Condition category
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status

Plain English Summary

Lay summary under review with external organisation

Trial website

Contact information



Primary contact

Dr Siraj Takolia


Contact details

Cancer Research UK Clinical Trials Unit
University of Birmingham
Vincent Drive
B15 2TT
United Kingdom
+44 (0)121 414 6754



Additional contact

Dr Gary Middleton


Contact details

University of Birmingham
Institute of Cancer & Genomic Sciences
Vincent Drive
B15 2TT
United Kingdom
+44 (0)1214158237

Additional identifiers

EudraCT number

2018-000318-39 number

Nil known

Protocol/serial number


Study information

Scientific title

A phase II trial assessing nivolumab in strong class II expressing microsatellite stable colorectal cancer



Study hypothesis

The primary objective of this trial is to detect the rate of durable clinical benefit in patients with strong class II expressing microsatellite stable colorectal cancer treated with single agent nivolumab, to justify further investigation in subsequent studies.

The secondary objectives will be to evaluate the benefit to patients in terms of other clinical outcomes, to include:
1. Objective response rate
2. Best percentage change in sum of target lesion diameters
3. Time to maximal response
4. Progression free survival time
5. Overall survival time

Ethics approval

Approval pending, South Central – Oxford B Research Ethics Committee (White friars, Level 3, Block B, Lewins Mead, Bristol, BS1 2NT), ref: 19/SC/0107

Study design

Non-randomised; Interventional; Design type: Treatment, Screening, Immunotherapy

Primary study design


Secondary study design

Non randomised study

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet


Colorectal cancer


Informed consent:
Patients potentially suitable for the trial will be identified at an oncology clinic, and will be approached about the trial with the aid of the patient information sheet. After discussion about the trial and sufficient time to consider whether they wish to take part (usually at least 24 hours), the patient will be asked to sign an informed consent form in the presence of the research doctor. They will initially be provided with an information sheet explaining the purpose of the biopsy screening assessment and provide consent for this to be done. If MSS CRC with high class II levels are demonstrated they will then be provided with the information sheet for the main trial and provide further consent to take part.

Screening investigations:
Following the informed consent process, the patient will undergo screening assessments. These will include:
Full medical history - To include smoking and alcohol history, any relevant significant medical conditions (other than colorectal cancer) and autoimmune conditions, history of treatment for the primary diagnosis, including prior systemic treatment, radiation treatment and surgical treatment including best response to prior treatments where applicable.
Date of last prior cancer treatment must be documented. Radiographic studies performed prior to trial entry may also be requested for review.
1. Coagulation parameters: Prothrombin (PT) / International Normalised Ratio (INR) and partial thromboplastin (aPTT)
2. CT scan with contrast – chest, abdomen and pelvis within 28 days of planned treatment date (RECIST v1.1 reporting).
3. Hepatitis C Virus (HCV) RNA (qualitative), Hepatitis B Surface Antigen and Human Immunodeficiency Virus (HIV) 1 / 2 antibodies.

The following screening tests should be undertaken locally up to 7 days prior to trial registration:
1. Physical examination including height and weight
2. Vital signs - temperature, pulse, respiratory rate and blood pressure (average of 3 BP readings)
3. ECOG performance status
4. Adverse events - Adverse Events (AEs) and laboratory safety measurements will be graded per NCI Common Terminology Criteria for Adverse Events (CTCAE) version v4.03 . All adverse events, whether gradable by CTCAE or not, will also be evaluated for seriousness
5. Concomitant medications – taken within four weeks prior to registration.
6. Full blood count (FBC) to include: white blood cells, haematocrit, haemoglobin, platelets, neutrophils, lymphocytes, red blood cells, monocytes, basophils, eosinophils, absolute neutrophil count
7. Urinalysis
8. Pregnancy test if applicable (urine or serum β-HCG)
9. Comprehensive serum chemistry panel to include: sodium, potassium, urea, nitrogen, creatinine, magnesium, calcium (total), bilirubin (total), direct bilirubin, albumin, alkaline phosphatase (ALP), aspartate transferase (AST), alanine transferase (ALT), glucose, lactate dehydrogenase (LDH), phosphate, total protein, C reactive protein (CRP),
Carcinoembryonic antigen (CEA)
10. Renal function - Patients must have adequate renal function as defined by Creatinine clearance <1.5 x ULN concurrent with creatinine clearance >50 ml/min (calculated as per institutional standard)
11. Thyroid function and cortisol - analysis of cortisol, T3, T4 and Thyroid Stimulating Hormone (TSH)

Up to 24 hours to first treatment:
1. Urine pregnancy test, if cannot be confirmed as negative a serum test will be required

Nivolumab will be administered as a 60 minute IV infusion, with a window of -5 and +10 minutes, at a dose of 3 mg/kg on day 1 every 2 weeks. Patients will receive nivolumab for a maximum of 2 years and enter then enter the follow up period.

Routine and safety tests:
1. Physical examination including vital signs and measure of ECOG performance status
2. Routine blood samples for the analysis of haematology, biochemistry, thyroid function and cortisol
3. A CT scan of the chest, pelvis and abdomen
4. Adverse event review
5. Concomitant medication review

Research procedures:
1. A DNA sample (at baseline only)
2. ctDNA blood samples (at baseline, every 8 weeks and end of treatment)
3. Cytokine/chemokine and proteomics blood samples (at baseline, every 8 weeks and end of treatment)

Treatment discontinuation:
When a patient completes (or discontinues early) trial therapy, they will undergo the same tests performed throughout treatment at their end of treatment visit.
The timing of all investigations and sampling are detailed in the protocol and the relevant Patient Information Sheet.

Follow up:
A mandatory Safety Follow-Up Visit should be performed approximately 28 days after the last infusion of study medication, and include:
1. Physical examination including vital signs and measure of ECOG performance status
2. Routine blood samples for the analysis of haematology, biochemistry, thyroid function and cortisol
3. Renal function by calculation in the first instance, and measurement is permitted if required
4. Adverse event review
5. Concomitant medication review

For patients who begin another cancer therapy before 28 days after discontinuation of study therapy, the Safety Follow-Up Visit should occur prior to the patient receiving another cancer therapy.

Follow up data will be provided every 4 weeks up to 6 months post treatment discontinuation then every 12 weeks up to five years to obtain disease progression details (if patient discontinued for non-progression reasons), record treatment after progression and death date if applicable.

Intervention type



Phase II

Drug names


Primary outcome measure

Durable clinical benefit (DCB) defined as the occurrence of complete response (CR), partial response (PR) or stable
disease (SD) for 27 weeks or greater

Secondary outcome measures

1. Objective response: overall tumour burden assessed using RECIST version at CT scans every 9 weeks from trial entry up to 45 weeks, then every 12 weeks, until disease progression
2. Best percentage change in sum of target lesion diameters - 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.
3. Time to maximal response, defined as the time from commencement of trial treatment to the date of CT scan that first records the best objective response as per RECIST
4. Progression-free survival time, 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
5, Overall survival time, defined as the time from commencement of trial treatment to the date of death

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Histologically confirmed locally advanced or metastatic MSS CRC with strong class II expression (greater than 50% cancer cell positivity for class II expression on immunohistochemistry)
2. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
3. Age > = 18 years
4. 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
5. CT scan of chest, abdomen, pelvis within 28 days of registration demonstrating uni-dimensionally measurable disease as per RECIST version 1.1
6. Demonstrate adequate haematological function:
6.1. Platelet count > = 100 x 109 /L
6.2. Neutrophils > = 1.5 x 109/L
6.3. Haemoglobin > = 90 g/L
7. Demonstrate adequate hepatic function:
7.1. Serum bilirubin < = 1.5 x upper limit of normal (ULN)
7.2. Serum AST or ALT < = 2.5 x ULN or < 5 x ULN in the presence of liver metastases
8. Demonstrate adequate renal function:
8.1. Creatinine clearance < 1.5 times ULN and > 30ml/min (as per institutional standard)
9. Provision of signed and dated, written informed consent prior to any trial-specific procedures, sampling and analyses.
10. Negative pregnancy test (female patients of reproductive potential)
11. Patients must agree to the use of contraception

Participant type


Age group




Target number of participants

Planned Sample Size: 36; UK Sample Size: 36

Participant exclusion criteria

1. Previous treatment with PD1/PDL1 inhibitors
2. Untreated symptomatic brain or leptomeningeal metastatic disease
3. Medical or psychiatric conditions compromising informed consent
4. 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
5. Administration of chemotherapy, radioactive or biological cancer therapy within 4 weeks prior to the first dose of trial therapy
6. 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
7. Active autoimmune disease that has required systemic treatment in past 2 years (i.e. 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
8. 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
9. 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)
10. 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
11. Has a history of non-infectious pneumonitis requiring steroids or has active pneumonitis or significantly reduced transfer coefficient (KCO)
12. Female patients that are either pregnant or breastfeeding
13. Male and female patients (of childbearing age) not willing to use adequate contraception
14. Patient previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody
15. 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
16. Known history of tuberculosis
17. Patient has an active infection requiring therapy
18. Has received a live vaccine within 30 days prior to the first dose of trial treatment
19. 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)

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

University Hospitals Birmingham NHS Foundation Trust
Address Trust HQ PO Box 9551 Queen Elizabeth Medical Centre Edgbaston
B15 2TH
United Kingdom

Trial participating centre

NHS Greater Glasgow and Clyde
J B Russell House Gartnavel Royal Hospital 1055 Great Western Road
G12 0XH
United Kingdom

Trial participating centre

The Christie NHS Foundation Trust
550 Wilmslow Road Withington
M20 4BX
United Kingdom

Trial participating centre

University College London Hospitals NHS Foundation Trust
250 Euston Road
United Kingdom

Trial participating centre

Guy's and St Thomas' NHS Foundation Trust
Trust Offices Guy's Hospital Great Maze Pond
United Kingdom

Trial participating centre

Belfast Health & Social Care Trust
Knockbracken Healthcare Park Saintfield Road
United Kingdom

Trial participating centre

The Royal Marsden NHS Foundation Trust
Fulham Road
United Kingdom

Trial participating centre

Leeds Teaching Hospitals NHS Trust
St. James's University Hospital Beckett Street
United Kingdom

Trial participating centre

University Hospitals of Leicester NHS Trust
Leicester Royal Infirmary Infirmary Square
United Kingdom

Sponsor information


University of Birmingham

Sponsor details

Research Support Group
Aston Webb Building (B Block)
B15 2TT
United Kingdom
+44 (0)121 415 8011

Sponsor type




Funder type


Funder name

Bristol-Myers Squibb

Alternative name(s)

Bristol-Myers Squibb Company, BMS

Funding Body Type

private sector organisation

Funding Body Subtype

For-profit companies (industry)


United States of America

Results and Publications

Publication and dissemination plan

1. Peer reviewed scientific journals
2. Internal report
3. Conference presentation
4. Publication on website

IPD sharing statement
The datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.

Intention to publish date


Participant level data


Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

04/04/2019: Trial's existence confirmed by the NIHR.