PETAL protocol: a phase Ib study of pembrolizumab after transarterial chemoembolization in hepatocellular carcinoma

Abstract

Transarterial chemoembolization (TACE) is the treatment of choice for intermediate-stage hepatocellular carcinoma (HCC). Recent data suggest that TACE may boost the efficacy of anti-PD-1 immunotherapy. The authors present the trial protocol for PETAL, a phase Ib study, which will assess the safety and bioactivity of pembrolizumab, an anti-PD-1 antibody, following TACE in HCC. After a run-in phase evaluating six patients to establish preliminary safety, up to 26 additional participants will be enrolled. Pembrolizumab will be administered three-times weekly for 1 year or until progression, starting 30–45 days after TACE. The primary objective is to determine safety and the secondary objective is to preliminarily evaluate efficacy. Radiological responses will be evaluated every four cycles.

Clinical Trial Registration: NCT03397654 (ClinicalTrials.gov)

Keywords::

• hepatocellular carcinoma
• immune checkpoint inhibitor
• immunotherapy
• PD-1
• pembrolizumab
• transarterial chemoembolization

Author contributions

R Sharma and DJ Pinato were responsible for the study concept and design. P Fessas, B Scheiner and DJ Pinato drafted the manuscript. All authors were involved in the critical revision of the manuscript for important intellectual content. DJ Pinato obtained funding and supervised the study.

Financial & competing interests disclosure

The study was funded by Merck Sharpe and Dohme (MSD). The authors would like to acknowledge infrastructure support provided by the Imperial College Experimental Cancer Medicine Centre (ECMC), the Cancer Research UK Imperial Centre, the NIHR Imperial College Biomedical Research Centre and the NIHR Clinical Research Facility. A D’Alessio is supported by the NIHR Imperial BRC, by grant funding from the European Association for the Study of the Liver (Andrew Burroughs Fellowship) and Cancer Research UK (RCCPDB-Nov21/100008). B Scheiner is supported by a scientific grant from the Università degli Studi del Piemonte Orientale, Novara, Italy. A Cortellini is supported by the NIHR Imperial BRC. DJ Pinato is supported by grant funding from the Wellcome Trust Strategic Fund (PS3416) and the Associazione Italiana per la Ricerca sul Cancro (AIRC MFAG 25697). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The study was funded by Merck Sharpe and Dohme (MSD). The authors would like to acknowledge infrastructure support provided by the Imperial College Experimental Cancer Medicine Centre (ECMC), the Cancer Research UK Imperial Centre, the NIHR Imperial College Biomedical Research Centre and the NIHR Clinical Research Facility. A D’Alessio is supported by the NIHR Imperial BRC, by grant funding from the European Association for the Study of the Liver (Andrew Burroughs Fellowship) and Cancer Research UK (RCCPDB-Nov21/100008). B Scheiner is supported by a scientific grant from the Università degli Studi del Piemonte Orientale, Novara, Italy. A Cortellini is supported by the NIHR Imperial BRC. DJ Pinato is supported by grant funding from the Wellcome Trust Strategic Fund (PS3416) and the Associazione Italiana per la Ricerca sul Cancro (AIRC MFAG 25697). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.