DrAntonio D'Alessio

I am a Medical Oncologist and a clinical scientist with a special interest in liver cancer and immunotherapy.

As Clinical Research Fellow, I am involved as investigator in a number of pan-cancer early phase trials in the unit of Developmental Cancer Therapeutics at Imperial College London.
My main research focus is on the implementation of immune checkpoint inhibitors (ICI) in early- and intermediate-stage hepatocellular carcinoma (HCC). I am conducting a translational PhD research project aimed to identify biomarkers of response to neoadjuvant immunotherapy in HCC, with the use of a several cutting-edge technologies including spatial transcriptomics, high-throughput sequencing of gut microbiota, and analysis of circulating tumour DNA. I have been the first European researcher to present prospective data on the use of ICI prior to liver surgery in HCC. I was awarded the prestigious ASCO Merit Awards for three consecutive years (2022, 2023, 2024) and the ILCA Young Investigator Award for my translational work in the field of neoadjuvant immunotherapy for liver cancer.
I have attracted independent funding for my research, including the Cancer Research UK Predoctoral Bursary and the "Andrew K. Burroughs" Fellowship from the European Association for the Study of the Liver (EASL).
I am an active member of the main hepatology and oncology scientific societies (ESMO, ASCO, AACR, EASL, ILCA, BACR). My scientific activity has resulted in several presentations at major oncology meetings, including ASCO, EASL, ILCA, and in a number of peer-reviewed publications on high-impact journals.


Selected Publications

1. Pathological response following neoadjuvant immune checkpoint inhibitors in patients with hepatocellular carcinoma: a cross-trial, patient-level analysis. D'Alessio, Antonio et al. The Lancet Oncology, Volume 25, Issue 11, 1465 - 1475

I coordinated an international consortium of academic centres and I provided the first global benchmark for the characterisation of pathological response to neoadjuvant ICI therapy in patients with hepatocellular carcinoma. In the largest pooled prospective analysis to date, I showed at a patient level that pathological response to neoadjuvant ICI in hepatocellular carcinoma is a robust predictor of improved relapse-free survival, underscoring its potential as a clinical endpoint for future, randomised, phase 3 trials.

2. Safety and preliminary efficacy of pembrolizumab following trans-arterial chemoembolization for hepatocellular carcinoma: the PETAL phase Ib study. Antonio D’Alessio*, David J. Pinato*, Claudia Angela Maria Fulgenzi*, Alexandra Emilia Schlaak*, Ciro Celsa, Saskia Killmer, Jesus Miguens Blanco, Caroline Ward, Charalampos-Vlasios Stikas, Mark R. Openshaw, Nicole Acuti, Georgios Nteliopoulos, Cristina Balcells, Hector C. Keun, Robert D. Goldin, Paul J. Ross, Alessio Cortellini, Robert Thomas, Anna-Mary Young, Nathan Danckert, Paul Tait, Julian R. Marchesi, Bertram Bengsch, Rohini Sharma. Clin Cancer Res 2024;30:1–11.

This paper presents the results from the Imperial-led phase 1b PETAL study investigating the combination of immune checkpoint inhibitor pembrolizumab with transarterial chemoembolisation (TACE). The clinical findings are complemented by a comprehensive program of translational analyses, showing the predictive role for response to immunotherapy of ctDNA, peripheral immunophenotype of PBMCs, tumour infiltrating lymphocytes, gut microbiota, and peripheral TCR repertoire.

3. Integrated phenotyping of the anti-cancer immune response in HIV-associated hepatocellular carcinoma. Antonio D’Alessio*, David J. Pinato*, Takahiro Kaneko*, Alejandro Forner, Petros Fessas, Beatriz Minguez, Edoardo G. Giannini, Federica Grillo, Alba Díaz, Francesco A. Mauri, Claudia A.M. Fulgenzi, Alessia Dalla Pria, Robert D. Goldin, Giulia Pieri, Pierluigi Toniutto, Claudio Avellini, Maria Corina Plaz Torres, Ayse U. Akarca, Teresa Marafioti, Sherrie Bhoori, Jose María Miró, Mark Bower, Norbert Bräu, Vincenzo Mazzaferro. JHEP Reports Volume 5, Issue 7, July 2023, 100741.

We showed that HIV resected HCC were enriched with features of immune exhaustion compared to HIV- HCC, including higher expression of PD-L1, intratumoural enrichment of regulatory T cells and immune-exhausted CD8 PD-1 T cell, and a downregulation of gene signatures related to innate and adaptive immune response of the tumour samples. This groundbreaking study will inform the use of immune checkpoint inhibitors in the population of people living with HIV, who have been traditionally excluded from clinical trials.

4. Preliminary evidence of safety and tolerability of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma and Child-Pugh A and B cirrhosis: A real-world study. Antonio D’Alessio, Claudia Angela Maria Fulgenzi, Naoshi Nishida, Martin Schönlein, Johann von Felden, Kornelius Schulze, Henning Wege, Vincent E. Gaillard, Anwaar Saeed, Brooke Wietharn, Hannah Hildebrand, Linda Wu, Celina Ang, Thomas U. Marron, Arndt Weinmann, Peter R. Galle, Dominik Bettinger, Bertram Bengsch, Arndt Vogel, Lorenz Balcar, Bernhard Scheiner, Pei-Chang Lee, Yi-Hsiang Huang, Suneetha Amara, Mahvish Muzaffar, Abdul Rafeh Naqash, Antonella Cammarota, Nicola Personeni, Tiziana Pressiani, Rohini Sharma, Matthias Pinter, Alessio Cortellini, Masatoshi Kudo, Lorenza Rimassa, David J. Pinato. Hepatology. 2022;00:1–13.

This is the first study showing the safety and efficacy of the immune checkpoint inhibitor combination of atezolizumab plus bevacizumab in a population with impaired liver function (Child Pugh B). Atezolizumab plus bevacizumab is the current standard of care treatment for patients with advanced hepatocellular carcinoma (HCC). However, patients with Child Pugh B liver function are routinely excluded from clinical trials testing systemic therapy for HCC. For the first time, we showed that Child Pugh B patients who were treated in real life with the combination did not report any added safety risks, and they achieved comparable efficacy outcomes to patients with preserved liver function, thus suggesting their potential inclusion in future prospective clinical trials.

5. NASH limits anti-tumor surveillance in immunotherapy-treated HCC. Pfister, D. et al. Nature. 2021;592:450-456.

This pioneering work demonstrated that hepatocellular carcinoma (HCC) arising on a background of non-alcoholic steatohepatitis (NASH) may have suboptimal response to immune checkpoint blockade. By complementing findings from murine models with an international clinical validation dataset, this study informed the trial design for systemic therapy in HCC, which now routinely incorporates a stratification based on HCC aetiology.


Awarded Conference Abstracts

EASL - International Liver Congress 2022. Oral Presentation. PRIME-HCC: Phase Ib study of neoadjuvant ipilimumab and Nivolumab prior to liver resection for hepatocellular carcinoma.
ASCO 2022. MERIT AWARD. Preliminary results from a phase Ib study of neoadjuvant ipilimumab plus nivolumab prior to liver resection for hepatocellular carcinoma: The PRIME-HCC trial. Abstract #371770.
ASCO 2023. MERIT AWARD. Neoadjuvant immunotherapy with ipilimumab plus nivolumab leads to radiologically and pathologically quantifiable responses through modulation of the tumour microenvironment in resectable hepatocellular carcinoma. Abstract #420260.
ILCA 2023. Junior Investigator Award - Best Oral Presentation (Clinical). Predictors of response to neoadjuvant immunotherapy in resectable hepatocellular carcinoma: preliminary clinical and translational analyses from the PRIME-HCC study.
ASCO GI 2024. MERIT AWARD. Qualification of major pathological response as a surrogate endpoint for relapse-free survival following neoadjuvant immunotherapy for hepatocellular carcinoma. Abstract #506
ILCA 2024. Junior Investigator Award - Best Oral Presentation (Clinical). Pathological response following neoadjuvant immunotherapy predicts for relapse-free survival in hepatocellular carcinoma.