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Phase I/II safety and antitumor activity of nivolumab (nivo) in patients (pts) with advanced hepatocellular carcinoma (HCC): Interim analysis of the CheckMate-040 dose escalation study.
Background: For pts with advanced HCC on sorafenib (sor), overall survival (OS) is 11 mo; median OS with best supportive care (BSC) post-sor failure is 7–8 mo.Safety and preliminary antitumor efficacy of nivo, a fully human IgG4 mAb PD-1 inhibitor, was evaluated in a multiple ascending-dose, phase 1/2 study in pts with advanced HCC with clinical follow-up to 3 yrs. Methods: Pts had histologically-confirmed, advanced HCC, Child-Pugh (CP) score ≤ 7, and previously failed, refused, or were intolerant of sor. Dose escalation occurred in 3 parallel cohorts by etiology: no active hepatitis virus infection, HBV-infection, or HCV-infection. Pts received nivo 0.1–10 mg/kg for up to 2 yrs. The primary endpoint was safety. Secondary endpoints included antitumor activity by RECIST 1.1 and DOR; exploratory endpoints included biomarker assessment. Results: 51 pts were enrolled and treated with nivo: baseline CP scores were 5 (n=44) or 6 (n=7), 76% had extrahepatic metastasis, 12% had vascular invasion, and 73% had prior sor. 10 pts remain on study; 41 discontinued, most (n=35) due to PD and 1 due to a treatment-related adverse event (TRAE) of ALT and AST increase. TRAEs occurred in 39 pts (77%); most common were rash and AST increase (20% each). Grade 3-4 TRAEs were seen in 10 pts (20%); most common were AST increase (10%), lipase and ALT increase (6% each). A maximum tolerated dose was not reached. Efficacy data are reported in the Table. 48 pts were evaluable for response. Responses were observed in pts with and without quantifiable PD-L1 as assessed by IHC. Antiviral responses in HCV-infected pts have been observed. Conclusions: Nivo was well tolerated with a manageable safety profile. Treatment produced durable responses and disease stabilization across all dose levels and cohorts. Reported OS rates were favorable relative to historical data for BSC. Clinical trial information: NCT01658878
|CR, n (%)||3 (6)|
|PR, n (%)||4 (8)|
|SD, n (%)||24 (50)|
|PD, n (%)||15 (31)|
|Not evaluable||2 (4)|
|Median DOR, mo||23.7|
|Pts with decline in tumor burden from baseline, n (%)||17 (37)|
|Median OS,a (95% CI), mo||15.1 (9.6, 28.6)|
|OS Rate,a %|
aBased on entire pt population.
Abstracts by Anthony B. El-Khoueiry:
First in human (FIH) study of an OX40 agonist monoclonal antibody (mAb) PF-04518600 (PF-8600) in adult patients (pts) with select advanced solid tumors: Preliminary safety and pharmacokinetic (PK)/pharmacodynamic results.Meeting: 2016 ASCO Annual Meeting | Abstract No: 3079
Phase I study of DKN-01, an anti-DKK1 antibody, in combination with gemcitabine (G) and cisplatin (C) in patients (pts) with advanced biliary cancer.Meeting: 2016 ASCO Annual Meeting | Abstract No: e15603