JAMA Netw Open

Dual immunotherapy shows promise when added to chemoradiation in rectal cancer

August 26, 2025

Dual immune checkpoint inhibitor (ICI) therapy with chemoradiotherapy (CRT) was safe and feasible, even in microsatellite-stable tumors traditionally resistant to immunotherapy. Although response rates were not significantly improved, the regimen showed clinical activity and supports further investigation into optimizing timing, dosing, and patient selection for immunoradiotherapy combinations.

Study details: The CHINOREC multicenter, phase 2, randomized trial (NCT04124601) was conducted in Austria from 2020 to 2024. Eighty patients with locally advanced, microsatellite-stable rectal cancer were randomized to receive standard neoadjuvant CRT with capecitabine and 50 Gy radiation, either alone or combined with sequential ipilimumab (1 mg/kg on day 7) and nivolumab (3 mg/kg every 2 weeks starting day 14). Surgery followed 10 to 12 weeks post-treatment.

Results: Adding ipilimumab and nivolumab to CRT didn’t increase surgical complications (77% in both groups; P>.99) or reoperation rates (8% vs. 7%; P>.99). Pathologic complete response rates were 30% in the CRT group and 22% in the CRT+ICI group (P=.44), while major pathologic response rates were nearly identical (38% vs. 37%; P>.99).

Source:

Laengle J, et al. (2025, August 22). JAMA Netw Open. Dual Immune Checkpoint Inhibition Plus Neoadjuvant Chemoradiotherapy in Rectal Cancer: A Randomized Clinical Trial. https://pubmed.ncbi.nlm.nih.gov/40844778/