Mesothelioma Tumors Respond to ONCOS-102 Plus Pemetrexed and Cisplatin

Patients with malignant pleural mesothelioma in a phase I/II trial (NCT02879669) who received ONCOS-102 added to standard of care (SoC) pemetrexed- and cisplatin-based chemotherapy in the first-, second-, and later-line settings showed a progression-free survival (PFS) after 9 months of follow-up that was consistent with previously published data, announced Targovax ASA. ONCOS-102 also led to immune activation in patients, providing further validation of the drug’s clinical activity for use in multiple settings of mesothelioma.¹

“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,” said Luis G. Paz-Ares, MD, PhD, professor, and chair of the Medical Oncology Department at the 12 de Octubre University Hospital, and principal investigator of the study, when the original findings were released.²

The trial of the immune-priming granulocyte-macrophage colony-stimulating factor–coding adenovirus is focused on first-line treatment of mesothelioma. As development of the agent continues, the focus will be frontline patients who are responding well to the drug. The 12-month clinical findings along with extensive immune activation and biomarker data will be reported in mid-2020.

Early data from the study were released in January and demonstrated clinical efficacy in 31 frontline patients as well as immune activation. The participants were randomized to receive either ONCOS-102 plus SoC (n = 20) or SoC alone (n = 11). Patients in the combination arm had completed 4 months of treatment and those in the control arm had received 5 months of treatment before the first data were analyzed.²

The experimental combination led to a PFS of 8.4 months (95% CI, 2.6-NA) compared with the 6.8-month PFS achieved with SoC (95% CI, 2.6-NA). The PFS results were found to be comparable with historical control data showing a PFS of 5.7 months to 7.3 months in this patient population. At the time these survival findings were reported, findings from multiple patients were still censored and the results were therefore considered emerging.

The first-line overall response rate (ORR) observed at 5 months was 30% in the combination arm and 30% in the control arm, at 4 months. The disease control rate in the 2 arms were 90% and 83%, respectively. The second-line ORR in the combination group was 11% with a DCR of 67%. In the control group, the ORR was 60% with an 80% DCR in second-line patients. The investigators found it notable that the ORR seen in the control group was higher than historical data. The data in this study were not statistically significant due to the small sample size though.

“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,” Paz-Ares added.

In terms of immune activation, 10 out of 15 evaluable patients in the combination arm showed increased tumor-infiltrating CD8+ T-cells on their tumor biopsy immunohistochemistry. Remarkably, increased PD-L1 expression in the tumor was observed in 9 patients and 7 of those patients remained progression free at the time the efficacy data were analyzed.

ONCOS-102 also demonstrated a positive safety profile in this study.

The study consists of a phase I safety lead-in cohort of 6 patients who received the experimental combination followed by a randomized phase. Patients with unresectable, advanced, malignant pleural mesothelioma were enrolled regardless of line of treatment.

The primary end point of the ongoing, open-label, randomized study was the number of participants with adverse events. PFS, immune activation, ORR, overall survival, the presence of tumor antigen CD8+ cells, and clinical outcome by time to PFS and OS event end points were explored as secondary end points in the study.

_References:

_{1. Targovax releases update for mesothelioma trial combining ONCOS-102 and chemotherapy [news release]. Oslo, Norway: Targovax ASA; May 4, 2020. https://bit.ly/2WsFwmM. Accessed May 5, 2020.}

_{2. Targovax announces encouraging data in mesothelioma study combining ONCOS-102 and standard of care chemotherapy [news release]. Oslo, Norway: Targovax ASA; January 21, 2020. https://bit.ly/3c9nahk. Accessed May 5, 2020.}