Inhaled budesonide to prevent recurrent checkpoint inhibitor–related pneumonitis

Inhaled Budesonide for REcurrence Prevention and Adjuvant THerapy in Checkpoint Inhibitor Pneumonitis

This study tests whether adding inhaled budesonide to usual care can prevent recurrence of pneumonitis in adults who developed grade 2 or higher lung inflammation from checkpoint inhibitor immunotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 94 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: AHS Cancer Control Alberta (Academic / other)
• Drugs / interventions: chemotherapy, prednisone, immunotherapy
• Locations: 1 site (Calgary, Alberta)
• Trial ID: NCT06860542 on ClinicalTrials.gov

What this trial studies

This phase 2 interventional trial compares inhaled budesonide plus usual care versus usual care alone for adults with a first episode of grade ≥2 checkpoint inhibitor pneumonitis (CIP). Eligible participants have histologically confirmed solid tumors and a CIP diagnosis made according to ASCO/ESMO guidance after ruling out infection and cancer progression. The budesonide arm uses Pulmicort Turbuhaler in addition to standard management, and outcomes include recurrence rate, systemic steroid exposure, safety, and ability to continue cancer therapy. Participants will undergo clinical follow-up and imaging as indicated to monitor lung inflammation and exclude other causes.

Who should consider this trial

Good fit: Ideal candidates are adults with solid tumors receiving checkpoint inhibitors who have a first documented episode of grade 2 or higher CIP and can attend the Calgary study site.

Not a fit: Patients with lung inflammation due to infection or tumor progression, those with contraindications to inhaled corticosteroids, or those with chronic steroid‑refractory pneumonitis may not benefit from this approach.

Why it matters

Potential benefit: If successful, inhaled budesonide could reduce pneumonitis recurrence, lower systemic steroid use, and help patients remain on cancer immunotherapy with better quality of life.

How similar studies have performed: This approach is relatively novel—systemic corticosteroids are the standard treatment for CIP and inhaled corticosteroids have limited prior data specifically for preventing CIP recurrence, though they are used in other airway inflammatory conditions.

Eligibility criteria

Inclusion Criteria:

1. Patients must be 18 years of age, or older on the day of signing informed consent and be willing and able to provide written informed consent/assent and, in the opinion of the Investigator, comply with protocol tests and procedures
2. Patients require histologically confirmed solid tumour undergoing immune checkpoint inhibitor (ICI) therapy
3. Diagnosis of first documented diagnosis of Checkpoint Inhibitor Pneumonitis (CIP) made per European Society for Medical Oncology (ESMO)/American Society for Medical Oncology (ASCO) guidelines with severity \>/grade 2 by Common Terminology Criteria for Adverse Events (CTCAE)v5.0

   a. Per ASCO/ESMO consensus guidelines, workup must include a compatible clinical picture, plus/minus supporting radiographic evidence (chest x-ray or preferably computed tomography (CT)), combined with clinical and/or microbiologic ruling out of alternative etiologies including infections or pulmonary disease progression. This includes a negative COVID test. Bronchoscopic sampling is not required, but can be considered.
4. Be able to effectively operate and use budesonide delivery method (Turbuhaler®), either independently or with aid of caregiver who anticipates being able to do so throughout trial period
5. Have adequate organ function, as judged by enrolling clinician
6. Females of childbearing potential have a negative urine or serum pregnancy test prior to study day 1. Patients of childbearing potential are those who have not been surgically sterilized or have not been free of menses for at least 1 year
7. Females of childbearing potential are willing to use contraception or abstain from heterosexual sexual contact for the course of the study

Exclusion Criteria:

1. Diagnosis of interstitial lung disease (ILD) active (clinically and radiologically evident) within last year prior to diagnosis of CIP
2. Clinically suspected significant lung disease for which inhaled steroid would be standard of care (moderate asthma or severe chronic obstructive pulmonary disease (COPD)) and for which randomization to no inhaled steroids (control arm) would not represent optimal medical care. Based on enrolling physicians judgement; spirometry/pulmonary function tests are NOT required to assess this exclusion criteria.
3. Current (within last two weeks), active (not medically able or unwilling to discontinue prior to treatment start) and regular (2 or more times per week) use of inhaled steroids (for any indication) or systemic (\>10mg prednisone equivalent) corticosteroids (for indication other than CIP) at time of randomization
4. Receiving systemic, non-chemotherapy immunosuppressive agent at time of randomization (hydroxychloroquine is acceptable)
5. Use of a medication with significant interaction with inhaled budesonide (HIV protease inhibitors, ketoconazole or other potent CYP3A4 inhibitors), unless deemed required and safe by co-investigator.
6. Known poorly controlled diabetes, defined as A1c \>10, prior to initiation of steroids for CIP
7. History of active and unstable systemic disease, including heart failure New York Heart Association (NYHA) III or IV, cirrhosis with Child Pugh B or C, Renal Failure with creatinine clearance (CrCl) \<30 per Cockcroft-Gault formula, or other unstable life limiting condition as determined by trial investigators
8. Current or prior participation in a study of an investigational agent or device within 4 weeks of randomization
9. History or current evidence of any condition, therapy, or laboratory abnormalities which might confound trial results, interfere with the patient's participation for the full duration of the trial, or otherwise causing it to be not in the best interest of the patient to participate in the trial, in the opinion of the treating investigator.
10. Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is directly involved with this trial, unless prospective ethics board approval (by chair or designee) is given allowing exception to this criterion for a specific patient
11. Breastfeeding is not permitted during the duration of trial participation.

Where this trial is running

Calgary, Alberta

• Arthur J.E. Child Comprehensive Cancer Centre — Calgary, Alberta, Canada (Recruiting)

Study contacts

• Study coordinator: Alexander Watson, MD

Conditions Pneumonitis; Immune-related Adverse Event; Checkpoint Inhibitor Pneumonitis