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
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
Vaccines in combination with chemotherapy have been shown to be safe in different tumor types. We investigated the immunological activity of the TroVax® 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®, 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® 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 = 8/23, 34.8%) survival.In this phase 2 trial, TroVax® with pemetrexed-cisplatin chemotherapy showed robust immune activity, acceptable safety and tolerability to warrant further investigation in a phase 3 setting.
1-11
Lester, Jason F.
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Casbard, Angela C.
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Al-Taei, Saly
288d5332-577c-41a4-9369-af5d9a70fe81
Harrop, Richard
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Katona, Lajos
49b50cc8-ce1e-4373-b2e0-3f2b82800b57
Attanoos, Richard L.
14551b96-ddbb-4f8d-9dc8-6d50364a648b
Tabi, Zsuzsanna
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Griffiths, Gareth O.
7fd300c0-d279-4ff6-842d-aa1f2b9b864d
7 September 2018
Lester, Jason F.
3a715211-2b06-4c31-b02b-ceeb9e757a2a
Casbard, Angela C.
b459a5a2-036d-4916-b3b7-d4a4e07221cc
Al-Taei, Saly
288d5332-577c-41a4-9369-af5d9a70fe81
Harrop, Richard
387bf614-f5be-47e6-b993-7c00747fad8a
Katona, Lajos
49b50cc8-ce1e-4373-b2e0-3f2b82800b57
Attanoos, Richard L.
14551b96-ddbb-4f8d-9dc8-6d50364a648b
Tabi, Zsuzsanna
ea45ede8-1a6c-4aa5-92d7-de5a9b176d15
Griffiths, Gareth O.
7fd300c0-d279-4ff6-842d-aa1f2b9b864d
Lester, Jason F., Casbard, Angela C., Al-Taei, Saly, Harrop, Richard, Katona, Lajos, Attanoos, Richard L., Tabi, Zsuzsanna and Griffiths, Gareth O.
(2018)
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.
OncoImmunology, 7 (12), , [e1457597].
(doi:10.1080/2162402X.2018.1457597).
Abstract
Vaccines in combination with chemotherapy have been shown to be safe in different tumor types. We investigated the immunological activity of the TroVax® 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®, 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® 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 = 8/23, 34.8%) survival.In this phase 2 trial, TroVax® with pemetrexed-cisplatin chemotherapy showed robust immune activity, acceptable safety and tolerability to warrant further investigation in a phase 3 setting.
Text
10.1080_2162402X.2018.1457597
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10.1080@2162402X.2018.1457597
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Accepted/In Press date: 20 March 2018
e-pub ahead of print date: 9 April 2018
Published date: 7 September 2018
Identifiers
Local EPrints ID: 423164
URI: http://eprints.soton.ac.uk/id/eprint/423164
ISSN: 2162-402X
PURE UUID: 549e0f7e-037f-49c4-a069-612e8eaba0b1
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Date deposited: 19 Sep 2018 16:30
Last modified: 16 Mar 2024 07:05
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Contributors
Author:
Jason F. Lester
Author:
Angela C. Casbard
Author:
Saly Al-Taei
Author:
Richard Harrop
Author:
Lajos Katona
Author:
Richard L. Attanoos
Author:
Zsuzsanna Tabi
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