Regorafenib plus nivolumab in unresectable hepatocellular carcinoma: the phase 2 RENOBATE trial

Regorafenib, exhibiting anti-tumor activity and potential immunomodulatory effects in unresectable hepatocellular carcinoma (uHCC), was combined with nivolumab in the phase 2 RENOBATE trial. Forty-two patients received the combination as front-line treatment. The primary endpoint (investigator-assessed objective response rate) was 31.0%. Common adverse events included palmar-plantar erythrodysesthesia syndrome, alopecia, and skin rash. Median progression-free survival was 7.38 months, and the 1-year overall survival rate was 80.5%. Single-cell RNA sequencing suggested that long-term responders showed T cell receptor repertoire diversification and other immune-related changes. The results support further development of this combination therapy.

Hyung-Don Kim, Seyoung Jung, Ho Yeong Lim, Baek-Yeol Ryoo, Min-Hee Ryu, Samuel Chuah, Hong Jae Chon, Beodeul Kang, Jung Yong Hong, Han Chu Lee, Deok-Bog Moon, Ki-Hun Kim, Tae Won Kim, David Tai, Valerie Chew, Jeong Seok Lee, Richard S. Finn, June-Young Koh, Changhoon Yoo