P2, N=162, Not yet recruiting, Genentech, Inc.

P1/2, N=10, Not yet recruiting, Zomagen Biosciences Limited

P2, N=36, Recruiting, Cambridge University Hospitals NHS Foundation Trust | Not yet recruiting --> Recruiting | Initiation date: Nov 2025 --> Feb 2026

Emerging strategies to modulate NLRP3 include small-molecule inhibitors (e.g., MCC950, BAY-117082), plant-derived compounds (e.g., oridonin, Bacopa monnieri), and immunotherapy approaches, including intratumoral NLRP3 agonists combined with checkpoint blockade. This review synthesizes the multifaceted roles of NLRP3 in OSCC, highlighting its centrality in inflammation-driven tumor biology and its promise as a therapeutic target. Understanding the contextual duality of NLRP3 activation is critical for developing precision therapies that disrupt its tumor-supportive effects while preserving or enhancing its immunogenic functions.

P2, N=0, Withdrawn, Halia Therapeutics, Inc. | N=50 --> 0 | Trial completion date: Aug 2026 --> Jan 2026 | Recruiting --> Withdrawn | Trial primary completion date: Aug 2026 --> Jan 2026

P1, N=59, Active, not recruiting, Novartis Pharmaceuticals | N=105 --> 59

P2, N=210, Active, not recruiting, Shaperon | Recruiting --> Active, not recruiting | Trial completion date: Mar 2026 --> Aug 2026 | Trial primary completion date: Oct 2025 --> Jun 2026

This study reveals that ETS1 transcriptionally suppresses NKIRAS1, activating NF-κB signaling and promoting pyroptosis and pancreatic injury in AP. Targeting ETS1 may represent a promising therapeutic strategy.

P1, N=53, Recruiting, Nodthera Limited

P1/2, N=66, Not yet recruiting, AstraZeneca AB

P1, N=78, Recruiting, AC Immune S.A.

Nanoprodrugs orchestrate a sophisticated cascade of immune activation through four synergistic mechanisms: 1) size-switchable disassembly upon glutathione/ cholesterol exposure for deep tumor penetration; 2) redox imbalance driven by reactive nitrogen species accumulation and glutathione depletion via the synergistic action of oxaliplatin, ferrocene, and RRx-001 for ferroptosis augmentation; 3) immunogenic cell death induction via ferroptosis-apoptosis to initiate tumor immunity cycle, promoting T cell infiltration; and 4) T cell function reinvigoration with the downregulation of programmed cell death protein 1 and T-cell immunoglobulin 3 expression through cholesterol depletion in TME. This integrated approach achieved primary and distant tumor growth suppression, established durable immune memory against recurrence, and systemically enhanced the antitumor immunity. By concurrently targeting tumor immunogenicity, TME immunosuppression, and T cell exhaustion, this multidimensional strategy represents a transformative advancement in cancer immunotherapy.