Nivolumab (NIVO) + ipilimumab (IPI) + cabozantinib (CABO) combination therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC): Results from CheckMate 040.
Bibliographic record
Abstract
478 Background: The programmed death-1 inhibitor NIVO had durable responses and a manageable safety profile in pts with aHCC in CheckMate 040 (NCT01658878; El-Khoueiry et al. Lancet 2017) and is approved in the United States, Canada, Australia, and elsewhere for sorafenib (SOR)-treated pts with aHCC. In another CheckMate 040 cohort, NIVO + IPI combination therapy had durable responses in SOR-treated pts with aHCC, with objective response rates (ORRs) > 30% in each dosing arm (Yau et al. J Clin Oncol 2019). CABO is also approved for SOR-treated pts with aHCC; a pivotal phase 3 trial reported median overall survival (OS) of 10.2 mo (Abou-Alfa et al. N Engl J Med 2018). This is the first report of efficacy and safety of NIVO + CABO +/- IPI (doublet and triplet) combinations in pts with aHCC. Methods: SOR-naive or -experienced pts with aHCC were randomized to 2 arms: [1] NIVO 240 mg Q2W + CABO 40 mg daily or [2] NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W + CABO 40 mg daily. Treatment continued until intolerable toxicity or disease progression. Primary endpoints included ORR (investigator assessed using RECIST v1.1) and safety/tolerability. Data cutoff was January 2019. Results: 71 pts were randomized to NIVO + CABO (n = 36) or NIVO + IPI + CABO (n = 35). Investigator-assessed ORR was 17% (6 pts with partial response [PR]) in the NIVO + CABO arm and 26% (9 pts with PR) in the NIVO + IPI + CABO arm. Disease control rate was 81% for the NIVO + CABO arm and 83% for the NIVO + IPI + CABO arm; median progression-free survival was 5.5 mo for the NIVO + CABO arm and 6.8 mo for the NIVO + IPI + CABO arm. Median OS was not reached in either arm. Grade 3-4 treatment-related adverse events (TRAEs) were reported in 15 pts (42%) in the NIVO + CABO arm and 25 pts (71%) in the NIVO + IPI + CABO arm and led to discontinuation in 1 (3%) and 7 (20%) pts, respectively. No new safety signals were observed in either arm. Updated data describing the efficacy and safety of the combinations will be shown. Conclusions: In pts with aHCC, NIVO + CABO +/- IPI combination therapy led to clinically meaningful responses. Although the triplet had a higher rate of TRAEs observed than the doublet regimen, the majority of AEs were manageable and reversible. Clinical trial information: NCT01658878.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".