The IMMULAB trial: A phase II trial of immunotherapy with pembrolizumab in combination with local ablation for patients with early stage hepatocellular carcinoma (HCC).

Abstract

TPS4159 Background: The investigator-initiated IMMULAB study investigates the clinical activity of peri-interventional treatment with the anti-PD1 antibody pembrolizumab in HCC patients who are candidates for local ablation via either radiofrequency ablation (RFA), microwave ablation (MWA) or brachytherapy, or - as recommended for tumor larger than 3 cm – by combination with TACE. Patients with extrahepatic disease are excluded. Local ablation is known to induce tumor destruction with subsequent antigen release resulting in host adaptive immune responses. However, tumors could quickly overcome the immune responses by upregulating PD-L1/PD-1 expression and inhibiting the function of CD8+ and CD4+ T cells. Thus, combination of local ablation with an anti-PD1 antibody might display interesting effects by activating immune cells and disabling immune inhibitory mechanisms at the same time. Methods: This is a prospective investigator initiated single-arm multicenter phase II trial investigating immunotherapy with the PD-1 inhibitor pembrolizumab in combination with local ablation in early stage hepatocellular carcinoma (HCC). Patients with a child-pugh classification score ≤ 6, including high risk candidates for local ablation (defined as patients having ≤ 5 tumor nodules with diameters ≤ 7cm [longest axis] each OR patients with vascular infiltration) receive 200mg pembrolizumab i.v. q3w for 2 cycles. Thereafter, radiologic imaging is followed by local ablation on day 1 of cycle 3. Further pembrolizumab (200mg) is applied 2 days after ablation and thereafter every 3 weeks (q3w) for a total treatment duration of up to 12 months. It is planned to enroll 30 pts. Primary efficacy endpoint is the overall response rate (RECIST 1.1) after 2 cycles of pembrolizumab and before performing local ablation aiming in the conversion / downstaging of borderline candidates by pre-interventional treatment with pembrolizumab. Overall recruitment has started; currently (Feb 2021) 18 of 30 planned patients have been enrolled. Clinical trial information: NCT03753659.