The goal of this clinical trial is to assess whether the early introduction of biological treatment with a TNF-alpha inhibitor (infliximab) in addition to corticosteroids for severe ir-colitis/diarrhoea will reduce the time to grade ≤ 1 ir-colitis/diarrhoea compared to corticosteroids alone in patients scheduled for ICI treatment for solid tumors and untreated mCTCAE grade 2-4 diarrhoea or colitis.

The main question it aims to answer is:

• Can an early introduction of biological treatment with a TNF-alpha inhibitor (infliximab) in addition to corticosteroids reduce the time to grade ≤ 1 ir-colitis/diarrhoea compared to corticosteroids alone.

Participants will be randomised 1:1:

Arm A: All patients will receive same dose of methylprednisolone i.v. daily. Arm B: Patients allocated to Arm B will in addition receive infliximab i.v. day 1 or 2.

Study patients are evaluated with blood samples, faecal samples and by sigmoidoscopy. Procedures are performed before randomisation and as part of follow up.

Inclusion Criteria

• Untreated mCTCAE grade 2-4 diarrhoea or colitis, or persistent mCTCAE grade 2 diarrhoea after administration of loperamide or equivalent for mCTCAE grade ≤ 2 diarrhoea

• No signs of colonic perforation or infection

• Age ≥ 18

• Understands the nature and purpose of the study and the study procedures and has signed informed consent

• Is able to read, understand, and complete questionnaires and daily components of the patient Diary for the study period

• Histologically confirmed malignant solid tumours

• Treatment with immune checkpoint inhibitors (anti-CTLA-4, anti-PD-1 or anti-PD-L1) within the past 12 weeks. Immune checkpoint inhibitors can be administered as single agents or as combination therapy with anti-CTLA-4 and anti-PD-1

• No probability of a concomitant treatment (e.g. laxatives) other than the immune checkpoint inhibitor being the causal drug for the colitis or diarrhoea

• Prior treatment with immune checkpoint inhibitors is allowed

• Usage of prednisolone ≤ 10 mg daily for non irAE is allowed

• Diagnostic work up including screening for viral hepatic infection and QuantiFERON-TB for mycobacterium tuberculosis must be requisitioned but will not need to be reported prior to study enrolment

• Women of child bearing potential must have a negative serum (preferred) or urine pregnancy test within 72 hours prior to registration.

  • Note: women of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e. females who have had evidence of menses in the past 12 months, with the exception of those who had prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight, ovarian suppression or other reasons.

• Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and after the study treatment:

  • for at least 6 months after the last study treatment, or depending on the duration antineoplastic treatment

  • Note: A highly effective method of birth control is defined as a method which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. Such methods include:

    • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal)
    • Progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable)
    • Intrauterine device (IUD)
    • Intrauterine hormone-releasing system (IUS)
    • Bilateral tubal occlusion
    • Vasectomized partner
    • Sexual abstinence

Exclusion Criteria

• Prior history of inflammatory bowel disease, colitis, or diarrhoea requiring treatment with any corticosteroid, or any other immunosuppressant medication
• Prior history of recurrent bowel disease including symptomatic diverticulosis
• Current positive testing for Clostridium difficile or other colonic infection
• Current bacterial infection requiring antibiotic treatment, or systemic fungal infection
• Ongoing antibiotic treatment for any reason
• Treatment with systemic corticosteroids within the last four weeks prior to study enrolment (daily usage of prednisolone ≤ 10 mg for non irAE conditions is accepted)
• Concurrent immune-related adverse events requiring immunosuppressant medication of any kind
• Known hypersensitivity or contraindications to systemic corticosteroids or infliximab
• Prior history of viral hepatitis with a positive viral load, known untreated mycobacterium tuberculosis, or known active herpes zoster infection

Prior to study initiation, the study will be registered at www.clinicaltrials.gov. No later than six months after Follow-up completion, a study report will be completed and data displayed on www.clinicaltrials.gov. Study results will be submitted to the Clinical Trials Information System (CTIS) portal as soon as possible and no later than one year after the trial has ended. In addition, the anonymised data will be made public available through the Zenodo open data repository (CERN), or an equivalent public database.

No later than one year after the trial has ended.