REMARRY and PURSUIT trials: liquid biopsy-guided rechallenge with anti-epidermal growth factor receptor (EGFR) therapy with panitumumab plus irinotecan for patients with plasma RAS wild-type metastatic colorectal cancer
Open Access
- 7 June 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in BMC Cancer
- Vol. 21 (1), 1-6
- https://doi.org/10.1186/s12885-021-08395-2
Abstract
Background: Previous clinical trials have demonstrated the potential efficacy of rechallenge with anti- epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) for patients with RAS/BRAF V600E wild-type metastatic colorectal cancer (mCRC). Moreover, post hoc biomarker analyses of clinical trials has suggested that RAS status in circulating tumor DNA (ctDNA) has a high probability to select patients who could benefit from anti-EGFR mAb rechallenge. Methods: This trial is composed of 2 phases: a monitoring phase (REMARRY) and a trial phase (PURSUIT). A monitoring phase, the REMARRY study, aims to evaluate the dynamics of plasma RAS status during the subsequent treatments after refractory to anti-EGFR therapy in patients with mCRC with RAS/BRAF V600E wild-type tumors who have progressed after a response to previous anti-EGFR therapy, using a highly sensitive digital polymerase chain reaction OncoBEAM RAS CRC kit in a central laboratory (Sysmex, Japan). A trial phase, the PURSUIT trial, is a multicenter, single-arm phase II trial to assess the efficacy and safety of rechallenge therapy with panitumumab plus irinotecan in patients without RAS mutations in ctDNA (plasma RAS negative) in the REMARRY study. Key eligibility criteria of the PURSUIT trial include RAS/BRAF V600E wild-type mCRC in tumor tissue refractory or intolerant to fluoropyrimidine, oxaliplatin, and irinotecan; progression after complete or partial response to previous anti-EGFR therapy; plasma RAS negative (defined as plasma mutant allele frequencies [MAF] of all RAS ≤ 0.1%) within 28 days prior to enrollment; 4 months or more between the last administration of previous anti-EGFR mAb and the start of protocol treatment; and Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 1. The primary endpoint is the confirmed objective response rate (ORR). The target sample size of the PURSUIT trial is 50 patients. Biomarker analyses will be performed in parallel using the OncoBEAM RAS CRC kit and a next-generation sequencing-based ctDNA analysis (Guardant360). Discussion: Our trial aims to confirm the clinical benefit of anti-EGFR mAb rechallenge therapy in patients with plasma RAS negative. Moreover, through biomarker analyses, our trial will shed light on which patients would benefit from rechallenge in addition to being plasma RAS negative. Trial registration: The REMARRY study: UMIN, UMIN000036424. Registered date: April 5, 2019. The PURSUIT trial: jRCT, jRCTs031190096. Registered date: October 1, 2019.Keywords
Funding Information
- Sysmex
- Takeda Pharmaceutical Company
This publication has 28 references indexed in Scilit:
- Panitumumab–FOLFOX4 Treatment and RAS Mutations in Colorectal CancerThe New England Journal of Medicine, 2013
- Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trialThe Lancet Oncology, 2013
- The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancersNature, 2012
- Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancerNature, 2012
- Cetuximab rechallenge in metastatic colorectal cancer patients: how to come away from acquired resistance?Annals of Oncology, 2012
- Identification of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancerNature Medicine, 2012
- Panitumumab in Patients with KRAS Wild-Type Colorectal Cancer after Progression on CetuximabThe Oncologist, 2012
- Safety and Efficacy of Panitumumab Therapy After Progression With Cetuximab: Experience at Two InstitutionsClinical Colorectal Cancer, 2010
- Analysis of Mutations in DNA Isolated From Plasma and Stool of Colorectal Cancer PatientsGastroenterology, 2008
- EPIC: Phase III Trial of Cetuximab Plus Irinotecan After Fluoropyrimidine and Oxaliplatin Failure in Patients With Metastatic Colorectal CancerJournal of Clinical Oncology, 2008