Hepatocellular Carcinoma · Medical · Advanced / Metastatic · Post-sorafenib nivolumab/ipilimumab dose-regimen study

CheckMate 040 (Cohort 4)

Clinical question: In post-sorafenib nivolumab/ipilimumab dose-regimen study, what is the efficacy and safety of the evaluated intervention?

Registry: NCT01658878 · One underlying study; aliases and follow-up publications consolidated.

Open-label phase I/II trial; randomized cohort 4 with 148 patients allocated among three nivolumab/ipilimumab schedules. Evidence cut-off: 13 November 2026.

Design, population and eligibility

Design / sample size

Open-label phase I/II trial; randomized cohort 4 with 148 patients allocated among three nivolumab/ipilimumab schedules.

Eligibility

Advanced HCC, Child-Pugh A, previously treated with sorafenib.

Intervention

Three nivolumab/ipilimumab dosing schedules; no standard-of-care control arm.

Arm A: nivolumab 1 mg/kg + ipilimumab 3 mg/kg q3w ×4 then nivolumab maintenance; other arms used lower ipilimumab intensity/different schedules.

Comparator

As described in the study design; see primary publication.

Primary endpoint: Safety/tolerability and ORR; OS exploratory.

Key efficacy outcomes

ORR 32%, 27% and 29% across arms; median OS 22.8, 12.5 and 12.7 months, respectively. These are descriptive between-schedule outcomes, not a powered comparative efficacy result.

Source-reported outcome: ORR 32%, 27% and 29% across arms; median OS 22.8, 12.5 and 12.7 months, respectively. These are descriptive between-schedule outcomes, not a powered comparative efficacy result.

Safety and treatment delivery

Grade ≥3 TRAEs 76%, 65% and 69%; one grade 5 pneumonitis reported.

Clinical interpretation and limitations

This is randomized phase I/II dose-schedule evidence, not a phase III comparison against standard therapy. Do not interpret arm A's median OS as proof of regimen superiority.

Interpret the reported hazard ratios in the context of the prespecified endpoint, statistical hierarchy, follow-up maturity, crossover/subsequent therapy and enrolled population. Median survival differences are not risk differences and must not be converted into NNT.

Absolute effect

No NNT/NNH is displayed unless an absolute event-risk difference at a clearly stated fixed timepoint can be calculated from reported trial data. Median survival differences and hazard ratios alone do not support an NNT. The visual above uses reported outcome data only.

Primary publication and follow-up

Primary publication

Registry / follow-up / authoritative source

Source-level verification status: primary publication identified and key quoted outcomes transcribed; where full-text toxicity or procedural details were not available, the page explicitly flags the limitation rather than inferring values.

Current-practice context · 13 November 2026

This page separates historical trial results from contemporary practice. Verify the applicable jurisdictional guideline, regulatory approval, biomarker assay, liver function, comorbidity and treatment availability before applying the evidence. NCCN Guidelines Insights are not a substitute for the full NCCN guideline.

Guideline/regulatory reconciliation and browser-rendered QA remain scheduled for the subsequent quality-control pass.