A phase 2 multicenter, open-label, randomized, controlled trial in patients with stage II/III colorectal cancer who are ctDNA positive following resection to compare efficacy of autogene cevumeran versus watchful waiting.

Abstract

TPS3641 Background: Colorectal cancer (CRC) is one of the most commonly occurring cancers with high recurrence and mortality rate. Circulating tumor DNA (ctDNA) can be used as a marker of minimal residual disease after completion of surgical resection of stage II/III CRC, where detectable ctDNA levels (positive) post-AdCTx are associated with an increased risk of disease recurrence and novel therapies are needed. Autogene cevumeran is an investigational individualized neoantigen-specific immunotherapy that is designed to harness an immune response against patient-specific, tumor neoantigens. This clinical trial is in progress in patients with Stage II (high risk) / Stage III colorectal cancer who are ctDNA positive following resection. Methods: Autogene cevumeran is being evaluated in an open-label, Phase 2, randomized, controlled trial in patients with Stage II / III CRC patients who are ctDNA positive following resection. Patients are randomized to adjuvant therapy followed by autogene cevumeran compared to adjuvant therapy followed by watchful waiting. The primary endpoint is disease-free survival (DFS). The trial has a Biomarker Cohort of 15 patients who will receive autogene cevumeran irrespective of the ctDNA status to pursue exploratory objectives. The main study of the phase 2 trial consists of a randomized (1:1) design comparing the experimental arm (autogene cevumeran) with the observational arm (watchful waiting) in ctDNA positive CRC patients. A third Exploratory Cohort explores the efficacy and safety of autogene cevumeran in ctDNA positive CRC patients with early recurrence/relapse during or after completion of AdCTx. Patients enrolled onto the experimental group, the biomarker and exploratory cohorts will receive autogene cevumeran 6x q1w, followed by 2x q2w, followed by 7 “booster” doses q6w, to receive a total of 15 doses (dosed at 25μg). AEs are assessed according to CTCAE v5. DFS will be determined by an independent central radiology assessment. Key eligibility criteria include 1) Patients must have stage II/III rectal cancer or stage II (high risk)/III colon cancer that has been surgically resected (R0 confirmed by pathology report); 2) patients must be ctDNA positive following resection; and 3) at least 5 tumor neoantigens must be identified in the provided tumor sample for autogene cevumeran manufacturing (RNA lipoplex, RNA-LPX). ClinicalTrials.gov identifier: NCT04486378.