AZUR-2, a phase III, open-label, randomized study of perioperative dostarlimab monotherapy vs standard of care in previously untreated patients with T4N0 or stage III dMMR/MSI-H resectable colon cancer.

Abstract

TPS240 Background: Emerging evidence suggests neoadjuvant therapy may benefit patients (pts) with advanced colon cancer. Neoadjuvant immunotherapy has shown promising efficacy for early-stage mismatch repair deficient (dMMR) colon cancer [1,2]. Evidence from other immunogenic tumors suggests that a perioperative approach with immunotherapy may further improve survival outcomes [3,4]. Dostarlimab (anti-PD-1) has shown a favorable benefit:risk profile in previously untreated dMMR locally advanced rectal cancer [5] and in advanced dMMR/microsatellite instability-high (MSI-H) solid tumors [6]. AZUR-2 (NCT05855200) will evaluate the efficacy and safety of perioperative dostarlimab monotherapy vs standard of care (SOC) in pts with previously untreated T4N0 or Stage III dMMR/MSI-H resectable colon adenocarcinoma. Methods: AZUR-2 is a global, multicenter, randomized, open-label Phase III study. Approximately 711 pts will be enrolled. Key eligibility criteria include age ≥18 years, no prior therapy or surgery for colon cancer, ECOG PS 0–1, and no symptomatic bowel obstruction. Central prescreening is available at sites without local dMMR/MSI-H testing (not required if dMMR/MSI-H already determined). Pts stratified by clinical tumor/node (TN) staging will be randomized 2:1 to receive dostarlimab pre- and post-surgery, or surgery followed by SOC (adjuvant FOLFOX/CAPEOX for 3–6 months or watch and wait approach per physician’s discretion). Primary endpoint is event-free survival (EFS) (events: recurrence based on radiological assessment by blinded independent central review or pathological assessment of new lesions, disease progression precluding surgery, treatment (tx)-related toxicity precluding surgery, or death). Secondary endpoints include pathological response, OS, and safety. Disease assessments will consist of CT scans of chest, abdomen, and pelvis. Pts will undergo safety follow-up at end of tx and at 30 and 90 days after last dose. Efficacy will be assessed in all pts randomized (intent-to-treat) and safety in all pts who receive surgery or ≥1 dose of study tx. A stratified log-rank test will be used for primary analysis. The primary analysis for EFS with >90% power will be conducted after all pts have been followed for ≥3 years. An interim EFS analysis will be conducted ~12 months earlier. Exploratory endpoints include pt-reported outcomes to evaluate health-related quality of life.