Ghassan K. Abou-Alfa, MD
Investigators are looking into a combination of immunotherapy agents for patients with unresectable hepatocellular carcinoma (HCC), for whom there are limited treatment options in the first line. Researchers think the combination of durvalumab (Imfinzi), a PD-L1 inhibitor, and tremelimumab, a CTLA-4 inhibitor, may be the answer to this clinical need.
Figure. Durvalumab Plus Tremelimumab in First-Line Unresectable HCC
Prior studies have demonstrated that durvalumab and tremelimumab are active in HCC. Patients who are eligible for the HIMALAYA phase III trial must have had no prior systemic therapy for HCC and have an ECOG performance status of 0 or 1. “This is a population that you care for by using systemic therapy, because there are no other eligible things they can do. They are not eligible for surgeries or local therapy, and as such, they need something that will take care of their disease,” said Ghassan K. Abou-Alfa, MD, medical oncologist and principal investigator for the trial at Memorial Sloan Kettering Cancer Center in New York, New York.
“The combination has shown a clear synergy. The anti-CTLA-4 drug will work actively on some of the immune molecules in the lymph nodes and further promote activity of the anti-PD-1 drug, which will affect the tumor itself,” Abou-Alfa explained. “There is a very pure science that tells us that this is, by definition, a more efficient way of getting the response that we are looking for.”
Early Efficacy Data
In a prior, phase I/II study, 40 patients with HCC were evaluable to assess the safety and tolerability of the drug combination. The confirmed ORR was 17.5%, with 7 patients having a partial response. The ORR on the basis of confirmed and unconfirmed response was 25% (10/40 patients). The median time to response was 8 weeks (range, 7.6-24.0 weeks).6
The 2 drugs are being developed by AstraZeneca, based in Wilmington, Delaware.
- Hepatobiliary cancers version 4.2017. NCCN clinical practice guidelines in oncology. National Comprehensive Cancer Network. nccn.org/ professionals/physician_gls/pdf/hepatobiliary.pdf. Published October 9, 2017. Accessed January 17, 2018.
- FDA expands use of Stivarga to treat liver cancer [press release]. Silver Spring, MD: US Food and Drug Administration; April 27, 2017. fda. gov/NewsEvents/Newsroom/PressAnnouncements/ucm555608. htm. Accessed January 17, 2018.
- FDA grants accelerated approval to nivolumab for HCC previously treated with sorafenib [press release]. Silver Spring, MD: US Food and Drug Administration; September 22, 2017. fda.gov/Drugs/ InformationOnDrugs/ApprovedDrugs/ucm577166.htm. Accessed January 17, 2018.
- Durvalumab (MEDI4736, IMFINZI). NIH Division of Cancer Treatment and Diagnosis website. https://nciformulary.cancer.gov/available_ agents/Durvalumab.htm/. Updated June 30, 2017. Accessed January 17, 2018.
- Tremelimumab (CP-675,206). NIH Division of Cancer Treatment and Diagnosis website. https://nciformulary.cancer.gov/available_agents/ Tremelimumab.htm. Updated June 30, 2017. Accessed January 17, 2018.
- Kelley RK, Abou-Alfa GK, Bendell JC, et al. Phase I/II study of durvalumab and tremelimumab in patients with unresectable hepatocellular carcinoma (HCC): phase I safety and efficacy analyses. Presented at: 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, IL. Abstract 4073. https://meetinglibrary.asco.org/record/147423/abstract.
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