Sintilimab Plus Bevacizumab Biosimilar Improved Response in Unresectable HCC

Zhenggang Ren

New findings from the ORIENT-32 trial suggest sintilimab plus a bevacizumab biosimilar (IBI305) was associated with significant improvements in response measures in patients with unresectable hepatocellular carcinoma (HCC).

Data from the trial suggest the use of sintilimab plus IBI305 improved objective response rate, time to response, duration of response, and depth of response, compared with sorafenib.

Led by Zhenggang Ren, Department of Hepatic Oncology, Zhongshan Hospital, Fudan University, the ORIENT-32 trial assessed the anti-PD-1 antibody plus a bevacizumab biosimilar (anti-VEGF antibody) versus sorafenib as a first-line treatment for unresectable HCC. The trial results reported the treatment demonstrated significant improvement in both overall survival and progression-free survival.

In the current report, Ren and colleagues laid out the updated results of objective response rate, time to response, duration of response, and depth of response. A total of 571 eligible patients with unresectable HCC were enrolled and randomized (2:1) to receive sintilimab (200 mg IV every 3 weeks [Q3W]) plus IBI305 (15 mg/kg IV Q3W) or sorafenib (400 mg orally, BID) until disease progression or unacceptable toxicity.

The investigator team evaluated tumors using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and HCC-modified RECIST (mRECIST). They additionally analyzed the four measures: objective response rate, time to response, duration of response, and depth of response.

The study defined depth of response as the minimum percentage of sum of longest diameter change and longest diameter change described as mean (standard deviation, SD). The data cutoff was the end of December 2021, and the median follow-up time was 26.7 months.

Data show the objective response rate in sintilimab plus IBI305 and sorafenib group was 21.0% (77 of 367) versus 4.7 (8 of 169) per RECIST 1.1 and 25.1% (92 of 367) versus 7.7% (13 of 169) per mRECIST.

Results additionally show the median time to response in sintilimab plus IBI305 was 2.8 (SD, 2.4 – 3.3) months per RECIST 1.1 and 2.6 (SD, 1.6 – 2.9) months per mRECIST. The median duration of response in sintilimab plus IBI305 was 20.3 months (SD, 12.3 – NE) months per RECIST 1.1.

Investigators additionally found the minimum percentage of sum of longest diameter change was larger in the sintilimab plus IBI305 arm than in the sorafenib arm (-13.4% vs. 3.2% per RECIST 1.1).

Similar data report the longest diameter change in the largest liver lesion also favored the sintilimab plus IBI305 arm (–27.6% vs. –11.5%), including larger tumors (≥7 cm; –21.2% vs. –9.9%) all per RECIST 1.1.

The study, “ORIENT-32: Updated characterization of response to sintilimab plus bevacizumab biosimilar (IBI305) vs. sorafenib for unresectable hepatocellular carcinoma,” was published in Journal of Clinical Oncology.