Benzinga | Jan 19, 2022 04:54AM EST

AstraZeneca Announced MFINZI (durvalumab) Plus Tremelimumab Demonstrated Unprecedented Survival in 1st-line Unresectable Liver Cancer With 31% of Patients Alive at Three Years

nificant and clinically meaningful improvement in overall survival (OS) versus sorafenib as a 1st-line treatment for patients with unresectable hepatocellular carcinoma (HCC) who had not received prior systemic therapy and were not eligible for localised treatment.

This novel dose and schedule of Imfinzi and tremelimumab, an anti-CTLA4 antibody, is called the STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab). Results from the trial will be presented on 21 January at the 2022 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.

Liver cancer, of which HCC is the most common type, is the third-leading cause of cancer death and the sixth most commonly diagnosed cancer worldwide.1,2 Approximately 80,000 people in the US, Europe and Japan and 260,000 people in China present with advanced, unresectable HCC each year.3 Only 7% of patients with advanced disease survive five years.4

Ghassan Abou-Alfa, MD, MBA, Attending Physician at Memorial Sloan Kettering Cancer Center and principal investigator in the HIMALAYA Phase III trial, said: "Patients with unresectable liver cancer face a dismal prognosis, and new treatment options are critical to improving long-term survival. The three-year overall survival rate and favourable safety profile seen with the STRIDE regimen set a new benchmark in this setting and underscore the potential of this innovative treatment approach."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "The HIMALAYA trial reinforces our scientific approach for tremelimumab, tapping into the potential of CTLA-4 inhibition and a unique dosing regimen to prime the immune system to help patients live longer and with minimal side effects. We look forward to bringing potential new treatment options to patients with unresectable liver cancer, an area of high unmet need, as quickly as possible."

Patients treated with the STRIDE regimen experienced a 22% reduction in the risk of death versus sorafenib (based on a hazard ratio [HR] of 0.78, 96.02% confidence interval [CI] 0.65-0.93; p=0.0035). Median OS was 16.4 months versus 13.8 for sorafenib. An estimated 31% of patients were still alive at three years versus 20% for sorafenib.

Results also showed an increase in objective response rate (ORR) with the STRIDE regimen versus sorafenib (20.1% vs. 5.1%). Median duration of response (DoR) was 22.3 months with the STRIDE regimen versus 18.4 with sorafenib. The addition of tremelimumab to Imfinzi did not increase severe liver toxicity, and no bleeding risk was observed.

HIMALAYA also tested Imfinzi monotherapy, which demonstrated non-inferior OS to sorafenib (HR 0.86; 95.67% CI 0.73-1.03; non-inferiority margin 1.08) with a median OS of 16.6 months versus 13.8, and an improved tolerability profile versus sorafenib.

Summary of efficacy resultsi:

STRIDE regimen(n=393) Imfinzi monotherapy (n=389) Sorafenib(n=389)OSii,iii Number of patients with event (%) 262 (67) 280 (72) 293 (75)Median OS (95% CI) (in months) 16.4 16.6 13.8Hazard ratio (96.02% CI) p-value 0.78 (0.65, 0.93)0.0035OS rate at 24 months (%) 40.5 39.6 32.6OS rate at 36 months (%) 30.7 24.7 20.2ORR (%) 20.1 17.0 5.1Median DoR (months) 22.3 16.8 18.4Analysis was done at 71% maturityInvestigator-assessed OS data cut-off date was 27 August 2021Median (range) follow-up durations at data cut-off: 33.18 (31.74-34.53), 32.56 (31.57-33.71) and 32.23 (30.42-33.71) months for STRIDE regimen, Imfinzi monotherapy and sorafenib, respectively.The safety profiles of the STRIDE regimen and for Imfinzi alone were consistent with the known profiles of each medicine, and no new safety signals were identified. Grade 3 or 4 treatment-related adverse events (AEs) were experienced by 25.8% of patients treated with the STRIDE regimen and by 12.9% of patients treated with Imfinzi alone, versus 36.9% of patients on sorafenib.

Incidence of Grade 3 or 4 treatment-related hepatic events were low across treatment arms (5.9% for the STRIDE regimen and 5.2% for Imfinzi, versus 4.5% for sorafenib). Treatment-related AEs led to treatment discontinuation in 8.2% of patients treated with the STRIDE regimen and 4.1% of patients treated with Imfinzi alone, versus 11% for sorafenib.

An additional presentation featured during the ASCO Gastrointestinal Cancers Symposium will showcase Imfinzi data from the TOPAZ-1 Phase III trial, demonstrating the potential of this medicine in the treatment of advanced biliary tract cancer.