New Medicines

Advanced, unresectable hepatocellular carcinoma (HCC) - first-line with durvalumab


New molecular entity

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
May 22Filed in EU via centralised procedure [11].
Apr 22FDA accepts a biologics license application (BLA) from AstraZeneca and granted a priority review of tremelimumab as a single-dose added to durvalumab for treating first-line HCC [10].
Jul 21Filings based on HIMALAYA now not until H1 22 [8].
Jan 20Tremelimumab was granted orphan drug designation for treatment of hepatocellular carcinoma in the USA [2].


Human monoclonal antibody that blocks the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) contributing to T cell activation, priming the immune response to cancer and fostering cancer cell death [1].
Liver cancer is the third leading cause of cancer death and the sixth most commonly diagnosed cancer worldwide, with approximately 20% of patients alive five years after diagnosis. HCC represents about 80-90% of all primary liver cancers. Approximately 700,000 people were estimated to be diagnosed with HCC around the world in 2018. Between 80-90% of all patients with HCC also have chronic liver disease, which is primarily caused by infection with the hepatitis B or C viruses [1].
Advanced, unresectable hepatocellular carcinoma (HCC) - first-line with durvalumab

Further information


Trial or other data

Jan 22Company reports pts on tremelimumab + durvalumab had a 22% decrease in the risk of death vs compared to sorafenib. Median OS was 16.4 months vs 13.8 months for sorafenib. Combination also showed no increase in severe liver toxicity and fewer discontinuations due to treatment-related adverse events vs. sorafenib [9].
Nov 21PIII HIMALAYA is described as still recruiting, but states that collection of primary outcome data completed in Aug 21 [7].
Oct 21Tremelimumab and durvalumab demonstrated significant overall survival benefit vs sorafenib in PIII HIMALAYA trial. The combination showed a favourable safety profile [6].
Oct 20A randomised, open-label, multi-centre PIII trial (HIMALAYA; NCT03298451; EudraCT2016-005126-11), initiated Nov 2017, to evaluate the efficacy and safety of tremelimumab plus durvalumab combination therapy and durvalumab monotherapy versus sorafenib in the treatment of patients (n=1650 planned) with no prior systemic therapy for unresectable hepatocellular carcinoma, is no longer recruiting. Estimated primary completion date is Dec 2020 [2,3].
May 20AstraZeneca report results from an open-label, multicentre, global PII study (Study 22; NCT02519348). In the primary endpoint of the trial evaluating safety, all experimental arms demonstrated an acceptable profile and no new safety signals were identified. Patients treated with a single, priming dose of tremelimumab 300mg added to durvalumab every four weeks (T300+D regimen) achieved a median overall survival (OS) of 18.7 months in a key secondary endpoint. In other key secondary endpoints, objective response rate (ORR) confirmed by independent central review was 24% with the T300+D regimen, and median duration of response (DoR) was not yet reached at the time of data cut-off [1].