Randomized phase 2 trial of atezolizumab with or without tiragolumab after neoadjuvant chemoradiotherapy in locally advanced rectal cancer

Neoadjuvant chemoradiotherapy (nCRT) is the standard treatment for patients with locally advanced rectal cancer (LARC); however, pathologic complete response (pCR) rates and long-term outcomes remain suboptimal. Thephase 2 NEOTERIC trial, at five centers in China,evaluated atezolizumab (Atezo) with or without tiragolumab (Tira) after nCRT in patients with LARC. Patients (cT3N+M0 or cT4NanyM0) received long-course nCRT followed by three 21-day cycles of Atezo + Tira (n=28) or Atezo (n=27). Radical surgery was performed 2 weeks after final dose. The primary endpoint was pCR rate. The pCR rate was 35.7% 9(5% CI 18.6-55.9) in the Atezo + Tira group, which was significantly higher than the historical control rate of 15% (p=0.002), while the pCR rate in the Atezo group was 22.7% (8.6-42.3), showing a numerical improvement compared with the historical control rate of 15% (p=0.293). After a mediane follow-up of 21.55 months (ragen 20.67-22.24) the 1-year events-free survival rates were 96.3% in the Atezo + Tira group and 92.1% in the Atezo group. Grade 3 to 4 treatment-related adverse events occurred in 31.0% and 26.9%, respectively. No treatment-emergent deaths were reported. The authors conclude that in patients with LARC, Atezo + Tira after nCRT improved the pCR rate compared with historical controls, with an acceptable safety profile.