A phase ib study of pembrolizumab following trans-arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): Petal

Background: The efficacy of TACE is secondary to its dual ischaemic and cytotoxic effect, which promotes immunogenic tumor cell death. We hypothesized TACE to 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 the TACE+pembrolizumab combination 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 study cohort 1 (n=6) patients were all of BCLC-B stage, 83% males, 16% HCV-positive, 50% ECOG PS 0 with a median age of 62 years Child-Pugh (CP) class was A in 5 pts and B7 in 1 pt Median tumour size was 4 cm, and median number of tumour nodules was 2 All-grade adverse events potentially related to treatment (tx) all-grade occurred in 50% of patients 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, baseline tumour-infiltrating lymphocyte profiling and stool bacterial metagenomics Conclusion: 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 CPA pts.