Randomized Parallel-Group Phase II Study (NEOTERIC) of Atezolizumab With or Without Tiragolumab After Neoadjuvant...

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.