Abstract 448TiP
Background
A new concept of ‘NeoRAS wild-type (WT)’ which means conversion of RAS status from RAS mutant to RAS WT after treatment has been reported; previous studies demonstrated the potential efficacy of epidermal growth factor receptor (EGFR) inhibitors for metastatic colorectal cancer (mCRC) patients with NeoRAS WT. Moreover, it has been suggested that gene mutational status in circulating tumor DNA (ctDNA) may be useful to define the NeoRAS WT mCRC avoiding false negative of RAS mutation and gene mutations other than RAS in ctDNA are associated with efficacy of EGFR inhibitors.
Trial design
This C-PROWESS trial, is a multicenter, single-arm phase II trial to assess the efficacy and safety of panitumumab plus irinotecan in mCRC patients with NeoRAS WT. Key eligibility criteria include patients with initially proven RAS mutant mCRC refractory or intolerant to fluoropyrimidine, oxaliplatin, and irinotecan; RAS mutation negative in ctDNA defined as plasma mutant allele frequencies [MAF] of all RAS ≤ 0.1%) within 28 days prior to enrollment; and Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2. The primary endpoint is a response rate (RR) and the secondary endpoints are progression free survival, overall survival, and adverse events. Expecting a RR of 15% with a threshold set at 4% (one-sided α = 0.10; β = 0.2), the target sample size is 30 patients. Biomarker analyses is planned using next-generation sequencing-based ctDNA analysis (Guardant360) to explore the biomarkers identifying patients who would benefit from EGFR inhibitor among mCRC patients with NeoRAS WT.
Clinical trial identification
jRCT, s031210565. Registered date: 20 January, 2022.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
K. Yamaguchi: Financial Interests, Personal, Speaker’s Bureau: Daiichi-Sankyo. All other authors have declared no conflicts of interest.