FDA Approves Tremelimumab in Combination with Durvalumab for Unresectable Hepatocellular Carcinoma

On 21 October 2022, the US Food and Drug Administration (FDA) approved tremelimumab (Imjudo, AstraZeneca Pharmaceuticals) in combination with durvalumab for adult patients with unresectable hepatocellular carcinoma (HCC).

Efficacy was evaluated in HIMALAYA (NCT03298451), a randomised (1:1:1), open-label, multicentre study in patients with confirmed unresectable HCC who had not received prior systemic treatment for HCC. Patients were randomised to one of three arms: tremelimumab 300 mg as a one-time single intravenous (i.v.) infusion plus durvalumab 1500 mg i.v. on the same day, followed by durvalumab 1500 mg i.v. every 4 weeks; durvalumab 1500 mg i.v. every 4 weeks; or sorafenib 400 mg orally twice daily until disease progression or unacceptable toxicity. This approval is based on a comparison of the 782 patients randomised to tremelimumab plus durvalumab to sorafenib.

The major efficacy outcome was overall survival (OS). Tremelimumab plus durvalumab demonstrated a statistically significant and clinically meaningful improvement in OS compared to sorafenib (stratified hazard ratio [HR] of 0.78, 95% confidence interval [CI] 0.66, 0.92; 2-sided p value = 0.0035); median OS was 16.4 months (95% CI 14.2, 19.6) versus 13.8 months (95% CI 12.3, 16.1).

Additional efficacy outcomes included investigator-assessed progression-free survival (PFS) and overall response rate (ORR) according to RECIST v1.1. Median PFS was 3.8 months (95% CI 3.7, 5.3) and 4.1 months (95% CI 3.7, 5.5) for the tremelimumab plus durvalumab and sorafenib arms, respectively (stratified HR 0.90; 95% CI 0.77, 1.05). ORR was 20.1% (95% CI 16.3, 24.4) in the tremelimumab plus durvalumab arm and 5.1% (95% CI 3.2, 7.8) for those treated with sorafenib.

The most common (≥20%) adverse reactions occurring in patients were rash, diarrhoea, fatigue, pruritis, musculoskeletal pain and abdominal pain.

The recommended tremelimumab dose for patients weighing 30 kg or more is 300 mg i.v. as a single dose in combination with durvalumab 1500 mg at Cycle 1/Day 1, followed by durvalumab 1500 mg i.v. every 4 weeks. For those weighing less than 30 kg, the recommended tremelimumab dose is 4 mg/kg i.v. as a single dose in combination with durvalumab 20 mg/kg i.v., followed by durvalumab 20 mg/kg i.v. every 4 weeks.

Full prescribing information for Imjudo is available here.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

Tremelimumab was granted orphan drug designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA’s Oncology Center of Excellence Project Facilitate.