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Hello, my name is Lorenza Rimassa. I'm the Deputy Director of the Medical Oncology Unit of Humanitas Cancer Center in Milano, Italy. And I'm going to present the results of the METIV-HCC Phase III trial of second-line Tivantinib versus placebo, in patients with MET-High hepatocellular carcinoma.
Sorafenib and regorafenib are approved systemic agents for patients with advanced hepatocellular carcinoma. Lenvatinib has shown non-inferiority results compared to sorafenib. MET, the receptor tyrosine kinase for hepatocyte-growth factor (HGF) is involved in cancer progression and metastasis. Tivantinib, a selective oral MET inhibitor, improved overall survival and progression-free survival versus placebo in a phase II study in MET-high HCC patients. Based on the results of the phase II study, 340 patients are from the Americas, Australia, Europe, and New Zealand, were enrolled in this phase III trial. Patients with MET-high second-line HCC. Patients were randomized 2:1. To Tivantinib, 226 patients, or placebo, 114 patients, and were stratified by extrahepatic spread, vascular invasion, and AFP.
The primary endpoint of the study was overall survival in the intent to treat population. Secondary endpoints were progression-free survival, assess a central radiology by RECIST 1.1 based on scans preformed every eight weeks, and safety.
Baseline patient characteristics were well balanced between the two study arms and with regard to prior sorafenib treatment, median time on sorafenib and median time from last sorafenib dose were well balanced in the two study arms. In terms of reasons for sorafenib discontinuation, slightly more patients on placebo discontinuing due to intolerance. Once, slightly more patients on tivantinib discontinuing due to radiographic progressions.
As shown in the top table, we tested the 1125 tumor samples. Half of them were MET-high overall. However, when the biopsy was taken before sorafenib, 33% of the patients were MET-high. When the biopsy was taken after sorafenib, 69% of the patients were MET-high. Also, MET expression intensity was very different between MET-high and MET-low patients with a median score of 170 in MET-high and 90 in MET-low patients.
The bottom table shows that of the 191 MET-high tumor samples, 33% came from biopsies taken before sorafenib, while 67% came from biopsies taken after sorafenib. Immunohistochemistry was performed by the central lab, and a subsequent analysis by an independent lab on a subset of samples was not conclusive due to reader and assay differences, and final results are still pending.
The study did not meet the primary end point of overall survival, with a median overall survival of 8.4 months on tivantinib, and 9.1 months on placebo, with no difference between the two treatment arms.
Also we didn't observe any difference in terms of progression-free survival with a medium progression-free survival of 2.1 months on tivantinib and 2 months on placebo. Most common adverse events were well balanced between the two study arms with no difference in particular attempts of grade 3 or higher adverse events.
In conclusion, tivantinib at 120 mg BID did not improve survival in MET-high HCC patients who have progressed on or were intolerant to sorafenib. Survival of MET-high patients on placebo was 9.1 months, longer than any prior reported survival on placebo in a phase 3 trial in HCC regardless of treatment line or biological selection. Adverse events were manageable at the final established dose of 120 mg BID. Thank you very much for your kind attention.