局所進行直腸癌に対する術前化学放射線療法後のアテゾリズマブ単独またはチラゴルマブ併用（NEOTERIC試験）のランダム化並行群第II相試験

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. This study evaluated the safety and efficacy of atezolizumab (Atezo) with or without tiragolumab (Tira) after nCRT in patients with LARC.

This randomized, parallel-group, phase II study included a safety run-in and a subsequent randomized phase. Eligible patients (cT3N+M0 or cT4NanyM0) received long-course nCRT (45-50.4 Gy in 25-28 fractions with concurrent capecitabine), followed by three 21-day cycles of Atezo (1,200 mg once on day 1 of each cycle), either combined with Tira (600 mg; Atezo + Tira arm) or alone (Atezo arm). Radical surgery was performed 2 weeks after final dose. The primary end point was pCR rate. Secondary end points included 1-year event-free survival (EFS) rate and safety. Outcomes were compared with historical controls.

At data cutoff (January 6, 2025), three patients were enrolled in safety run-in and received Atezo + Tira. In randomized phase, 55 patients were assigned 1:1 to Atezo + Tira arm (n = 28) or Atezo arm (n = 27). pCR rate was 35.7% (95% CI, 18.6 to 55.9; v historical control [15%] P = .002) in Atezo + Tira arm and 22.2% (95% CI, 8.6 to 42.3; v historical control [15%] P = .293) in Atezo arm. After a median follow-up of 21.55 months (range, 20.67-22.24), 1-year EFS rates were 96.3% (95% CI, 76.5 to 99.5) in Atezo + Tira arm and 92.1% (95% CI, 72.1 to 98.0) in Atezo arm. Grade 3 to 4 treatment-related adverse events occurred in 31.0% and 26.9%. Grade 3 to 4 AEs related to Atezo or Tira were 10.3% and 11.5%, respectively. No treatment-emergent deaths were reported.

In patients with LARC, Atezo + Tira after nCRT statistically improved the pCR rate compared with historical controls, with an acceptable safety profile.