Preoperative immunotherapy with atezolizumab and tiragolumab in patients with colorectal liver metastases—the PURPLE trial

Background

In colorectal cancer (CRC), the liver is the most common site of metastasis, which is the leading cause of CRC-related mortality. Hepatic resection offers long-term survival in some patients with CRC liver metastases (CRLM), but recurrence rates remain high (50%-75% within 2 years). Preoperative immunotherapy may induce tumor regression and improve long-term surgical outcomes. The PURPLE trial evaluates the feasibility, safety, and efficacy of short-term preoperative immunotherapy with the anti-programmed death-ligand 1 (PD-L1) antibody atezolizumab and the anti-T cell immunoreceptor with Ig and ITIM domains (TIGIT) antibody tiragolumab in patients with resectable CRLM.

Study design

PURPLE is an international, open-label, multicenter, randomized phase II ‘window of opportunity’ trial. Patients with resectable CRLM are randomized 2 : 1 to receive two cycles of atezolizumab (840 mg) plus tiragolumab (420 mg) before surgery (experimental arm) or immediate surgery (control arm). The primary endpoint is the percentage of patients with complete or major pathological regression of the resected metastases (tumor regression grade 1/2, Rubbia-Brandt criteria). The statistical design follows Simon’s two-stage approach with interim and final analyses comparing pathological response rates using descriptive and exploratory methods. Secondary endpoints include feasibility, safety, post-operative complications, and metabolic response by positron emission tomography. Exploratory studies characterize immune cell infiltration, tumor mutational burden, and circulating tumor DNA dynamics.