The INTEGRIS-IPF trial evaluated the safety, tolerability, and potential antifibrotic effects of bexotegrast (PLN-74809) in patients with idiopathic pulmonary fibrosis (IPF). Bexotegrast is an oral, once-daily investigational drug that blocks the activation of transforming growth factor beta (TGF-β) by preventing integrins αvβ6 and αvβ1 from binding to the latent TGF-β. The study was a Phase-2a, multicenter, randomized, double-blind, dose-ranging, placebo-controlled trial involving 119 participants with IPF. Participants were randomized to receive bexotegrast at 40, 80, 160, or 320 mg or placebo, with or without background therapy (pirfenidone or nintedanib). The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs), while exploratory endpoints included changes in forced vital capacity (FVC), quantitative lung fibrosis (QLF) extent, and fibrosis-related biomarkers. Bexotegrast was well tolerated, with similar rates of TEAEs in the bexotegrast and placebo groups. The most common TEAE was diarrhea, which was more frequent in participants receiving nintedanib. Participants treated with bexotegrast experienced a reduction in FVC decline over 12 weeks compared with those receiving placebo, with or without background therapy. A dose-dependent antifibrotic effect was observed, with a decrease in fibrosis-associated biomarkers compared with placebo. The study found that bexotegrast demonstrated a favorable safety and tolerability profile up to 12 weeks. Exploratory analyses suggested an antifibrotic effect based on FVC, QLF imaging, and circulating levels of fibrosis biomarkers. The results indicate that bexotegrast may be a promising treatment for IPF, with further studies needed to confirm its efficacy and safety.The INTEGRIS-IPF trial evaluated the safety, tolerability, and potential antifibrotic effects of bexotegrast (PLN-74809) in patients with idiopathic pulmonary fibrosis (IPF). Bexotegrast is an oral, once-daily investigational drug that blocks the activation of transforming growth factor beta (TGF-β) by preventing integrins αvβ6 and αvβ1 from binding to the latent TGF-β. The study was a Phase-2a, multicenter, randomized, double-blind, dose-ranging, placebo-controlled trial involving 119 participants with IPF. Participants were randomized to receive bexotegrast at 40, 80, 160, or 320 mg or placebo, with or without background therapy (pirfenidone or nintedanib). The primary endpoint was the incidence of treatment-emergent adverse events (TEAEs), while exploratory endpoints included changes in forced vital capacity (FVC), quantitative lung fibrosis (QLF) extent, and fibrosis-related biomarkers. Bexotegrast was well tolerated, with similar rates of TEAEs in the bexotegrast and placebo groups. The most common TEAE was diarrhea, which was more frequent in participants receiving nintedanib. Participants treated with bexotegrast experienced a reduction in FVC decline over 12 weeks compared with those receiving placebo, with or without background therapy. A dose-dependent antifibrotic effect was observed, with a decrease in fibrosis-associated biomarkers compared with placebo. The study found that bexotegrast demonstrated a favorable safety and tolerability profile up to 12 weeks. Exploratory analyses suggested an antifibrotic effect based on FVC, QLF imaging, and circulating levels of fibrosis biomarkers. The results indicate that bexotegrast may be a promising treatment for IPF, with further studies needed to confirm its efficacy and safety.