Abstract
Immunotherapy with Y90-radioembolization for metastatic colorectal cancer (iRE-C)
Journal of clinical oncology, Vol.38(4_suppl), pp.TPS276-TPS276
02/01/2020
DOI: 10.1200/JCO.2020.38.4_suppl.TPS276
Abstract
TPS276
Background: Immune checkpoint inhibitors have revolutionized the treatment of a number of cancers. In colorectal cancers, their efficacy is limited to mismatch repair deficient or microsatellite stability-high (dMMR/MSI-High) tumors only. These constitute only 4-5% of all metastatic colorectal cancers (mCRC). Novel approaches are needed to make immunotherapy a viable option for mismatch repair proficient or microsatellite stable (pMMR/MSS) tumors. Increasing exposure of neo-antigens to the immune system could be one potential strategy to enhance the response of immunotherapy. Yttrium 90-radioembolization (Y90-RE) in combination with immunotherapy may work synergistically to enhance efficacy of each other. Additionally, radiation can potentially make the tumor microenvironment conducive to effector T-cell recruitment and function. Therefore, we hypothesize and propose the clinical trial of combining immunotherapy with Y90-RE as a feasible and safe strategy that will improve outcomes in patients with mCRC with liver-predominant metastases. Methods: This clinical trial will be conducted as a single-center, open-label, Phase I/II trial to evaluate initially the feasibility and safety of Y90-RE in combination with a fixed dose of immunotherapy (durvalumab) in subjects with liver-predominant, mCRC (Table). It will be offered in the refractory setting. The trial will be performed in 18 subjects with mCRC with liver metastasis and the safety of immunotherapy (durvalumab) with Y90-RE will be investigated in an accelerated titration design. This would allow a maximum tolerated dose with the minimum number of subjects. Correlative studies pertaining to serial circulating tumor DNA (ctDNA - liquid biopsies) testing as well as immune-panel based profiling will be performed alongside pre- and post-biopsies to study changes in the tumor microenvironment. Clinical trial information: NCT04108481.
[Table: see text]
Details
- Title: Subtitle
- Immunotherapy with Y90-radioembolization for metastatic colorectal cancer (iRE-C)
- Creators
- Pashtoon Murtaza Kasi - University of IowaBeau M Toskich - Mayo Clinic in FloridaChandrikha Chandrasekharan - University of IowaDhivya Prabhakar - University of IowaSaima Sharif - University of IowaDaniel James Berg - University of IowaAnn Miller - University of IowaCarlos Hou Fai Chan - Brigham and Women's HospitalSandeep Laroia - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Journal of clinical oncology, Vol.38(4_suppl), pp.TPS276-TPS276
- DOI
- 10.1200/JCO.2020.38.4_suppl.TPS276
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Grant note
- name: Biocompatibles UK Ltd and AstraZeneca
- Language
- English
- Date published
- 02/01/2020
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine; Microbiology and Immunology; Radiology; Surgery; Radiation Oncology
- Record Identifier
- 9984320088902771
Metrics
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