FDA Grants Priority Review to Tremelimumab for Unresectable HCC

Tremelimumab’s biologics license application was accepted by the FDA and was given priority review, further supporting the use of a single priming dose of anti-CTLA4 plus durvalumab in unresectable hepatocellular carcinoma.

A biologics license application (BLA) for tremelimumab for the treatment of patients with unresectable hepatocellular carcinoma (HCC) was accepted and granted priority review from the FDA was based on results from the phase 3 HIMALAYA trial (NCT03298451), according to a press release from AstraZeneca; additionally, a supplemental BLA for durvalumab (Imfinzi) in the same indication was submitted.1

The combination utilizes a novel dose and schedule known as the Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen. The FDA has set the Prescription Drug User Fee Act date for the fourth quarter of 2022 per the use of the priority review voucher.

“The HIMALAYA trial showed an unprecedented 3-year overall survival [OS] in this setting with a single priming dose of tremelimumab added to [durvalumab], highlighting the potential for this regimen to improve longer-term survival outcomes. Patients with advanced liver cancer are in great need of new treatment options, and we are working closely with the FDA to bring this novel approach to patients in the US as soon as possible,” Susan Galbraith, executive vice president of Oncology R&D at AstraZeneca, said in a press release.

According to findings from the HIMALAYA trial, a single priming dose of tremelimumab plus durvalumab every 4 weeks reduced the risk of death by 22% compared with sorafenib (Nexavar; HR, 0.78; 96.02% CI, 0.65-0.93; P = .0035).2 Moreover, the median OS was 16.4 months in the tremelimumab arm compared with 13.8 in the sorafenib arm. Investigators estimated that 31% of patients were alive at 3 years compared with 20% in the tremelimumab and sorafenib arms, respectively.

The objective response rates in the tremelimumab and durvalumab arms were 20.1% and 5.1%, respectively. The STRIDE regimen also yielded a median duration of response of 22.3 months compared with 18.4 months in control arm. Severe liver toxicities did not increase with the addition of tremelimumab to durvalumab.

Durvalumab was assessed as a single agent in the study, with investigators reporting OS non-inferiority compared with sorafenib (HR, 0.86; 95.67% CI, 0.73-1.03; non-inferiority margin, 1.08). The median OS between the 2 arms was 16.6 months vs 13.8 months, respectively. Durvalumab also appeared to be better tolerated than sorafenib.

The combination was granted an orphan drug designation for patients with HCC in January 2020, and durvalumab is being developed for other liver indications, including for locoregional disease and as an adjuvant treatment.

References

  1. Tremelimumab accepted under priority review in the US for patients with unresectable liver cancer in combination with Imfinzi. News release. AstraZeneca. April 25, 2022. Accessed April 25, 2022. https://bit.ly/3k82xYr
  2. Imfinzi plus tremelimumab demonstrated unprecedented survival in 1st-line unresectable liver cancer with 31% of patients alive at three years. News release. AstraZeneca. January 18, 2022. Accessed January 18, 2022. https://bit.ly/3rRNF4J