A single centre phase II trial to assess the immunological activity of TroVax® plus pemetrexed/cisplatin in patients with malignant pleural mesothelioma – the SKOPOS trial

Abstract

Vaccines in combination with chemotherapy have been shown to be safe in different tumor types. We investigated the immunological activity of the TroVax Ò vaccine in combination with pemetrexed-cisplatin chemotherapy in malignant pleural mesothelioma (MPM).In this first line, open-label, single-arm, phase 2 study, patients with locally advanced or metastatic MPM were enrolled. Eligible patients received up to 9 intramuscular injections of TroVax Ò , starting two weeks before chemotherapy and continuing at regular intervals during and after chemotherapy to 24 weeks. The primary endpoint was the induction of cellular or humoral anti-5T4 immune response (defined as a doubling of either response at any of six follow-up time points), with a target response rate of 64%.Of 27 patients, enrolled between Feb 2013-Dec 2014, 23 (85%) received at least three doses of TroVax Ò and one cycle of chemotherapy and were included in the per-protocol analysis (PPA). 22/23 patients (95.6%) developed humoral or cellular immune response to 5T4. Thus, the study reached its primary endpoint. Disease control was observed in 87% of patients (partial response: 17.4%, stable disease: 69.6%). The median progression-free survival was 6.8 months and median overall survival 10.9 months. Treatment-related adverse events were comparable to those observed in patients with chemotherapy alone. Translational immunology studies revealed a circulating baseline immune signature that was significantly associated with long-term (>20 months in n D 8/23, 34.8%) survival.In this phase 2 trial, TroVax Ò with pemetrexed-cisplatin chemotherapy showed robust immune activity, acceptable safety and tolerability to warrant further investigation in a phase 3 setting.

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“…It achieved its clinical endpoint of generating an immune response, reporting that 22/23 (95.6%) of patients developed an immune response to TAA 5T4 post‐vaccination. 17/23 (74%) mounted humoral responses, and 20/23 (87%) patients developed ≥2x cellular immune response compared to baseline 72 …”