FDA approved the STRIDE combination for non-resectable hepatocellular carcinoma (HCC) on October 21, 2022. The indication for the addition of single dose tremelimumab on the basis of duvalilizumab for treatment of unresectable hepatocellular carcinoma has been prioritized by the FDA license in April this year. This approval is based on data from the HIMALAYA Phase 3 trial, and its latest results were published at the 2022 ESMO Conference. The results showed that in the front-line environment of patients with unresectable hepatocellular carcinoma, the STRIDE regimen significantly improved overall survival (OS) regardless of baseline albumin-bilirubin (ALBI) grade compared with sorafenib (Nexavar).
About HIMALAYA Phase 3 Trial
HIMALAYA is an open-label, multi-center, global phase 3 trial that recruits confirmed unresectable HCC patients. The patient requested ECOG to be present with 0 or 1, Child-Pugh grade A, without any systemic treatments before, and without portal venous thrombosis in . A total of 1324 patients were included in
. All patients were randomly treated with STRIDE regimen, duvalilizumab monotherapy and sorafenib. The STRIDE regimen was given 300 mg tremelimumab 1 dose and 1500 mg valafolizumab (n=393), the STRIDE group was given the same dose and cycle monotherapy as the STRIDE group (n=389), and the sorafenib group was given 400 mg sorafenib twice daily dose (n=389).
The main goal of this trial is the STRIDE protocol with sorafenib OS, and the key secondary goal is the OS of durvalumab monotherapy and sorafenib monotherapy. Additional secondary goals include progression-free survival (PFS), objective response rate (ORR), time to remission (DOR) per investigator evaluated, and RECIST v1.1 standard, and security.
In patients with grade 1 ALBI, the median survival of the STRIDE regimen was 23.43 months (95% CI, 19.19-28.75), while the median survival of sorafenib was 19.02 months (95% CI, 15.67-23.16) (HR, 0.79; 95% CI, 0.62-1.01). In patients with grade 2/3 ALBI, the median OS for the STRIDE regimen was 11.30 months (95% CI, 9.33-14.19), while the median OS for sorafenib was 9.72 months (95% CI, 7.23-11.76) (HR, 0.83; 95% CI, 0.65 - 1.05).
In addition, monopharmaceutical valizumab produced good OS results regardless of ALBI grade compared to sorafenib. In patients with Grade 1 ALBI, the median survival of duvalilizumab was 21.16 months (95% CI, 17.38-25.86), while the median survival of sorafenib was 19.02 months (95% CI, 15.67-23.16) (HR, 0.91; 95% CI, 0.71-1.15). In patients with grade 2/3 ALBI, the median survival of duvalilizumab was 12.29 months (95% CI, 9.30-16.03) and the median survival of sorafenib was 9.72 months (95% CI, 7.23-11.76) (HR, 0.87; 95% CI, 0.69-1.09).
Regarding safety, the toxicity characteristics of the STRIDE regimen and the single agent durvalumab were proven to be consistent with the previously reported toxicity characteristics. No new safety signals were observed. 97.4% of patients who received the STRIDE regimen experienced any level of toxicity, compared with 88.9% of patients who received the single-agent durvalumab and 95.5% of patients who received sorafenib. Treatment-related adverse reactions (AEs) were experienced in 75.8%, 52.1% and 84.8% of patients, respectively. Grade 3 or grade 4 toxicity was reported in 50.5%, 37.1% and 52.4% of patients, respectively; 25.8%, 12.9% and 36.9% of patients, respectively, experienced treatment-related grade 3 or grade 4 toxicity.
About dual immunization combined with
This protocol is the first approved anti-PD-L1 and anti-CTLA4 antibody combination protocol in the HCC field, and has acceptable and controllable toxicity. The STRIDE regimen is significantly better than sorafenib, and the Kaplan-Meier curve shows that its 3-year survival rate is 30.7%. In terms of ORR, OS and CR rates, the STRIDE regimen is also better than the single-druvalumab, which shows that a single dose of high-dose anti-CTLA4 antibody has a significant additional effect on the anti-PD-L1 antibody.Another study of a combination of anti-PD-L1 and anti-CTLA4 antibody protocols in the field of hepatocytes is also underway. According to the 5-year data from the Phase 1/2 CheckMate 040 trial, a dual immunotherapy combination composed of nivolumab (Opdivo) administered at 1 mg/kg and ipilimumab (Yervoy) administered at 3 mg/kg provides lasting response and long-term survival benefits for patients with advanced HCC after sorafenib treatment. In March 2020, the FDA approved the accelerated review of nivolumab plus ipilimumab in March 2020, based on early data from CheckMate 040, for the treatment of HCC patients who had previously received sorafenib.
Source: International Liver and Gallbladder Information
