750P - A phase Ib study of pembrolizumab following trans-arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): PETAL
Author(s)
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.
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.
Date Issued
2020-01-08
Date Acceptance
2020-01-01
Citation
Hepatology, 2020, 70, pp.209A-210A
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
Merck Sharp & Dohme (UK) Ltd.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000488653500326&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
8102174357
Source
Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) / Liver Meeting
Subjects
Science & Technology
Life Sciences & Biomedicine
Gastroenterology & Hepatology
Publication Status
Published
Start Date
2019-11-08
Finish Date
2019-11-12
Coverage Spatial
Boston, MA
Date Publish Online
2020-01-08