FDA Approves Tremelimumab Plus Durvalumab for Unresectable Hepatocellular Carcinoma

On October 21, 2022, The US Food and Drug Administration (FDA) approved tremelimumab plus durvalumab for adult patients with unresectable hepatocellular carcinoma.

This approval was based on the results of the randomized, open-label, multicenter, phase 3 HIMALAYA study. Patients with unresectable hepatocellular carcinoma who had not previously received systemic therapy for hepatocellular carcinoma were randomized on a 1:1:1 basis to receive 300 mg tremelimumab intravenously once plus 1500 mg durvalumab intravenously on that same day followed by the same dose of durvalumab every 4 weeks; 1500 mg durvalumab intravenously every 4 weeks; or 400 mg sorafenib orally twice daily.

Patients continued treatment until disease progression or unacceptable tolerability. The primary outcome was overall survival (OS), with secondary outcomes including progression-free survival (PFS) and overall response rate (ORR).

The median OS of the tremelimumab plus durvalumab arm was 16.4 months (95% confidence interval [CI], 14.2 to 19.6), compared to 13.8 months (95% CI, 12.3 to 16.1) in the sorafenib arm. This represented a statistically significant and clinically meaningful improvement with tremelimumab plus durvalumab (stratified hazard ratio [HR], 0.78; 95% CI, 0.66 to 0.92; two-sided P = .0035). The median PFS of the tremelimumab plus durvalumab arm compared to the sorafenib arm was 3.8 months (95% CI, 3.7 to 5.3) vs 4.1 months (95% CI, 3.7 to 5.5), respectively (stratified HR, 0.90; 95% CI, 0.77 to 1.05. For those patients treated with tremelimumab plus durvalumab, the ORR was 20.1% (95% CI, 16.3 to 24.4), compared to 5.1% (95% CI, 3.2 to 7.8) for those treated with sorafenib.

The most common adverse event, occurring in ≥20% of patients, were rash, diarrhea, fatigue, pruritis, musculoskeletal pain, and abdominal pain.

Source:

FDA approves tremelimumab in combination with durvalumab for unresectable hepatocellular carcinoma. United States Food and Drug Administration. October 24, 2022. Accessed October 24, 2022. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tremelimumab-combination-durvalumab-unresectable-hepatocellular-carcinoma