ICECREAM: The Irinotecan Cetuximab Evaluation and the Cetuximab Response Evaluation Among Patients with G13D Mutation. A randomised Phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic CRC with either <em>KRAS</em> WT or G13D mutation.

ICECREAM: The Irinotecan Cetuximab Evaluation and the Cetuximab Response Evaluation Among Patients with G13D Mutation. A randomised Phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic CRC with either KRAS WT or G13D mutation.

ICECREAM: The Irinotecan Cetuximab Evaluation and the Cetuximab Response Evaluation Among Patients with G13D Mutation. A randomised Phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic CRC with either KRAS WT or G13D mutation. (10544)

Eva Segelov ¹

St Vincent's Hospital, Darlinghurst, NSW, Australia

AIMS - This study aims to provide important data on the optimal use of currently available therapeutics in patients with metastatic CRC who have progressed on standard chemotherapy options. The trial is designed to study two questions in parallel.

This first is to determine whether cetuximab is optimally used as monotherapy or in combination with an irinotecan-based regimen in KRAS WT patients, and the second is to determine whether the efficacy of either cetuximab alone or in combination with an irinotecan-based regimen is similar in patients harbouring a KRAS G13D mutation, as has been suggested by retrospective analysis of several clinical trials.

The results will impact the standard treatment for both groups of patients and may influence the policy on cetuximab administration, including allowing KRAS G13D mutated colorectal cancer patients to have access to treatment that is currently unavailable in Australia.

BACKGROUND - Patients with metastatic colorectal cancer who have progressed on oxaliplatin and irinotecan containing regimens may benefit from the use of EGFR-inhibiting monoclonal antibodies such as cetuximab, if they contain no mutations in their KRAS gene (ie are wild type- WT). However, it is unknown whether in this setting these antibodies, such as cetuximab being used in this study, are more efficacious used as monotherapy or in combination with irinotecan, as suggested by the BOND study which did not select for KRAS status.

This study will also provide prospective data on the activity of the EGFR monoclonal antibodies in the subgroup of patients with a specific KRAS mutation in codon G13D. Patients with this specific mutation appear in retrospective analyses to derive similar benefit as WT patients, but currently have no access to the therapy. Therefore this study aims to provide important data on the optimal use of currently available therapeutics in patients with metastatic CRC who have progressed on standard chemotherapy options.

STUDY DESIGN - This is a phase II, open label, randomised multi-centre trial. Patients with histologically confirmed CRC with either “quadruple WT" genotype (no mutations also in BRAF, NRAS, PIK3CA exon20) or KRAS G13D mutation will be randomised to receive either cetuximab monotherapy or the combination of cetuximab and irinotecan chemotherapy and will be stratified according to KRAS mutational status (WT vs G13D). A total of 100 patients will be randomised to the study, 50 KRAS WT patients (25 receiving cetuximab monotherapy and 25 receiving cetuximab and irinotecan chemotherapy) and 50 KRAS G13D patients (25 receiving cetuximab monotherapy and 25 receiving cetuximab and irinotecan chemotherapy). Patients will continue their assigned treatment

until disease progression, unless there is unacceptable toxicity or either the patient or physician requests cessation of treatment.

The primary objective is 6 month progression free survival. Secondary objectives are response rate, overall survival, quality of life, and translational research including markers that may predict response such as amphiregulin and epiregulin determined by immunohistochemistry.

TRANSLATIONAL RESEARCH - Patients are asked to consent for blood and tissue collection for future translational research. The blood samples are collected at baseline, six weeks, and then at disease progression. Tissue and blood samples will be stored centrally at the Centre for Translational Pathology in Melbourne.

STUDY PROGRESS - The study opened to recruitment in November 2012, and will be conducted at 15 sites, 12 of which are in Australia, and one site each in the UK, Italy and Spain. At early September 2013 25 patients (8 WT: 17 G13D) have been randomised. ICECREAM was selected for poster display within the Trials in Progress session at ASCO 2013 where an international investigator dinner meeting was held as well. An abstract for an ICECREAM poster in the Trials in Progress session at COSA has been accepted. An Investigator Dinner will be held as part of the 2013 AGITG ASM.

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Authors contributing to this presentation.

Segelov, E

Professor Eva Segelov was appointed as the Professor and Director of Oncology at Monash Health and Monash University in February 2017. She is an Honorary Associate of the NHMRC Clinical Trials Centre, Sydney Medical School and previously Associate Professor at the University of New South Wales and Senior Medical Oncologist at St Vincent’s Hospital, Sydney. She is a recognised national and international expert in the fields of gastrointestinal cancer, including neuroendocrine tumours, and breast cancer, with a 20-year history of management of patients in a multidisciplinary setting. Professor Segelov is an active member of the Australian Gastrointestinal Trials Group (AGITG), as a Board Member and Convenor of the Annual Scientific Meeting. She is Chair of the Gastrointestinal Group of the Clinical Oncological Society of Australia (COSA). In 2016 she was nominated as a European Society of Medical Oncology (ESMO) faculty member for the CUP, Endocrine Tumours, and Others group. She is an Associate Editor of Journal of Global Oncology (ASCO); Editorial Board member of JoVE Cancer Research; ESMO 2019 Scientific Sub-Committee member for Neuroendocrine cancer; co-Track Chair of Gastrointestinal Cancer for the 2017 ESMO Asia Annual Scientific Meeting and co-founder of the Commonwealth Neuroendocrine Tumour Society (CommNETS), an international research collaborative. Professor Segelov has led multiple national and international oncology clinical trials, including investigator-initiated studies. Her research interests relate to translational studies of targeted therapies in defined subpopulations to increase benefit and reduce the toxicity of cancer treatments. She has published over 80 articles, expert reviews, and book chapters and is a frequent invited speaker at national and international conferences. Professor Segelov has a particular interest in professional development using innovative learning techniques and has developed the Seminal Advances Preceptorship in Cancer courses, now being run through Monash University. She was awarded the UNSW Vice Chancellors Award for Teaching Excellence in 2006.

ICECREAM: The Irinotecan Cetuximab Evaluation and the Cetuximab Response Evaluation Among Patients with G13D Mutation. A randomised Phase II study of cetuximab alone or in combination with irinotecan in patients with metastatic CRC with either KRAS WT or G13D mutation. (10544)

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