Vedolizumab for the Prevention of ICI Related Diarrhea or Colitis in Patients With Cancer

VERIFY is a multicenter, prospective, randomized, double-blinded, placebo-controlled, parallel group superiority trial, evaluating the efficacy and safety of vedolizumab, a monoclonal antibody targeting the α4β7 integrin receptor specific to gut-targeted T-lymphocytes, for the prevention of ICI-related diarrhea and colitis in participants with unresectable melanoma, lung, or renal cancer starting immunotherapy who are at high risk, defined by the development of an elevated fecal calprotectin >100 μg/g within 4 weeks of the first ICI dose.

Eligible participants will be randomized 1:1 to receive 6 months of vedolizumab or placebo, administered as prophylaxis therapy in addition to continuing ICI treatment (administered at weeks 0, 2, 6, 14, and 22). Participants will then be followed for 1 year.

Inclusion criteria

• Signed informed consent prior to initiation of any study specific activities or procedures
• Adult patient ≥18 years old
• Diagnosed with unresectable advanced stage III or metastatic stage IV malignant melanoma, lung, or renal cancer
• Planned for initiation of SOC treatment with any immunotherapy and develop an elevated fecal calprotectin > 100 μg/g within 4 weeks of first ICI dose
• Ability to and willingness to adhere to the randomized treatment interventions (vedolizumab or placebo), administered intravenously
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test at the time of screening. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy or bilateral salpingectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes.
• As per the Health Canada product monograph, WOCBP are strongly recommended to use adequate contraception to prevent pregnancy and to continue its use for at least 6 months after the last study visit.

Note: abstinence is acceptable if this is established and preferred contraception for the patient and is accepted as a local standard.

Exclusion criteria

• Condition(s) for which vedolizumab is contraindicated (e.g., hypersensitivity reaction, known allergic reaction to vedolizumab or its components)
• Current or prior use of vedolizumab
• Presence of inflammatory bowel disease (Crohn's disease, ulcerative colitis), indeterminate colitis, segmental colitis associated with diverticulosis or microscopic colitis
• Presence of ileostomy, colostomy, or short bowel syndrome
• Presence of known luminal gastrointestinal metastases at baseline
• Presence of significant pre-existing autoimmune disease (at investigator's discretion)
• Presence of severe infection(s) or opportunistic infection(s)
• Active enteric infection with viral, bacterial, or parasitic pathogens
• Presence of untreated latent or active tuberculosis, or untreated chronic hepatitis B virus. If there is a clinical suspicion of either, it is at the discretion of the Investigator to order the appropriate work-up.
• Baseline ECOG status grade ≥3
• Pregnancy or lactation (no exclusion for pregnant partner)
• Treatment with another investigational product within 8 weeks of randomization
• Requirement for baseline anti-diarrheal treatment(s) (including but not limited to loperamide, diphenoxylate-atropine, octreotide, tincture of opium), anticholinergic drug(s), or opioid-based analgesic(s) used specifically for diarrhea control within 14 days of randomization
• Any condition or diagnosis, that could in the opinion of the Qualified Investigator or delegate interfere with the participant's ability to comply with study instructions, might confound the interpretation of the study results, or put the participant at risk