2005, Ceresoli 2006, Zalcman 2016), but proven a poor predictor of survival outcomes. The first line ORR and Disease Control Rate (DCR) in this trial were 30% and 90% in the experimental group (n=10, measured at 5 months), and 33% and 83% in the control group (n=6, measured at 4 months). For second (or later) line patients, ORR / DCR were 11% / 67% in the experimental group (n=9) and 60% / 80% in the control group (n=5). The unexpected control group ORR of 60% is far above previous results and experience in clinical practice. Due to the relatively small sample size none of the above data reach statistical significance.

The first set of immunological analyses show robust immune activation following ONCOS-102 treatment. In tumor biopsy immunohistochemistry (mIHC), 10 of 15 evaluable patients in the experimental group had increased tumor infiltrating CD8+ T-cells. Importantly, 9 of these 15 had increased PD-L1 expression in the tumor, of whom 7 remained progression free at the time of analysis. These results indicate a positive association between immune activation and clinical outcome, and suggests that the patients would be susceptible to combination treatment with a checkpoint inhibitor. Additional biomarker analyses are being performed and will be reported later in 1H20.

Prof. Luis Paz-Ares, Chair of the Medical Oncology Department at the Hospital Doce de Octubre, Madrid and Principal Investigator of the trial, said: "Mesothelioma remains a challenging disease with generally poor prognosis, and there is a large unmet medical need for new, innovative treatments such as ONCOS-102. We generally consider antitumor response difficult to measure in mesothelioma, and PFS may be the preferred early indicator of clinical efficacy. Although the data are preliminary and still maturing, it is encouraging to see signals of numerically improved median PFS in the ONCOS-102-treated group. The ORR in first line patients is as expected relative to historical control, whereas the DCR is higher than we normally see. We are continuing to follow the patients and it will be very interesting to track how the data matures over time."

Dr. Magnus Jäderberg, Chief Medical Officer of Targovax, said: "Completing the treatment phase of our mesothelioma trial is an important milestone for Targovax. We are pleased to see a beneficial safety and tolerability profile of the combination treatment. The high DCR and early, emerging PFS are promising, particularly in first line patients. The plan is now to continue development in the first line setting, with the addition of a checkpoint inhibitor to the ONCOS-102 and chemotherapy combination treatment, as supported by the immune activation data in our current trial. We are already in discussion with a prospective pharma partner for a future study collaboration."