OnCo
ideasIdea

Randomise a cheap antihistamine alongside immunotherapy

Patients who happened to take common allergy pills during immunotherapy seemed to live longer in a large records study. A simple randomised trial would show whether the pills really help.

A 2022 analysis of MD Anderson records (Li and colleagues, Cancer Cell) found that H1-antihistamine use during checkpoint inhibitor therapy was associated with improved survival in melanoma and lung cancer, with mechanistic work suggesting histamine-HRH1 signalling in macrophages drives T-cell dysfunction. Antihistamines cost pennies and are extremely safe. The proposal is a placebo-controlled randomised trial of a non-sedating H1-antihistamine (for example fexofenadine or loratadine) added to standard checkpoint inhibitor therapy in non-small cell lung cancer, with a plasma histamine biomarker sub-study.

Hypothesis
Adding an H1-antihistamine to first-line checkpoint inhibitor therapy improves progression-free survival with a hazard ratio of 0.8 or better, with the effect concentrated in patients with high plasma histamine.
Rationale
The observational effect size was large, a mechanism has been demonstrated in mice, and the intervention has essentially no cost or toxicity, making the expected value of a trial very high even at modest prior probability.
What would test it
Phase 2/3 randomised double-blind trial of roughly 600 patients with NSCLC starting pembrolizumab-based therapy, PFS primary endpoint, biomarker-stratified analysis.
Maturity
preclinical evidence
Who has to act
research
Cost to try
Medium ($1M to $50M)
Years to first evidence
4
Bottlenecks it attacks

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