METIMMOX: Colorectal Cancer METastasis - Shaping Anti-tumor IMMunity by OXaliplatin

Summary

This study aims to determine the efficacy, safety, and tolerability of the sequential addition of immune-modulating therapy to standard-of-care therapy of microsatellite-stable (MSS)/mismatch repair-proficient (pMMR) metastatic colorectal cancer (mCRC).

Timeline

Start

2018-05-29

Primary completion

2024-03-18

Completion

2024-03-18

Outcome

Missed primary endpoint

paper The investigational regimen did not improve the primary outcome for the intention-to-treat population PMID 38664577 ↗

Publications

• Background Dueland S, Ree AH, Groholt KK, Saelen MG, Folkvord S, Hole KH, Seierstad T, Larsen SG, Giercksky KE, Wiig JN, Boye K, Flatmark K. Oxaliplatin-containing Preoperative Therapy in Locally Advanced Rectal Cancer: Local Response, Toxicity and Long-term Outcome. Clin Oncol (R Coll Radiol). 2016 Aug;28(8):532-9. doi: 10.1016/j.clon.2016.01.014. Epub 2016 Feb 14.
• Background Flatmark K, Saelen MG, Hole KH, Abrahamsen TW, Fleten KG, Hektoen HH, Redalen KR, Seierstad T, Dueland S, Ree AH. Individual tumor volume responses to short-course oxaliplatin-containing induction chemotherapy in locally advanced rectal cancer - Targeting the tumor for radiation sensitivity? Radiother Oncol. 2016 Jun;119(3):505-11. doi: 10.1016/j.radonc.2016.02.020. Epub 2016 Mar 8.
• Background Grovik E, Redalen KR, Storas TH, Negard A, Holmedal SH, Ree AH, Meltzer S, Bjornerud A, Gjesdal KI. Dynamic multi-echo DCE- and DSC-MRI in rectal cancer: Low primary tumor Ktrans and DeltaR2* peak are significantly associated with lymph node metastasis. J Magn Reson Imaging. 2017 Jul;46(1):194-206. doi: 10.1002/jmri.25566. Epub 2016 Dec 21.
• Background Joranger P, Nesbakken A, Hoff G, Sorbye H, Oshaug A, Aas E. Modeling and validating the cost and clinical pathway of colorectal cancer. Med Decis Making. 2015 Feb;35(2):255-65. doi: 10.1177/0272989X14544749. Epub 2014 Jul 29.
• Background Kalanxhi E, Hektoen HH, Meltzer S, Dueland S, Flatmark K, Ree AH. Circulating proteins in response to combined-modality therapy in rectal cancer identified by antibody array screening. BMC Cancer. 2016 Jul 26;16:536. doi: 10.1186/s12885-016-2601-x.
• Background Meltzer S, Kalanxhi E, Hektoen HH, Dueland S, Flatmark K, Redalen KR, Ree AH. Systemic release of osteoprotegerin during oxaliplatin-containing induction chemotherapy and favorable systemic outcome of sequential radiotherapy in rectal cancer. Oncotarget. 2016 Jun 7;7(23):34907-17. doi: 10.18632/oncotarget.8995.
• Background Ostrup O, Dagenborg VJ, Rodland EA, Skarpeteig V, Silwal-Pandit L, Grzyb K, Berstad AE, Fretland AA, Maelandsmo GM, Borresen-Dale AL, Ree AH, Edwin B, Nygaard V, Flatmark K. Molecular signatures reflecting microenvironmental metabolism and chemotherapy-induced immunogenic cell death in colorectal liver metastases. Oncotarget. 2017 Jul 18;8(44):76290-76304. doi: 10.18632/oncotarget.19350. eCollection 2017 Sep 29.
• Background Ree AH, Flatmark K, Saelen MG, Folkvord S, Dueland S, Geisler J, Redalen KR. Tumor phosphatidylinositol 3-kinase signaling in therapy resistance and metastatic dissemination of rectal cancer: opportunities for signaling-adapted therapies. Crit Rev Oncol Hematol. 2015 Jul;95(1):114-24. doi: 10.1016/j.critrevonc.2015.01.003. Epub 2015 Jan 12.
• Background Ree AH, Russnes HG, Heinrich D, Dueland S, Boye K, Nygaard V, Silwal-Pandit L, Ostrup O, Hovig E, Nygaard V, Rodland EA, Nakken S, Oien JT, Johansen C, Bergheim IR, Skarpeteig V, Sathermugathevan M, Sauer T, Lund-Iversen M, Beiske K, Nasser S, Julsrud L, Reisse CH, Ruud EA, Florenes VA, Hagene KT, Aas E, Luras H, Johnsen-Soriano S, Geitvik GA, Lingjaerde OC, Borresen-Dale AL, Maelandsmo GM, Flatmark K. Implementing precision cancer medicine in the public health services of Norway: the diagnostic infrastructure and a cost estimate. ESMO Open. 2017 May 2;2(2):e000158. doi: 10.1136/esmoopen-2017-000158. eCollection 2017.
• Background Spindler KG, Boysen AK, Pallisgard N, Johansen JS, Tabernero J, Sorensen MM, Jensen BV, Hansen TF, Sefrioui D, Andersen RF, Brandslund I, Jakobsen A. Cell-Free DNA in Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis. Oncologist. 2017 Sep;22(9):1049-1055. doi: 10.1634/theoncologist.2016-0178. Epub 2017 Aug 4.
• Background Tveit KM, Guren T, Glimelius B, Pfeiffer P, Sorbye H, Pyrhonen S, Sigurdsson F, Kure E, Ikdahl T, Skovlund E, Fokstuen T, Hansen F, Hofsli E, Birkemeyer E, Johnsson A, Starkhammar H, Yilmaz MK, Keldsen N, Erdal AB, Dajani O, Dahl O, Christoffersen T. Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study. J Clin Oncol. 2012 May 20;30(15):1755-62. doi: 10.1200/JCO.2011.38.0915. Epub 2012 Apr 2.
• Ree AH, Hoye E, Esbensen Y, Beitnes AR, Negard A, Bernklev L, Tetlie LK, Fretland AA, Hamre HM, Kersten C, Hofsli E, Guren MG, Sorbye H, Nilsen HL, Flatmark K, Meltzer S. Complete response of metastatic microsatellite-stable BRAF V600E colorectal cancer to first-line oxaliplatin-based chemotherapy and immune checkpoint blockade. Oncoimmunology. 2024 Jun 28;13(1):2372886. doi: 10.1080/2162402X.2024.2372886. eCollection 2024.
• Ree AH, Saltyte Benth J, Hamre HM, Kersten C, Hofsli E, Guren MG, Sorbye H, Johansen C, Negard A, Bjornetro T, Nilsen HL, Berg JP, Flatmark K, Meltzer S. First-line oxaliplatin-based chemotherapy and nivolumab for metastatic microsatellite-stable colorectal cancer-the randomised METIMMOX trial. Br J Cancer. 2024 Jun;130(12):1921-1928. doi: 10.1038/s41416-024-02696-6. Epub 2024 Apr 25.
• Meltzer S, Negard A, Bakke KM, Hamre HM, Kersten C, Hofsli E, Guren MG, Sorbye H, Flatmark K, Ree AH. Early radiologic signal of responsiveness to immune checkpoint blockade in microsatellite-stable/mismatch repair-proficient metastatic colorectal cancer. Br J Cancer. 2022 Dec;127(12):2227-2233. doi: 10.1038/s41416-022-02004-0. Epub 2022 Oct 13.

Drugs

Indications