IMbrave050 Phase 3 Adjuvant HCC Trial Reaches Full Completion — OS Data Remain Immature

The second interim analysis of atezolizumab plus bevacizumab versus active surveillance in resected hepatocellular carcinoma shows an updated recurrence-free survival HR of 0.90 but an immature OS signal with a point estimate numerically favoring surveillance.

Science & Research Desk Saturday, 20 June 2026 · 2 min read

The IMbrave050 Phase 3 trial, evaluating atezolizumab plus bevacizumab as adjuvant therapy in high-risk hepatocellular carcinoma (HCC) after curative resection or ablation, has reached full completion following the second pre-planned interim analysis — with overall survival data remaining immature, and the OS point estimate numerically unfavorable to treatment.

IMbrave050 (NCT04102098) enrolled 668 patients with high-risk HCC, defined by pathological features including microvascular invasion, satellite nodules, or large tumor size, and randomized them one-to-one to atezolizumab 1,200 mg plus bevacizumab 15 mg/kg IV every three weeks for 12 months versus active surveillance. The study was the first large randomized Phase 3 trial of an immune checkpoint combination in the adjuvant HCC setting.

The first interim analysis, published in The Lancet in 2023 (Qin et al., Lancet 2023;402:1835–1847; DOI: 10.1016/S0140-6736(23)01796-8), reported a recurrence-free survival benefit for the combination arm, with OS data too early for analysis.

The second interim analysis, now published by Yopp and colleagues in the Journal of Hepatology (2026;84:1102–1111), shows an updated RFS hazard ratio of 0.90 (95% CI 0.72–1.12) — a point estimate still favoring the combination but no longer statistically significant. More critically, overall survival data remain immature: the OS hazard ratio at second interim is 1.26 (95% CI 0.85–1.87). That wide confidence interval does not exclude meaningful harm, does not confirm benefit, and reflects the relatively short follow-up relative to the natural history of resected HCC.

The numerical OS point estimate exceeding 1.0 — meaning more deaths in the treatment arm than in active surveillance at this interim — warrants caution in extrapolating the RFS finding to a net benefit conclusion. Mature OS remains the regulatory gold standard in oncology adjuvant trials; the current RFS estimate, no longer statistically significant, is insufficient alone to establish a favorable benefit-risk profile. Additional follow-up and OS maturity are required before the adjuvant role of atezolizumab-bevacizumab in HCC can be fully evaluated.

Yopp A, et al. IMbrave050 second interim. J Hepatol. 2026;84:1102–1111. Qin S, et al. Lancet. 2023;402:1835–1847. DOI: 10.1016/S0140-6736(23)01796-8.

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IMbrave050 second interim (Yopp et al., J Hepatol 2026;84:1102–1111) shows updated RFS HR 0.90 (95% CI 0.72–1.12) and immature OS (HR 1.26, 95% CI 0.85–1.87).

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The first interim analysis was published in The Lancet in 2023 (Qin et al., Lancet 2023;402:1835–1847, DOI 10.1016/S0140-6736(23)01796-8).

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IMbrave050 (NCT04102098) enrolled 668 patients with high-risk HCC after curative resection or ablation.

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After publication, a separate AI panel re-verifies every edition against these same sources. The running claim-confirmation rate and every correction are public on the accuracy ledger.