The US Food and Drug Administration (FDA) has approved Imjudo (tremelimumab-actl) in combination with durvalumab for the treatment of adults with unresectable hepatocellular carcinoma (HCC).

Imjudo is a human monoclonal antibody that targets the activity of CTLA-4. The novel dose and schedule of the combination (the STRIDE regimen [Single Tremelimumab Regular Interval Durvalumab]) includes a single priming dose of tremelimumab via intravenous infusion added to durvalumab (Imfinzi), a PD-L1 blocking antibody, followed by durvalumab every 4 weeks.

The approval was based on data from the open-label, phase 3 HIMALAYA trial (ClinicalTrials.gov Identifier: NCT03298451), which was designed to evaluate the efficacy and safety of tremelimumab plus durvalumab as first-line treatment in adults with unresectable HCC. Patients received a single priming dose of tremelimumab at 300 mg added to durvalumab at 1500 mg (n=393) followed by durvalumab every 4 weeks vs sorafenib (n=389). The primary endpoint was overall survival.


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Results showed that patients treated with the STRIDE regimen experienced a 22% reduction in the risk of death vs sorafenib (hazard ratio [HR], 0.78, 95% CI 0.66-0.92; P =.0035). Median overall survival was reported to be 16.4 months (95% CI, 14.2-19.6) for the STRIDE group compared with 13.8 months (95% CI, 12.3-16.1) for the sorafenib group.

The objective response rate was 20.1% with STRIDE and 5.1% with sorafenib. The median duration of response was 22.3 months and 18.4 months, respectively. Nearly 31% of STRIDE-treated patients were still alive at 3 years vs 20% of those who received sorafenib.

No new safety signals were identified during the trial. The most common adverse reactions reported were rash, diarrhea, fatigue, pruritus, musculoskeletal pain, abdominal pain, increased AST/ALT, decreased hemoglobin, decreased sodium, increased bilirubin, increased alkaline phosphatase, and decreased lymphocytes. 

“Patients with unresectable liver cancer are in need of well-tolerated treatments that can meaningfully extend overall survival,” said Ghassan Abou-Alfa, MD, an attending physician at Memorial Sloan Kettering Cancer Center in New York, New York, and principal investigator of the HIMALAYA trial. “In addition to this regimen demonstrating a favorable 3-year survival rate in the HIMALAYA trial, safety data showed no increase in severe liver toxicity or bleeding risk for the combination, important factors for patients with liver cancer who also have advanced liver disease.”

Imjudo is supplied as 25 mg/1.25 mL and 300 mg/15 mL solution in single-dose vials. The product is expected to be available in early November 2022.

References

  1. Imjudo (tremelimumab) in combination with Imfinzi approved in the US for patients with unresectable liver cancer. News release. AstraZeneca. Accessed October 24, 2022. https://www.astrazeneca.com/media-centre/press-releases/2022/imfinzi-and-imjudo-approved-in-advanced-liver-cancer.html
  2. Imjudo. Package insert. AstraZeneca; 2022. Accessed October 24, 2022. https://den8dhaj6zs0e.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/0102c6fd-de8a-4b43-afa3-2a2c2115d472/0102c6fd-de8a-4b43-afa3-2a2c2115d472_viewable_rendition__v.pdf

This article originally appeared on MPR