Tremelimumab plus durvalumab safe as first-line treatment for uHCC patients

The use of single tremelimumab (T) regular interval durvalumab (D), or STRIDE, results in a manageable safety profile in Asian patients with unresectable hepatocellular carcinoma (uHCC), as shown by the preliminary results of the SIERRA study.

The ongoing phase IIIb SIERRA study is currently assessing the safety and efficacy of STRIDE as first-line treatment in a broader population with poorer prognoses than the HIMALAYA study. [NEJM Evid 2022;1:EVIDoa2100070]

“These results provide preliminary evidence for the safety profile of STRIDE in Asian patients with adverse uHCC prognosis, including those with worse hepatic function, poorer ECOG PS or more advanced vascular invasion than those who are typically included in clinical trials for uHCC,” said lead study author Dr Jung Yong Hong, Samsung Medical Center, Sungkyunwan University School of Medicine, Seoul, Korea.

SIERRA included patients with uHCC and any of the following: Child-Pugh (CP) B7 or B8 with ECOG PS 0–1 without main trunk portal vein thrombosis (PVT) (CP B7/B8 cohort), CP A with ECOG PS 2 without main trunk PVT (ECOG PS 2 cohort), or CP A with ECOG PS 0–1 with evidence of chronic main trunk PVT (Vp4 cohort) received T 300 mg plus D 1,500 mg on day 1, then D 1,500 mg monotherapy every 4 weeks.

Hong and his team then assessed the incidence of grade 3 or 4 adverse events (AEs) possibly related to study treatment (PRAEs) within 6 months of STRIDE initiation through 27 September 2024.

Forty-seven uHCC patients (median age 70.0 years) from Asia received STRIDE, with a median safety follow-up of 3.6 months in the CP B7/B8 cohort (n=16), 7.5 months in the ECOG PS 2 cohort (n=25), 5.4 months in the Vp4 cohort (n=6), and 6 months overall. [ESMO Asia 2025, abstract 273MO]

Of the Asian participants, 29 were from Korea, seven from Japan, four from Singapore, four from Hong Kong, and three from Vietnam.

Safety analysis

At 6 months following STRIDE initiation, the overall incidence of grade 3 or 4 PRAEs was 25.5 percent (95 percent confidence interval [CI], 13.9‒40.3). Of the patients, 93.6 percent reported any AEs, and 23.4 percent experienced serious AEs.

Pruritus (23.4 percent) was the most frequent PRAE, followed by aspartate aminotransferase increase (12.8 percent) and maculopapular rash (12.8 percent). Unfortunately, three AEs resulted in treatment discontinuation, and one led to death.

“These early safety results from the SIERRA study suggest that participants with uHCC recruited in Asia and treated with STRIDE had manageable side effects and similar side effects to the SIERRA global population,” Hong said. 

“It was too early to assess the percentage of participants who had a decrease in the size or number of tumours after treatment during this analysis,” he added.

In the full safety analysis involving 98 patients with uHCC, AEs were low and manageable at data cutoff. The incidence of grade 3 or 4 PRAEs within 6 months of STRIDE initiation occurred in 19 patients (19.4 percent, 95 percent CI, 12.1‒28.6), which was considered low.

“Historically, individuals with certain adverse prognostic factors have been excluded from HCC clinical trials to avoid heterogeneity,” Hong said. “Due to the lack of prospective clinical trial data, making treatment recommendations for this population of people with HCC is challenging.”

SIERRA treated participants with the STRIDE regimen until they experienced tumour growth, had side effects that caused them to discontinue treatment, wanted to leave the study, or died.