Early Safety Results from the Phase 3b SIERRA Study of Durvalumab and Tremelimumab as First-Line Treatment for Participants with Unresectable Hepatocellular Carcinoma and a Poor Prognosis
Bibliographic record
Abstract
Introduction: Subgroups of people with unresectable hepatocellular carcinoma (uHCC) are often excluded from clinical trials due to adverse prognostic factors. The SIERRA (NCT05883644) study assesses the efficacy and safety of STRIDE (Single Tremelimumab Regular Interval Durvalumab) in clinically relevant subgroups of uHCC with poorer prognosis, including participants with more decompensated hepatic function, worse performance status, or more advanced disease than the HIMALAYA (NCT03298451) study. Methods: SIERRA is a phase 3b, single-arm, multicenter study that enrolled participants with uHCC with: Child-Pugh (CP) class of B7 or B8 with Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, without main trunk portal vein thrombosis (PVT) (CP B7/B8 cohort); CP class A with ECOG PS 2, without main trunk PVT (ECOG PS 2 cohort); or CP class A with ECOG PS 0-1 with evidence of chronic main trunk PVT (Vp4 cohort). Participants received STRIDE (tremelimumab 300 mg plus durvalumab 1,500 mg once followed by durvalumab 1,500 mg every 4 weeks). This preplanned early safety analysis occurred once ∼60 participants had been followed for ≥6 months (data cutoff: September 27, 2024). Co-primary endpoints are incidence of grade 3/4 adverse events (AEs) possibly related to study treatment (PRAEs) within 6 months of treatment initiation and objective response rate. The study is ongoing. Results: = 19). Median (Q1-Q3) number of cycles of durvalumab was 4.0 (2.0-8.0). Incidence of grade 3/4 PRAEs occurring within 6 months of treatment was 19.4% (95% confidence interval, 12.1-28.6) overall. Incidence of serious AEs was 32.7%. PRAEs, leading to death, occurred in 2.0% of participants. Conclusion: The safety profile of STRIDE was manageable and consistent with the HIMALAYA study in participants with poorer prognosis than in HIMALAYA.
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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 | 0.006 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".