Colorectal AdenocarcinomaPhase 2METIMMOX-2NCT05504252

METIMMOX-2: Metastatic pMMR/MSS Colorectal Cancer - Shaping Anti-Tumor Immunity by Oxaliplatin

A Phase 2 study testing Nivolumab and Oxaliplatin in people with Colorectal Adenocarcinoma and Mucinous Adenocarcinoma, run by University Hospital, Akershus at 3 sites in Norway.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Hypothesis: Patients with metastatic colorectal cancer with DNA mismatch repair-proficient (pMMR) function / microsatellite-stable (MSS) phenotype harbor a non-immunogenic disease that can be transformed into an immunogenic condition by short-course oxaliplatin-based therapy, and may achieve durable disease control or… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Colorectal Adenocarcinoma, Mucinous Adenocarcinoma, Signet Ring Cell Adenocarcinoma
What is being tested?: Nivolumab and Oxaliplatin
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 80 participants
Where: 3 sitesNorway
Study dates: 5 Oct 2022to 1 Mar 2028
Phase: Phase 2
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patient has histologically verified pMMR/MSS colorectal adenocarcinoma (also comprising the mucinous adenocarcinoma and signet-ring cell carcinoma entities).
Patient is ambulatory with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Patient is at least 18 years of age.
Patient has radiologically measurable metastatic disease.
Patient has an infradiaphragmatic metastatic lesion that can be biopsied.
Patient has not had previous systemic cytotoxic therapy for the metastatic disease, except for previous neoadjuvant treatment.

Show all 19Show fewer

Patient is eligible for the Nordic FLOX regimen when it would be the preferred treatment option for first-line therapy in routine practice.
Patient has the following laboratory values, as measured in serum/plasma within 14 days prior to study entry, indicative of adequate organ function:
Hemoglobin at least 10.0 g/dL
Neutrophils at least 1.5 x10(9)/L (without current use of colony-stimulating factors).
Platelets at least 100 x10(9)/L. - C-reactive protein less than 60 mg/L
AST/ALT no higher than 2xULN when patient does not have metastatic disease in the liver or no higher than 5xULN when patient has metastatic disease in the liver. o Bilirubin no higher than 1.5xULN when patient does not have metastatic disease in the liver or no higher than 2xULN when patient has metastatic disease in the liver
Albumin no lower than 30 g/L. - INR within normal level
Creatinine no higher than 1.5xULN
Woman of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of study drug
WOCBP will use an adequate method to avoid pregnancy for a period of 26 weeks (which includes the required 30 days plus the time required for nivolumab to undergo five half-lives) after the last therapy dose
Woman is not breastfeeding
Male who is sexually active with WOCBP must agree to follow instructions for method(s) of contraception for a period of 26 weeks (which includes the required time to ensure duration of sperm turnover plus the time required for the investigational drugs to undergo five half-lives) after the last therapy dose
Signed informed consent form and expected cooperation of the patients for the treatment and follow-up must be obtained and documented according to International Conference on Harmonization - Good Clinical Practice and national/local regulations

Who cannot join

Patient has metastatic dMMR/MSI colorectal cancer.
Patient has initially resectable metastatic disease for which neoadjuvant therapy is deemed superfluous.
Patient has supradiaphragmatic metastatic disease as the sole site(s).
Patient has untreated or symptomatic brain metastasis (patient must be symptom-free without the use of corticosteroids).
Patient has experienced a period of less than 6 months since discontinuation of neoadjuvant or adjuvant oxaliplatincontaining chemotherapy.
Patient is ineligible for full (100%) chemotherapy doses at first treatment cycle.

Show all 29Show fewer

Patient has partial or complete dihydropyrimidine dehydrogenase (DPD) deficiency.
Patient has had radiation therapy against the only measurable lesion within 4 weeks of start of study treatment.
Patient has a medical condition treated with anticoagulant medication that cannot be replaced by low molecular weight heparin or a direct oral anticoagulant during active study treatment.
Patient has a nervous system disorder worse than CTCAE grade 1.
Patient has any medical condition that will preclude him/her from immune checkpoint blockade therapy, such as:
Active or chronic hepatitis B or hepatitis C. - Known history of human immunodeficiency virus or acquired immunodeficiency-related illnesses.
Diagnosis of immunodeficiency or medical condition requiring systemic steroids or other forms of immunosuppressive therapy.
Autoimmune disease that has required systemic therapy within the past 2 years.
Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving study therapy.
Active infection or chronic infection requiring chronic suppressive antibiotics.
Known history of previous diagnosis of tuberculosis.
Patient with current or prior use of immunosuppressive medication within 28 days before the first dose of study therapy, with the exceptions of intranasal corticosteroids or systemic corticosteroids at physiological doses that do not exceed 10mg/day of prednisone or an equivalent corticosteroid.
Patient has any medical condition or needs to use medication, as listed in the SmPC of each Investigational Medical Product (IMP), that will preclude him/her from receiving treatment with IMP, such as:
Pernicious anemia or anemias due to vitamin B12 deficiency (SmPC-listed contraindications for folinic acid).
A known complete absence of DPD activity.
Has been treated with brivudine, sorivudine, or their chemically related analogs, which are potent inhibitors of the enzyme DPD that degrades fluorouracil. Fluorouracil must not be taken within 4 weeks of treatment with brivudine, sorivudine, or their chemically related analogs.
Other SmPC-listed contraindications for the IMPs are covered by other exclusion criteria.
Patient has undergone treatment with any IMP that may interfere with the study treatment within 4 weeks prior to first administration of study drug.
Patient has known hypersensitivity to any of the study IMP components.
Patient has history of other prior malignancy, with the exception of curatively treated basal cell or squamous cell carcinoma of the skin, cervical cancer stage IB, stage I prostate cancer considered not necessary to treat, and another malignancy that was treated with curative intent more than 5 years ago and has not relapsed later.
Patient has significant cardiac, pulmonary, or other medical illness that would limit activity of daily life or survival.
Patient is pregnant or breastfeeding.
Patient has any other reason, in the opinion of Clinical Investigator, not to participate in the study.

Trial locations and contacts

3 sites in 1 country.

Norway3 sites

Akershus University Hospital
Lørenskog, Akershus, 1478
Oslo University Hospital
Oslo, Akershus, 0424
St Olavs Hospital
Trondheim, Trøndelag, 7006

Other trials in Norway

About this study

Read the detailed description

The study has a start-up single-arm design consisting of 2 cycles of the Nordic FLOX regimen followed by 2 cycles of nivolumab for a total of 4 individual cycles (8 weeks, or longer if cycles have been delayed) before radiologic response assessment and patient stratification to continued therapy.

Patients who present less than 10% target lesion reduction at the first radiologic response assessment will proceed to standard-of-care treatment at the Clinical Investigator's discretion. Patients will be followed for PFS (from the date of study enrolment).

Patients who present 10% or higher target lesion reduction at the first radiologic response assessment will continue treatment with alternating 2 cycles of the Nordic FLOX regimen and 2 cycles of nivolumab. From the time of stratification, radiologic response assessment will be every 8 weeks. After a total of 12 individual cycles (4 initial cycles followed by 8 continuation cycles; Sequence 1), patients will enter a break that will persist until disease progression, following radiologic assessment every 8 weeks during the break, when therapy is reintroduced and administered for another total of 12 individual cycles (Sequence 2) before a new break. This go-and-stop schedule will be continued until progressive disease on ongoing therapy (defining PFS), intolerable toxicity, withdrawal of consent, or death, whichever occurs first.

Conditions: Colorectal Adenocarcinoma, Mucinous Adenocarcinoma, Signet Ring Cell Adenocarcinoma
Being tested: Nivolumab, Oxaliplatin
Keywords: Immune checkpoint inhibitor (nivolumab), Oxaliplatin
Medical subject headings: Adenocarcinoma, Mucinous, Carcinoma, Signet Ring Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NivolumabDrug
Also called Opdivo
Q2W
Nivolumab: 240 mg fixed dose over 30 minutes, IV administration every 2 weeks
OxaliplatinDrug
Also called 5-fluorouracil, folinic acid
FLOX, Q2W

Study groups in NCT05504252
Study group	Role	What they receive
Experimental Arm	Experimental	The study has a start-up single-arm design consisting of 2 cycles of the Nordic FLOX regimen followed by 2 cycles of nivolumab for a total of 4 individual cycles before radiologic response assessment and patient stratification to continued therapy or not. Patients who present less than 10% target lesion reduction at the first radiologic response assessment will proceed to standard-of-care treatment at the Clinical Investigator's discretion. Patients who present 10% or higher target lesion reduction at the first radiologic response assessment will continue with alternating 2 cycles of the Nordic FLOX regimen and 2 cycles of nivolumab in a go-and-stop schedule until progressive disease on ongoing therapy (defining PFS), intolerable toxicity, withdrawal of consent, or death, whichever occurs first. Receives: Drug: Nivolumab; Drug: Oxaliplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

Progression-free survival
To determine PFS, in terms of continuation of treatment strategy, of repeat sequential treatment with the Nordic FLOX regimen and nivolumab in patients with previously untreated unresectable metastatic pMMR/MSS colorectal cancer reaching 10% or higher target lesion reduction at the first radiologic restaging.
Measured: From date of the first FLOX cycle until the date of disease progression on ongoing therapy or death, whichever occurs first, assessed up to 60 months

Secondary outcomes (6)

Incidence of adverse events
Safety
Measured: From date of the first FLOX cycle until 100 days following discontinuation of the study treatment, assessed up to 60 months
Grading of adverse events
Tolerability
Measured: From date of the first FLOX cycle until 100 days following discontinuation of the study treatment, assessed up to 60 months
Objective response rate
ORR
Measured: Through study completion, an average of 18 months
Duration of response
DoR
Measured: From date of the best overall response until the date of disease progression, assessed up to 60 months
Secondary surgical curative-intent resection rate
SSCiR
Measured: Through study completion, an average of 18 months
Overall survival
OS
Measured: From date of the first FLOX cycle until the date of death, assessed up to 60 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Oct 20221 Mar 2028

First posted17 Aug 2022
Study start5 Oct 2022
Primary completion31 Jan 2028 (estimated)
Study completion1 Mar 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (29)Papers the sponsor has linked to this study.
Other trials for Colorectal AdenocarcinomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 80 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05504252
Sponsor's protocol ID: 2022-500027-76-00
Other IDs: 2022-500027-76-00
Acronym: METIMMOX-2
Status last verified: Jan 2026
First submitted: 12 Aug 2022
Last updated: 7 Jan 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: The listed study information can be made available from the Principal Investigator on reasonable request and in accordance with the General Data Protection Regulation of the European Union.

Publications

Abrahamsson H, Jensen BV, Berven LL, Nielsen DL, Saltyte Benth J, Johansen JS, Larsen FO, Johansen JS, Ree AH. Antitumour immunity invoked by hepatic arterial infusion of first-line oxaliplatin predicts durable colorectal cancer control after liver metastasis ablation: 8-12 years of follow-up. Int J Cancer. 2020 Apr 1;146(7):2019-2026. doi: 10.1002/ijc.32847. Epub 2020 Jan 7.
PubMed 31872440
Andre T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020 Dec 3;383(23):2207-2218. doi: 10.1056/NEJMoa2017699.
PubMed 33264544
Bains SJ, Abrahamsson H, Flatmark K, Dueland S, Hole KH, Seierstad T, Redalen KR, Meltzer S, Ree AH. Immunogenic cell death by neoadjuvant oxaliplatin and radiation protects against metastatic failure in high-risk rectal cancer. Cancer Immunol Immunother. 2020 Mar;69(3):355-364. doi: 10.1007/s00262-019-02458-x. Epub 2019 Dec 31.
PubMed 31893287
Borcoman E, Kanjanapan Y, Champiat S, Kato S, Servois V, Kurzrock R, Goel S, Bedard P, Le Tourneau C. Novel patterns of response under immunotherapy. Ann Oncol. 2019 Mar 1;30(3):385-396. doi: 10.1093/annonc/mdz003.
PubMed 30657859
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.
PubMed 30207593
Dagenborg VJ, Marshall SE, Yaqub S, Grzyb K, Boye K, Lund-Iversen M, Hoye E, Berstad AE, Fretland AA, Edwin B, Ree AH, Flatmark K. Neoadjuvant chemotherapy is associated with a transient increase of intratumoral T-cell density in microsatellite stable colorectal liver metastases. Cancer Biol Ther. 2020 May 3;21(5):432-440. doi: 10.1080/15384047.2020.1721252. Epub 2020 Feb 26.
PubMed 32098573
Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745.
PubMed 32402160
Galluzzi L, Vitale I, Warren S, Adjemian S, Agostinis P, Martinez AB, Chan TA, Coukos G, Demaria S, Deutsch E, Draganov D, Edelson RL, Formenti SC, Fucikova J, Gabriele L, Gaipl US, Gameiro SR, Garg AD, Golden E, Han J, Harrington KJ, Hemminki A, Hodge JW, Hossain DMS, Illidge T, Karin M, Kaufman HL, Kepp O, Kroemer G, Lasarte JJ, Loi S, Lotze MT, Manic G, Merghoub T, Melcher AA, Mossman KL, Prosper F, Rekdal O, Rescigno M, Riganti C, Sistigu A, Smyth MJ, Spisek R, Stagg J, Strauss BE, Tang D, Tatsuno K, van Gool SW, Vandenabeele P, Yamazaki T, Zamarin D, Zitvogel L, Cesano A, Marincola FM. Consensus guidelines for the definition, detection and interpretation of immunogenic cell death. J Immunother Cancer. 2020 Mar;8(1):e000337. doi: 10.1136/jitc-2019-000337.
PubMed 32209603
Grasso CS, Giannakis M, Wells DK, Hamada T, Mu XJ, Quist M, Nowak JA, Nishihara R, Qian ZR, Inamura K, Morikawa T, Nosho K, Abril-Rodriguez G, Connolly C, Escuin-Ordinas H, Geybels MS, Grady WM, Hsu L, Hu-Lieskovan S, Huyghe JR, Kim YJ, Krystofinski P, Leiserson MDM, Montoya DJ, Nadel BB, Pellegrini M, Pritchard CC, Puig-Saus C, Quist EH, Raphael BJ, Salipante SJ, Shin DS, Shinbrot E, Shirts B, Shukla S, Stanford JL, Sun W, Tsoi J, Upfill-Brown A, Wheeler DA, Wu CJ, Yu M, Zaidi SH, Zaretsky JM, Gabriel SB, Lander ES, Garraway LA, Hudson TJ, Fuchs CS, Ribas A, Ogino S, Peters U. Genetic Mechanisms of Immune Evasion in Colorectal Cancer. Cancer Discov. 2018 Jun;8(6):730-749. doi: 10.1158/2159-8290.CD-17-1327. Epub 2018 Mar 6.
PubMed 29510987
Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, Bot BM, Morris JS, Simon IM, Gerster S, Fessler E, De Sousa E Melo F, Missiaglia E, Ramay H, Barras D, Homicsko K, Maru D, Manyam GC, Broom B, Boige V, Perez-Villamil B, Laderas T, Salazar R, Gray JW, Hanahan D, Tabernero J, Bernards R, Friend SH, Laurent-Puig P, Medema JP, Sadanandam A, Wessels L, Delorenzi M, Kopetz S, Vermeulen L, Tejpar S. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015 Nov;21(11):1350-6. doi: 10.1038/nm.3967. Epub 2015 Oct 12.
PubMed 26457759
Hadden WJ, de Reuver PR, Brown K, Mittal A, Samra JS, Hugh TJ. Resection of colorectal liver metastases and extra-hepatic disease: a systematic review and proportional meta-analysis of survival outcomes. HPB (Oxford). 2016 Mar;18(3):209-20. doi: 10.1016/j.hpb.2015.12.004. Epub 2016 Feb 1.
PubMed 27017160
Hoos A, Wolchok JD, Humphrey RW, Hodi FS. CCR 20th Anniversary Commentary: Immune-Related Response Criteria--Capturing Clinical Activity in Immuno-Oncology. Clin Cancer Res. 2015 Nov 15;21(22):4989-91. doi: 10.1158/1078-0432.CCR-14-3128.
PubMed 26567357
Kalanxhi E, Meltzer S, Schou JV, Larsen FO, Dueland S, Flatmark K, Jensen BV, Hole KH, Seierstad T, Redalen KR, Nielsen DL, Ree AH. Systemic immune response induced by oxaliplatin-based neoadjuvant therapy favours survival without metastatic progression in high-risk rectal cancer. Br J Cancer. 2018 May;118(10):1322-1328. doi: 10.1038/s41416-018-0085-y. Epub 2018 Apr 26.
PubMed 29695770
Lee JW, Stone ML, Porrett PM, Thomas SK, Komar CA, Li JH, Delman D, Graham K, Gladney WL, Hua X, Black TA, Chien AL, Majmundar KS, Thompson JC, Yee SS, O'Hara MH, Aggarwal C, Xin D, Shaked A, Gao M, Liu D, Borad MJ, Ramanathan RK, Carpenter EL, Ji A, de Beer MC, de Beer FC, Webb NR, Beatty GL. Hepatocytes direct the formation of a pro-metastatic niche in the liver. Nature. 2019 Mar;567(7747):249-252. doi: 10.1038/s41586-019-1004-y. Epub 2019 Mar 6.
PubMed 30842658
Lenz HJ, Van Cutsem E, Luisa Limon M, Wong KYM, Hendlisz A, Aglietta M, Garcia-Alfonso P, Neyns B, Luppi G, Cardin DB, Dragovich T, Shah U, Abdullaev S, Gricar J, Ledeine JM, Overman MJ, Lonardi S. First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study. J Clin Oncol. 2022 Jan 10;40(2):161-170. doi: 10.1200/JCO.21.01015. Epub 2021 Oct 12.
PubMed 34637336

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 7 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: METIMMOX-2: Metastatic pMMR/MSS Colorectal Cancer - Shaping Anti-Tumor Immunity by Oxaliplatin
ClinicalTrials.gov ID: NCT05504252
Acronym / sponsor ID: METIMMOX-2 / 2022-500027-76-00
Conditions: Colorectal Adenocarcinoma, Mucinous Adenocarcinoma, Signet Ring Cell Adenocarcinoma
Keywords: Immune checkpoint inhibitor (nivolumab), Oxaliplatin
Phase: Phase 2
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 80 participants (estimated)
Lead sponsor: University Hospital, AkershusUniversity, hospital or other
Collaborators: Oslo University Hospital, St. Olavs Hospital
Study start: 5 Oct 2022 (actual)
Primary completion: 31 Jan 2028 (estimated)
Study completion: 1 Mar 2028 (estimated)
First posted: 17 Aug 2022 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Experimental Arm	Experimental	Drug: Nivolumab, Drug: OxaliplatinThe study has a start-up single-arm design consisting of 2 cycles of the Nordic FLOX regimen followed by 2 cycles of nivolumab for a total of 4 individual cycles before radiologic response assessment and patient stratification to continued therapy or not. Patients who present less than 10% target lesion reduction at the first radiologic response assessment will proceed to standard-of-care treatment at the Clinical Investigator's discretion. Patients who present 10% or higher target lesion reduction at the first radiologic response assessment will continue with alternating 2 cycles of the Nordic FLOX regimen and 2 cycles of nivolumab in a go-and-stop schedule until progressive disease on ongoing therapy (defining PFS), intolerable toxicity, withdrawal of consent, or death, whichever occurs first.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (19 listed)

Patient has histologically verified pMMR/MSS colorectal adenocarcinoma (also comprising the mucinous adenocarcinoma and signet-ring cell carcinoma entities).
Patient is ambulatory with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Patient is at least 18 years of age.
Patient has radiologically measurable metastatic disease.
Patient has an infradiaphragmatic metastatic lesion that can be biopsied.

Key exclusion criteria (29 listed)

Patient has metastatic dMMR/MSI colorectal cancer.
Patient has initially resectable metastatic disease for which neoadjuvant therapy is deemed superfluous.
Patient has supradiaphragmatic metastatic disease as the sole site(s).
Patient has untreated or symptomatic brain metastasis (patient must be symptom-free without the use of corticosteroids).
Patient has experienced a period of less than 6 months since discontinuation of neoadjuvant or adjuvant oxaliplatincontaining chemotherapy.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NivolumabAlso: OpdivoQ2W Nivolumab: 240 mg fixed dose over 30 minutes, IV administration every 2 weeks	Drug	Experimental Arm
OxaliplatinAlso: 5-fluorouracil, folinic acidFLOX, Q2W	Drug	Experimental Arm

Primary outcome

Progression-free survival
Time frame: From date of the first FLOX cycle until the date of disease progression on ongoing therapy or death, whichever occurs first, assessed up to 60 months
To determine PFS, in terms of continuation of treatment strategy, of repeat sequential treatment with the Nordic FLOX regimen and nivolumab in patients with previously untreated unresectable metastatic pMMR/MSS colorectal cancer reaching 10% or higher target lesion reduction at the first radiologic restaging.

6 secondary outcomes

Incidence of adverse events
Time frame: From date of the first FLOX cycle until 100 days following discontinuation of the study treatment, assessed up to 60 months
Grading of adverse events
Time frame: From date of the first FLOX cycle until 100 days following discontinuation of the study treatment, assessed up to 60 months
Objective response rate
Time frame: Through study completion, an average of 18 months
Duration of response
Time frame: From date of the best overall response until the date of disease progression, assessed up to 60 months
Secondary surgical curative-intent resection rate
Time frame: Through study completion, an average of 18 months
Overall survival
Time frame: From date of the first FLOX cycle until the date of death, assessed up to 60 months

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2026.
Background: PubMed 31872440Abrahamsson H, Jensen BV, Berven LL, Nielsen DL, Saltyte Benth J, Johansen JS, Larsen FO, Johansen JS, Ree AH. Antitumour immunity invoked by hepatic arterial infusion of first-line oxaliplatin predicts durable colorectal cancer control after liver metastasis ablation: 8-12 years of follow-up. Int J Cancer. 2020 Apr 1;146(7):2019-2026. doi: 10.1002/ijc.32847. Epub 2020 Jan 7.
Background: PubMed 33264544Andre T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz LA Jr; KEYNOTE-177 Investigators. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. N Engl J Med. 2020 Dec 3;383(23):2207-2218. doi: 10.1056/NEJMoa2017699.
Background: PubMed 31893287Bains SJ, Abrahamsson H, Flatmark K, Dueland S, Hole KH, Seierstad T, Redalen KR, Meltzer S, Ree AH. Immunogenic cell death by neoadjuvant oxaliplatin and radiation protects against metastatic failure in high-risk rectal cancer. Cancer Immunol Immunother. 2020 Mar;69(3):355-364. doi: 10.1007/s00262-019-02458-x. Epub 2019 Dec 31.
Background: PubMed 30657859Borcoman E, Kanjanapan Y, Champiat S, Kato S, Servois V, Kurzrock R, Goel S, Bedard P, Le Tourneau C. Novel patterns of response under immunotherapy. Ann Oncol. 2019 Mar 1;30(3):385-396. doi: 10.1093/annonc/mdz003.
Background: PubMed 30207593Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.
Background: PubMed 32098573Dagenborg VJ, Marshall SE, Yaqub S, Grzyb K, Boye K, Lund-Iversen M, Hoye E, Berstad AE, Fretland AA, Edwin B, Ree AH, Flatmark K. Neoadjuvant chemotherapy is associated with a transient increase of intratumoral T-cell density in microsatellite stable colorectal liver metastases. Cancer Biol Ther. 2020 May 3;21(5):432-440. doi: 10.1080/15384047.2020.1721252. Epub 2020 Feb 26.
Background: PubMed 32402160Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745.
Background: PubMed 32209603Galluzzi L, Vitale I, Warren S, Adjemian S, Agostinis P, Martinez AB, Chan TA, Coukos G, Demaria S, Deutsch E, Draganov D, Edelson RL, Formenti SC, Fucikova J, Gabriele L, Gaipl US, Gameiro SR, Garg AD, Golden E, Han J, Harrington KJ, Hemminki A, Hodge JW, Hossain DMS, Illidge T, Karin M, Kaufman HL, Kepp O, Kroemer G, Lasarte JJ, Loi S, Lotze MT, Manic G, Merghoub T, Melcher AA, Mossman KL, Prosper F, Rekdal O, Rescigno M, Riganti C, Sistigu A, Smyth MJ, Spisek R, Stagg J, Strauss BE, Tang D, Tatsuno K, van Gool SW, Vandenabeele P, Yamazaki T, Zamarin D, Zitvogel L, Cesano A, Marincola FM. Consensus guidelines for the definition, detection and interpretation of immunogenic cell death. J Immunother Cancer. 2020 Mar;8(1):e000337. doi: 10.1136/jitc-2019-000337.
Background: PubMed 29510987Grasso CS, Giannakis M, Wells DK, Hamada T, Mu XJ, Quist M, Nowak JA, Nishihara R, Qian ZR, Inamura K, Morikawa T, Nosho K, Abril-Rodriguez G, Connolly C, Escuin-Ordinas H, Geybels MS, Grady WM, Hsu L, Hu-Lieskovan S, Huyghe JR, Kim YJ, Krystofinski P, Leiserson MDM, Montoya DJ, Nadel BB, Pellegrini M, Pritchard CC, Puig-Saus C, Quist EH, Raphael BJ, Salipante SJ, Shin DS, Shinbrot E, Shirts B, Shukla S, Stanford JL, Sun W, Tsoi J, Upfill-Brown A, Wheeler DA, Wu CJ, Yu M, Zaidi SH, Zaretsky JM, Gabriel SB, Lander ES, Garraway LA, Hudson TJ, Fuchs CS, Ribas A, Ogino S, Peters U. Genetic Mechanisms of Immune Evasion in Colorectal Cancer. Cancer Discov. 2018 Jun;8(6):730-749. doi: 10.1158/2159-8290.CD-17-1327. Epub 2018 Mar 6.
Background: PubMed 26457759Guinney J, Dienstmann R, Wang X, de Reynies A, Schlicker A, Soneson C, Marisa L, Roepman P, Nyamundanda G, Angelino P, Bot BM, Morris JS, Simon IM, Gerster S, Fessler E, De Sousa E Melo F, Missiaglia E, Ramay H, Barras D, Homicsko K, Maru D, Manyam GC, Broom B, Boige V, Perez-Villamil B, Laderas T, Salazar R, Gray JW, Hanahan D, Tabernero J, Bernards R, Friend SH, Laurent-Puig P, Medema JP, Sadanandam A, Wessels L, Delorenzi M, Kopetz S, Vermeulen L, Tejpar S. The consensus molecular subtypes of colorectal cancer. Nat Med. 2015 Nov;21(11):1350-6. doi: 10.1038/nm.3967. Epub 2015 Oct 12.
Background: PubMed 27017160Hadden WJ, de Reuver PR, Brown K, Mittal A, Samra JS, Hugh TJ. Resection of colorectal liver metastases and extra-hepatic disease: a systematic review and proportional meta-analysis of survival outcomes. HPB (Oxford). 2016 Mar;18(3):209-20. doi: 10.1016/j.hpb.2015.12.004. Epub 2016 Feb 1.
Background: PubMed 26567357Hoos A, Wolchok JD, Humphrey RW, Hodi FS. CCR 20th Anniversary Commentary: Immune-Related Response Criteria--Capturing Clinical Activity in Immuno-Oncology. Clin Cancer Res. 2015 Nov 15;21(22):4989-91. doi: 10.1158/1078-0432.CCR-14-3128.
Individual participant dataSharing planned: Yes. The listed study information can be made available from the Principal Investigator on reasonable request and in accordance with the General Data Protection Regulation of the European Union.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Christian Kersten, MD, PhD study chair

University Hospital, Akershus

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab and Oxaliplatin in people with Colorectal Adenocarcinoma and Mucinous Adenocarcinoma, run by University Hospital, Akershus at 3 sites in Norway.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 7 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (time frame: From date of the first FLOX cycle until the date of disease progression on ongoing therapy or death, whichever occurs first, assessed up to 60 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05504252, which also lists 29 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2026.