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.

Gastrointestinal (Noncolorectal) Cancer
Session Type and Session Title: 
Poster Discussion Session, Gastrointestinal (Noncolorectal) Cancer
Abstract Number: 


Poster Board Number: 
Board #4
J Clin Oncol 34, 2016 (suppl; abstr 4012)
Anthony B. El-Khoueiry, Bruno Sangro, Thomas Cheung Yau, Todd S. Crocenzi, Theodore Hobart Welling, Winnie Yeo, Akhil Chopra, Jeffrey Anderson, Christine Marie Dela Cruz, Lixin Lang, Jaclyn Neely, Ignacio Melero; University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA; Clinica Universidad de Navarra and CIBERehd, Pamplona, Spain; University of Hong Kong, Hong Kong, China; Providence Cancer Center, Portland, OR; University of Michigan, Ann Arbor, MI; Johns Hopkins Singapore International Medical Centre, Singapore, Singapore; Bristol-Myers Squibb, Princeton, NJ

Abstract Disclosures


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


ORR7 (15)
    CR, n (%)3 (6)
    PR, n (%)4 (8)
    SD, n (%)24 (50)
    PD, n (%)15 (31)
    Not evaluable2 (4)
Median DOR, mo23.7
Pts with decline in tumor burden from baseline, n (%)17 (37)
Median OS,a (95% CI), mo15.1 (9.6, 28.6)
OS Rate,a %
    6 mo67
    9 mo67
    12 mo59
    18 mo48

aBased on entire pt population.