Phase Ib/Ii Study Of Sorafenib (Sor) And Pembrolizumab (Pem) In Advanced Hepatocellular Cancer (Hcc)

TPS596 Background: SOR has been the backbone of advanced HCC therapy with poor outcome. Anti-PD-1 therapy is approved as a second-line treatment option in HCC due to its promising efficacy and safety. Our preclinical work showed that SOR is immunomodulatory and may be synergistic when combined with anti-PD-1 therapy. Guided by this data, we initiated this multicenter study of SOR and PEM in advanced HCC patients (pts). Methods: Pts who have Child-Pugh Class A, ECOG PS of 0/1, biopsy-proven measurable HCC that is unresectable or metastatic, are included. Pts must not receive either SOR or anti-PD-1 therapy before. A total of 27 pts will be enrolled from 2 sites. Pts must have the following lab values: ANC ≥ 1,500/ mc; Hgb ≥ 8.5 g/dL; Plts ≥75,000/ mcL; serum total bilirubin ≤ 2.0 mg/dL; AST/ALT ≤ 5 X ULN; serum creatinine ≤ 1.5 X ULN. Pts with active hep B must be on antiviral therapy. Pts would be on a 4-week run-in of SOR alone at 400mg BID to ensure tolerability and stable dose (minimum 200 BID) before beginning PEM 200mg IV q3 weeks. Both drugs would be administered until progression or unacceptable toxicity with response assessment q6 weeks by RECIST 1.1 criteria. Primary endpoint: response rate. Secondary endpoints: safety, overall survival, and progression-free survival. Correlative Endpoints: Pre-treatment levels of immunosuppressive cells and the functional activity of effector T cells would be compared to post-treatment blood and tumor samples. The first 6 pts who completed 4 weeks of SOR-only treatment and began the combination therapy (addition of PEM at a fixed dose of 200 mg Q3W) would comprise the safety lead-in. Pts who withdrew before initiation of combination therapy (for reasons other than DLT) would be replaced. Dose-Limiting toxicity was defined as any ≥ grade 3 clinically significant toxicity, which is deemed possibly treatment-related and occurs within the first cycle of combination therapy. Toxicity would be assessed by NCI CTCAEV4.0. Status: First patient enrollment on 12/19/2017. On 11/28/2018, our 6th patient completed the SOR lead-in phase and began combination treatment with SOR and PEM. As of Sept 12, 2019, thirteen pts have enrolled, and 9 pts have received combination treatment. Support: Merck. Clinical trial information: NCT03211416.