A Phase II Trial Assessing Nivolumab in Class II Expressing Microsatellite Stable Colorectal Cancer

NCT03981146 | Completed Phase 2 Results

• 3 other identifiers: RG_17-2152018-000318-3940245896
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 14

Brief 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.

Conditions

Colorectal Cancer

Keywords

Class II Microsatellite Status

Outcome Measures

Primary Outcomes (1)

• 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

  Beginning of trial treatment to free of disease progression (104 weeks maximum)

Secondary Outcomes (5)

• Objective Response

  Trial treatment until disease progression (104 weeks maximum)

• Best Percentage Change in Sum of Target Lesions

  Trial Treatment to disease progression (104 weeks maximum)

• Time to Maximal Response

  Occurrence of CR or PR during the trial (104 weeks maximum)

• Progression Free Survival Time

  time from commencement of trial treatment to the date of CT scan when progressive disease first recorded (104 weeks maximum)

• Overall Survival Time

  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.

Study Arms (1)

Nivolumab

EXPERIMENTAL

Patients will receive 480mg of Nivolumab on a four weekly cycle for a maximum of two years.

Drug: Nivolumab

Interventions

Nivolumab DRUG

60 Minute IV Infusion

Also known as: Opdivo

Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of Birmingham: lead
• Bristol-Myers Squibb: collaborator

Study Sites (14)

Belfast City Hospital

Belfast, United Kingdom

Location

Queen Elizabeth Hospital

Birmingham, United Kingdom

Location

Velindre Cancer Centre

Cardiff, United Kingdom

Location

Western General Hospital

Edinburgh, United Kingdom

Location

St James Leeds

Leeds, LS9 7TF, United Kingdom

Location

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

Clatterbridge Cancer Centre

Liverpool, United Kingdom

Location

The Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Guys Hospital

London, United Kingdom

Location

The Royal Marsden NHS Foundation Trust

London, United Kingdom

Location

University College Hospital

London, United Kingdom

Location

The Christie Hospital, The Christie NHS Foundation Trust

Manchester, United Kingdom

Location

Freemans Hospital

Newcastle upon Tyne, United Kingdom

Location

Weston Park

Sheffield, S10 2SJ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 41407398 RESULT

Related Links

• Trial Website

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: ANICCA-Class II Trial Coordinator
• Organization: Cancer Research UK Clinical Trials Unit, University of Birmingham

anicca-classii@trials.bham.ac.uk

0121 414 8040

Study Officials

• Gary Middleton, MB,BS,FRCP

  University of Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2019
• First Posted: June 10, 2019
• Study Start: August 28, 2019
• Primary Completion: November 26, 2024
• Study Completion: November 26, 2024
• Last Updated: April 22, 2026
• Results First Posted: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (14)