Colorectal CancerPhase 2ANICCANCT03981146
A Phase II Trial Assessing Nivolumab in Class II Expressing Microsatellite Stable Colorectal Cancer
A Phase 2 study testing Nivolumab in people with Colorectal Cancer, run by University of Birmingham at 14 sites in United Kingdom.
Trial summary
An open-label, single-arm, phase II, multicentre clinical trial to determine the rate of durable clinical benefit of nivolumab in patients with class II expressing microsatellite stable colorectal cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 14 sitesUnited Kingdom
- Study dates
- 28 Aug 2019to 26 Nov 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Histologically confirmed locally advanced or metastatic MSS CRC with class II expression (greater than 1% cancer cell positivity for class II expression on immunohistochemistry).
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (APPENDIX 1)
- Age ≥ 18 years
- Patients must have completed all standard of care therapy that the treating oncologist deems appropriate. Trial treatment as first line therapy is permitted if the patient has declined standard of care therapy.
- CT scan of chest, abdomen, pelvis within 28 days of registration demonstrating unidimensionally measurable disease as per RECIST version 1.1 (APPENDIX 3).
- Demonstrate adequate haematological function:
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- Platelet count ≥100 x 109 /L
- Neutrophils ≥1.5 x 109/L
- Haemoglobin ≥ 90 g/L
- Demonstrate adequate hepatic function:
- Serum bilirubin ≤1.5 x upper limit of normal (ULN)
- Serum AST or ALT ≤2.5 x ULN or <5 x ULN in the presence of liver metastases
- Demonstrate adequate renal function
- o Creatinine clearance <1.5 times ULN and >30ml/min (as per institutional standard).
- Provision of signed and dated, written informed consent prior to any trial specific procedures, sampling and analyses.
- Negative pregnancy test (female patients of reproductive potential). (Serum Test must be negative)
- Patients must agree to the use of contraception as detailed in section 7.8
Who cannot join
- Previous treatment with PD1/PDL1 inhibitors.
- Untreated symptomatic brain or leptomeningeal metastatic disease.
- Medical or psychiatric conditions compromising informed consent.
- Any medical condition which, in the opinion of the Investigator, would compromise the ability of the patient to participate in the trial or which would jeopardise compliance with the protocol.
- Administration of chemotherapy, radioactive or biological cancer therapy within 4 weeks prior to the first dose of trial therapy Patient has not recovered to CTCAE grade 1 or better from the Adverse Event (AE) due to cancer therapeutics administered more than 4 weeks earlier.
- Active autoimmune disease that has required systemic treatment in past 2 years (i.e.
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- with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
- Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patient has risk factors for bowel obstruction or bowel perforation (examples include but not limited to a history of acute diverticulitis, intra-abdominal abscess and abdominal carcinomatosis).
- Patient has a known history of other malignancy, unless the patient has undergone potentially curative therapy with no evidence of that disease for 3 years.
- Has a history of non-infectious pneumonitis requiring steroids or has active pneumonitis.
- Female patients that are either pregnant or breast feeding.
- Male and female patients (of childbearing age) not willing to use adequate contraception.
- Patient previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody.
- Patient is positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA (qualitative) is detected); patients with negative Hepatitis C antibody testing may not need RNA testing.
- Known history of tuberculosis.
- Patient has an active infection requiring therapy.
- Has received a live vaccine within 30 days prior to the first dose of trial treatment.
- Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United Kingdom14 sites
Belfast City Hospital
Belfast
Queen Elizabeth Hospital
Birmingham
Velindre Cancer Centre
Cardiff
Western General Hospital
Edinburgh
St James Leeds
Leeds, LS9 7TF
Leicester Royal Infirmary
Leicester, LE1 5WW
Clatterbridge Cancer Centre
Liverpool
The Royal Free Hospital
London, NW3 2QG
Guys Hospital
London
The Royal Marsden NHS Foundation Trust
London
University College Hospital
London
The Christie Hospital, The Christie NHS Foundation Trust
Manchester
Freemans Hospital
Newcastle upon Tyne
Weston Park
Sheffield, S10 2SJ
About this study
An open-label, single-arm, phase II, multicentre clinical trial to determine the rate of durable clinical benefit of nivolumab in patients with class II expressing microsatellite stable colorectal cancer.
Read the detailed description
Immuno-oncology is transforming the care of certain patients with cancer. Not all patients respond to these therapies however, and in some common cancers checkpoint blockade has failed to make any real impact. In 2014 there were over 41,000 new cases of colorectal cancer (CRC) in the UK and nearly 16,000 deaths from the disease, making it the second commonest cause of cancer death (Cancer Research UK Cancer Statistics Key Facts). 15% of patients with CRC develop it as a result of deficient mismatch repair (microsatellite instability - MSI): this cohort of patients respond well to PD-1/PD-L1 blockade as these tumours harbour a very high number of mutations thus increasing the likelihood of the presence of immunogenic neo-epitopes which elicit an immune response1. The majority of CRC patients, particularly those with metastatic disease (around 95%), do not display this hyper-mutator phenotype (microsatellite stable (MSS) CRC) and in these patients the results of PD-1/PD-L1 blockade have been disappointing.
In summary, MSS CRC patients with a class II expression appear to represent immunologically a group of MSI-like MSS patients that may respond to usefully to the immunotherapy agent nivolumab as a single agent and thus a trial of nivolumab in patients with class II expression of their cancer cells appears to be highly justified.
- Conditions
- Colorectal Cancer
- Being tested
- Nivolumab
- Keywords
- Class II Microsatellite Status
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo
60 Minute IV Infusion
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab | Experimental | Patients will receive 480mg of Nivolumab on a four weekly cycle for a maximum of two years. Receives: Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Durable Clinical Benefit
patient will be defined as experiencing DCB if they remain free of disease progression at their third trial specific CT scan since treatment start date (i.e. at approximately 27 weeks) or at any CT scan after 27 weeks that shows the patient remains free of disease progression
Measured: Beginning of trial treatment to free of disease progression (104 weeks maximum)
Secondary outcomes (5)
Objective Response
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) assessed by CT scan, objective response is the occurrence of Complete Response (CR) or Partial Response (PR) as the best overall response. Best overall response is the combined evaluation of target and non-target lesions, as provided in the protocol appendix 3.
Target lesions are evaluated as Complete Response (CR; disappearance of all target lesions), Partial Response (PR; >=30% decrease in the sum of the longest diameter), Progressive Disease (PD; >=20% increase in the sum of the longest diameter) or Stable Disease (SD; insufficient shrinkage for PR or insufficient increase for PD).
Non-target lesions are evaluated as Complete Response (CR; disappearance of all non-target lesions), Incomplete Response/Stable Disease (SD; persistence of non-target lesions) or Progressive Disease (PD; new lesions and/or progression of existing non-target lesions).
Measured: Trial treatment until disease progression (104 weeks maximum)
Best Percentage Change in Sum of Target Lesions
At each evaluation, the longest diameters of all selected target lesions will be measured and summed and the percentage change from the baseline measurement will be calculated. The best percentage change is the one that reflects either the greatest decrease or the least increase over the whole period of assessment.
Measured: Trial Treatment to disease progression (104 weeks maximum)
Time to Maximal Response
Time to maximal response was defined to be the time from commencement of trial treatment to the date of CT/MRI that first records objective response as per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) version 1.1.
Objective response is the occurrence of Complete Response (CR) or Partial Response (PR) as patient's best overall response (see Secondary Outcome: Objective Response).
Measured: Occurrence of CR or PR during the trial (104 weeks maximum)
Progression Free Survival Time
This is defined as the time from commencement of trial treatment to the date of CT scan when progressive disease first recorded or date of death without previously recorded progression.first records the best objective response as per RECIST version 1.1.
Measured: time from commencement of trial treatment to the date of CT scan when progressive disease first recorded (104 weeks maximum)
Overall Survival Time
This is defined as the time from commencement of trial treatment to the date of death from any cause.
Measured: Commencement of trial treatment until date of death; minimum of 18 months post-registration, if trial treatment was discontinued early, or up to 24 months post-registration for those completing trial treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2019
- Study start28 Aug 2019
- Primary completion26 Nov 2024
- Study completion26 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies 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
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Gary Middleton, MB,BS,FRCP, Principal investigator, University of Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03981146
- Sponsor's protocol ID
- RG_17-215
- Other IDs
- 2018-000318-39, 40245896, 2018
- Acronym
- ANICCA
- Status last verified
- Apr 2026
- First submitted
- 9 May 2019
- Last updated
- 22 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Middleton G, Gaskell C, Savage J, Bridgewater J, Ross P, Saunders M, Palmer D, Plummer R, Clive S, Coyle V, Thomas A, Cunningham D, Taniere P, Billingham L. Final results of ANICCA-Class II, a single arm, open-label phase II trial assessing nivolumab in tissue-specific class II expressing metastatic microsatellite stable colorectal cancer, with a parallel assessment of the immunoscore-immune checkpoint as a predictive biomarker for single-agent anti-PD-1. J Immunother Cancer. 2025 Dec 17;13(12):e012749. doi: 10.1136/jitc-2025-012749.
PubMed 41407398
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial Assessing Nivolumab in Class II Expressing Microsatellite Stable Colorectal Cancer
- ClinicalTrials.gov ID
- NCT03981146
- Acronym / sponsor ID
- ANICCA / RG_17-215
- Conditions
- Colorectal Cancer
- Keywords
- Class II Microsatellite Status
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- University of BirminghamUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 28 Aug 2019 (actual)
- Primary completion
- 26 Nov 2024 (actual)
- Study completion
- 26 Nov 2024 (actual)
- First posted
- 10 Jun 2019 (actual)
- Results
- Posted 22 Apr 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An open-label, single-arm, phase II, multicentre clinical trial to determine the rate of durable clinical benefit of nivolumab in patients with class II expressing microsatellite stable colorectal cancer.
Detailed description
Immuno-oncology is transforming the care of certain patients with cancer. Not all patients respond to these therapies however, and in some common cancers checkpoint blockade has failed to make any real impact. In 2014 there were over 41,000 new cases of colorectal cancer (CRC) in the UK and nearly 16,000 deaths from the disease, making it the second commonest cause of cancer death (Cancer Research UK Cancer Statistics Key Facts). 15% of patients with CRC develop it as a result of deficient mismatch repair (microsatellite instability - MSI): this cohort of patients respond well to PD-1/PD-L1 blockade as these tumours harbour a very high number of mutations thus increasing the likelihood of the presence of immunogenic neo-epitopes which elicit an immune response1. The majority of CRC patients, particularly those with metastatic disease (around 95%), do not display this hyper-mutator phenotype (microsatellite stable (MSS) CRC) and in these patients the results of PD-1/PD-L1 blockade have been disappointing.
In summary, MSS CRC patients with a class II expression appear to represent immunologically a group of MSI-like MSS patients that may respond to usefully to the immunotherapy agent nivolumab as a single agent and thus a trial of nivolumab in patients with class II expression of their cancer cells appears to be highly justified.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nivolumab | Experimental | Drug: NivolumabPatients will receive 480mg of Nivolumab on a four weekly cycle for a maximum of two years. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Histologically confirmed locally advanced or metastatic MSS CRC with class II expression (greater than 1% cancer cell positivity for class II expression on immunohistochemistry).
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (APPENDIX 1)
- Age ≥ 18 years
- Patients must have completed all standard of care therapy that the treating oncologist deems appropriate. Trial treatment as first line therapy is permitted if the patient has declined standard of care therapy.
- CT scan of chest, abdomen, pelvis within 28 days of registration demonstrating unidimensionally measurable disease as per RECIST version 1.1 (APPENDIX 3).
Key exclusion criteria (19 listed)
- Previous treatment with PD1/PDL1 inhibitors.
- with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
- Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Patient has risk factors for bowel obstruction or bowel perforation (examples include but not limited to a history of acute diverticulitis, intra-abdominal abscess and abdominal carcinomatosis).
- Patient has a known history of other malignancy, unless the patient has undergone potentially curative therapy with no evidence of that disease for 3 years.
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: Opdivo60 Minute IV Infusion | Drug | Nivolumab |
Primary outcome
Durable Clinical Benefit
Time frame: Beginning of trial treatment to free of disease progression (104 weeks maximum)
patient will be defined as experiencing DCB if they remain free of disease progression at their third trial specific CT scan since treatment start date (i.e. at approximately 27 weeks) or at any CT scan after 27 weeks that shows the patient remains free of disease progression
5 secondary outcomes
Objective Response
Time frame: Trial treatment until disease progression (104 weeks maximum)
Best Percentage Change in Sum of Target Lesions
Time frame: Trial Treatment to disease progression (104 weeks maximum)
Time to Maximal Response
Time frame: Occurrence of CR or PR during the trial (104 weeks maximum)
Progression Free Survival Time
Time frame: time from commencement of trial treatment to the date of CT scan when progressive disease first recorded (104 weeks maximum)
Overall Survival Time
Time frame: Commencement of trial treatment until date of death; minimum of 18 months post-registration, if trial treatment was discontinued early, or up to 24 months post-registration for those completing trial treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 41407398Middleton G, Gaskell C, Savage J, Bridgewater J, Ross P, Saunders M, Palmer D, Plummer R, Clive S, Coyle V, Thomas A, Cunningham D, Taniere P, Billingham L. Final results of ANICCA-Class II, a single arm, open-label phase II trial assessing nivolumab in tissue-specific class II expressing metastatic microsatellite stable colorectal cancer, with a parallel assessment of the immunoscore-immune checkpoint as a predictive biomarker for single-agent anti-PD-1. J Immunother Cancer. 2025 Dec 17;13(12):e012749. doi: 10.1136/jitc-2025-012749.
- Trial WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Gary Middleton, MB,BS,FRCP principal investigator
University of Birmingham
14 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 in people with Colorectal Cancer, run by University of Birmingham at 14 sites in United Kingdom.
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 17 inclusion and 19 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: finished, as of the sponsor's last update on 22 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United Kingdom. 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?
Yes. Results are posted in the registry (first posted 22 Apr 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Durable Clinical Benefit (time frame: Beginning of trial treatment to free of disease progression (104 weeks maximum)). 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 NCT03981146, which also lists 1 linked publication.
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 22 Apr 2026.