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

## TL;DR

This trial tests if giving immunotherapy before surgery improves outcomes for colorectal cancer patients with liver metastases.

## Contribution

The study is the first to evaluate preoperative atezolizumab and tiragolumab in colorectal liver metastases.

## Key findings

- The trial assesses tumor regression and surgical outcomes after preoperative immunotherapy.
- Immune biomarkers like tumor mutational burden and immune cell infiltration are explored for treatment response.
- Safety and feasibility of the drug combination before surgery are key evaluation points.

## Abstract

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.

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.

•The impact of preoperative combination immunotherapy on colorectal liver metastases is evaluated.•The feasibility and safety of atezolizumab and tiragolumab before surgery are assessed.•Biomarkers associating with treatment response are explored.

The impact of preoperative combination immunotherapy on colorectal liver metastases is evaluated.

The feasibility and safety of atezolizumab and tiragolumab before surgery are assessed.

Biomarkers associating with treatment response are explored.