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750P - A phase Ib study of pembrolizumab following trans-arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): PETAL

Title: 750P - A phase Ib study of pembrolizumab following trans-arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): PETAL
Authors: Pinato, DJ
Cole, T
Bengsch, B
Tait, P
Sayed, AA
Abomeli, F
Gramenitskaya, D
Allara, E
Thomas, R
Ward, C
Wong, CN
Akarca, AU
Blanco, JM
Marafioti, T
Marchesi, J
Sharma, R
Item Type: Conference Paper
Abstract: Background The efficacy of TACE is secondary to its dual ischaemic and cytotoxic effect, which promotes immunogenic tumor cell death. TACE may prime adaptive immunity and facilitate pembrolizumab (pembro; anti-PD1) in promoting tumour immune rejection and improve outcome in HCC. We designed this phase Ib study to evaluate safety, preliminary activity of TACE+pembrolizumab and explore mechanisms of efficacy. Methods Up to 32 patients (pts) with intermediate-stage HCC were planned to receive up to 2 rounds of conventional TACE followed by pembro 200 mg q3w 30 days post-TACE until disease progression or unacceptable toxicity for up to 1 year. Primary endpoint was safety with dose-limiting toxicities emerging from the combination being evaluated over a 21-days window from commencement of pembro. Secondary endpoints included PFS rates q12w. We explored tumour and host determinants of response in tissue, blood and stool samples to confirm the bioactivity of the combination. Results In cohort 1 (n = 6) patients were all of BCLC-B stage, 83% males, 16% HCV-positive, 50% ECOG PS 0, median age 62 years. Child-Pugh (CP) was A in 5 and B7 in 1 pt. Median tumour size was 4 cm, and median number of lesions was 2. All-grade adverse events potentially related to treatment (tx) occurred in 50% of pts including diarrhoea (n = 1, G3), skin rash (n = 2, G2), infusion reaction (n = 1, G2) and adrenal insufficiency (n = 1, G2). Pembro yielded no synergistic toxicity with TACE and no DLTs were reported. At data cut-off, tx was ongoing for 3 pts with a median duration of tx of 2.8 months. Of the 4 radiologically evaluable patients, 3 had stable disease on pembro, 1 had progressive disease. Cause of withdrawal included disease progression/death (n = 2) and worsening liver failure in the CP B7 pt, non tx-related (n = 1). Updated data from an expanded pt cohort will be shown and efficacy data will be correlated with T-cell responses to recognized tumor-associated antigens, tumour-infiltrating lymphocyte profiling and stool bacterial metagenomics. Conclusions The TACE+pembro combination had a tolerable safety profile with no evidence of synergistic toxicity. Alongside emerging efficacy data, this encourages the clinical development of the combination in CP A pts. Clinical trial identification NCT03397654.
Issue Date: 8-Jan-2020
Date of Acceptance: 1-Jan-2020
URI: http://hdl.handle.net/10044/1/87637
DOI: 10.1093/annonc/mdz247.076
ISSN: 0270-9139
Publisher: Wiley
Start Page: 209A
End Page: 210A
Journal / Book Title: Hepatology
Volume: 70
Copyright Statement: © 2019 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.
Sponsor/Funder: Merck Sharp & Dohme (UK) Ltd.
Funder's Grant Number: 8102174357
Conference Name: Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Liver Meeting
Keywords: Science & Technology
Life Sciences & Biomedicine
Gastroenterology & Hepatology
Science & Technology
Life Sciences & Biomedicine
Gastroenterology & Hepatology
Gastroenterology & Hepatology
1101 Medical Biochemistry and Metabolomics
1103 Clinical Sciences
1107 Immunology
Publication Status: Published
Start Date: 2019-11-08
Finish Date: 2019-11-12
Conference Place: Boston, MA
Open Access location: https://www.annalsofoncology.org/article/S0923-7534(19)58966-9/abstract
Online Publication Date: 2020-01-08
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Department of Surgery and Cancer
Department of Infectious Diseases
National Heart and Lung Institute