nintedanib

P=N/A, N=88, Active, not recruiting, Boehringer Ingelheim | Terminated --> Active, not recruiting | Trial completion date: Sep 2025 --> Apr 2026 | Trial primary completion date: Sep 2025 --> Apr 2026

Furthermore, Ofev inhibited fibroblast-to-myofibroblast transition by downregulating α-smooth muscle actin (α-SMA) expression and restored physiological type I/III collagen ratios, yielding regenerated skin morphologically and functionally comparable to normal tissue. Critically, this study provides the first direct evidence linking PFTs clearance to scar prevention, establishing a novel therapeutic paradigm for drug-resistant wound infections through the coordinated actions of detoxification, antimicrobial intervention, and fibrosis suppression.

P4, N=20, Not yet recruiting, The Affiliated Hospital of Qingdao University

P=N/A, N=586, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Sep 2026 --> Jun 2026

Adding nintedanib to anti-PD-1 mAb therapy significantly inhibited in vivo tumor progression. These results indicate that nintedanib suppresses MDSCs and CAFs by inhibiting VEGFR-, PDGFR-, and FGFR-mediated signaling, thereby increasing effector T-cell infiltration into tumors and enhancing the anti-tumor effects of αPD-1 mAb therapy.

P1, N=57, Not yet recruiting, Endeavor Biomedicines, Inc.

We evaluated the antitumor effect of the combination therapy with osimertinib and either nintedanib (an indirect TGF-β inhibitor) or vactosertib (a specific TGF-β type I receptor kinase inhibitor). In conclusion, combination therapy with osimertinib and TGF-β inhibitors potentiates osimertinib-induced antitumor immunity. These findings highlight a novel therapeutic strategy for EGFR-mutated NSCLC and warrant further clinical investigation.

Standard-of-care treatments (pirfenidone, nintedanib) reduced FUS expression in PCLs. In contrast, ION363 promoted functional marker expression and improved morphology in patient-derived 3D alveolospheres. We conclude that FUS is a pivotal regulator of fibrotic signaling in IPF and that targeting FUS via ASO represents a promising therapeutic avenue for IPF.

His condition worsened despite high-dose steroids, cyclophosphamide, and plasma exchange; he required ECMO and died after 40 days...He was treated with steroids, rituximab, nintedanib, and mycophenolate...This case series highlights the full clinical spectrum, from pediatric onset to fulminant adult disease. Multidisciplinary care, awareness of atypical presentations, and continued research into disease mechanisms and therapeutics are essential to improving survival in MDA5-DM.

Combination of nivolumab and nintedanib was shown to be safe and feasible. Despite missing synergistic effects on efficacy for the overall population, promising OS was observed for patients with high PD-L1 expression and for patients with previous immunotherapy. Therefore, CPI responsiveness may have been restored in some cases. Inhibition of FGFR-mediated tumor progression seems relevant in tumors with lower levels of both PD-L1 and FGFR1 expression and might be effectively inhibited by nintedanib. The combination nivolumab/nintedanib might warrant further exploration in selected patients.

Few FDA approved drugs (such as Sorafenib, Sunitinib, Nintedanib and Cabotanzinib), which target VEGFRs, however, a significant issue with the monotherapy of these agents is drug resistance. Finally, in silico molecular docking studies on VEGFR-2 (PDB ID 3VHE) revealed that compounds 5d, 5j, and 5q showed encouraging inhibition constants (68.5-154.92 nM) and binding energies (-9.29 to -9.77 kcal/mol) compared to Sunitinib (inhibition constant = 248.72 nM) and binding energy = -9.01 kcal/mol). Specifically, compounds 5d and 5j established an H-bond with the ASP1046 residue, similar to the standard drug Sunitinib.

The antifibrotic agents pirfenidone and nintedanib, thought to work primarily through suppression of TGF-β function, are used routinely in clinical practice for non-pancreatic indications, with a first trial in pancreatitis underway. Trials evaluating these licensed therapeutics that include primary diabetes-related endpoints and measures aiming to elucidate the underlying mechanisms of action merit consideration in type 3c diabetes and ultimately in type 2 diabetes and in combinatorial regimens in type 1 diabetes.