P1/2, N=45, Not yet recruiting, Ziauddin University

P=N/A, N=120, Enrolling by invitation, Mayo Clinic | Not yet recruiting --> Enrolling by invitation

P4, N=21, Recruiting, Mayo Clinic | Trial completion date: Feb 2025 --> Mar 2026 | Trial primary completion date: Feb 2025 --> Mar 2026

P=N/A, N=400, Active, not recruiting, Bristol-Myers Squibb

P2, N=214, Recruiting, Fujian Medical University Union Hospital | Trial completion date: Dec 2024 --> May 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P1, N=24, Completed, Merck Sharp & Dohme LLC

P2, N=113, Active, not recruiting, Keros Therapeutics, Inc. | Trial completion date: Jan 2027 --> Mar 2025 | Trial primary completion date: Jun 2025 --> Mar 2025

In this trial, the combination of PDS0101, PDS01ADC, and bintrafusp alfa showed an acceptable safety profile and promising antitumor activity and improved OS in patients with HPV-16-positive cancers, in both ICB-naive and ICB-resistant patients, warranting further evaluation of the combination of PDS0101 and PDS01ADC with simultaneous PD-L1/TGF-β inhibition in these populations.

Only two FDA-approved medications, pirfenidone and nintedanib, are available. Emerging research has highlighted that numerous flavonoids derived from traditional medicines can inhibit the critical regulators responsible for activating the NLRP3 inflammasome. These flavonoids show promise as potential therapeutic agents for managing IPF, offering a new avenue for treatment that targets the core inflammatory processes of this debilitating condition.

P1, N=48, Completed, H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting --> Completed

P3, N=444, Active, not recruiting, Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA | Recruiting --> Active, not recruiting | Trial completion date: Dec 2029 --> Apr 2025 | Trial primary completion date: Aug 2026 --> Apr 2025

This analysis of 331 luspatercept real-life-treated LR-MDS patients demonstrated a significant OS benefit upon luspatercept response. Low baseline RBC-TB and lower risk IPSS-M scores correlated with higher HI and could constitute predictive markers of response.

P2, N=90, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Jul 2025 --> Aug 2026 | Trial primary completion date: Feb 2025 --> Aug 2025

M6223±BA had a manageable safety profile, with RDEs defined for both monotherapy and combination therapy. Further evaluation of M6223 is ongoing in combination with the PD-L1 inhibitor avelumab in patients with advanced urothelial carcinoma (JAVELIN Bladder Medley; NCT05327530).

P2, N=130, Not yet recruiting, Merck Sharp & Dohme LLC

P2, N=70, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting --> Recruiting

Pirfenidone was administered at doses of 100, 200, and 300 mg/kg, orally, with sodium valproate as a standard drug...Pirfenidone shows potential as an anticonvulsant, anti-inflammatory, hepatoprotective, and neuroprotective agent, with additional benefits in improving cognition and oxidative stress profiles in epilepsy treatment. Further studies are required to explore its long-term safety and efficacy.

CAFs activate neutrophils and enhance the malignant phenotype of pancreatic cancer. The interactions between cancer cells, CAFs, and neutrophils can be disrupted by PFD, highlighting a potential therapeutic approach.

P2, N=240, Active, not recruiting, PureTech | Trial completion date: Aug 2025 --> Dec 2025

Single-cell sequencing demonstrated that JS-201 reduced fibroblast proliferation by inhibiting the TGF-β/Smad pathway and the release of neutrophil extracellular traps mediated by ROS, thereby relieving radiation-induced pulmonary fibrosis. In conclusion, the JS-201 and radiotherapy combination enhances antitumor effects while mitigating acute and chronic RILI, and it may have potential for translational investigation as a cancer treatment strategy.

P2, N=120, Recruiting, Keros Therapeutics, Inc. | Trial completion date: Jun 2025 --> Jan 2029 | Trial primary completion date: Apr 2025 --> Dec 2026

P2/3, N=650, Recruiting, Bicara Therapeutics

P2, N=50, Not yet recruiting, Weill Medical College of Cornell University

P2, N=14, Not yet recruiting, Bastiaan Driehuys | Initiation date: Dec 2024 --> Mar 2025

Here, we report the synthesis and characterization of HYL001, a potent inhibitor of TGFβ receptor 1 (ALK5), that is approximately 9 times more efficacious than the structurally related compound galunisertib, while maintaining a favorable safety profile. HYL001 in combination with immune checkpoint blockade (anti-PD1) eradicates liver metastases generated in mice by microsatellite stable, aggressive colorectal cancer tumors at doses where galunisertib is ineffective.

A dry powder inhalation formulation called COS-2080-DPI has been developed using the ultrasonic spray freeze drying (USFD) technique, demonstrating significant antifibrotic efficacy in mice with bleomycin-induced PF at a dosage approximately 600 times lower than pirfenidone. Moreover, COS-2080 effectively attenuated fibrosis in MRC-5 cells by activating the cAMP/protein kinase A (PKA)/CREB pathway and potentially increasing levels of p53 protein. Our findings suggest that effective inhibition of PDE10A potentially confers a protective effect on FMT in PF by impeding TGF-β signaling and activating the cAMP/PKA/CREB/p53 axis.

Seventy-two SD rats were randomly divided into the control group, model group, pirfenidone group(162 mg·kg~(-1)), and low-, medium-and high-dose of Fuzheng Tongluo Granules groups(2.63, 5.25, 10.5 g·kg~(-1)). Rat model of IPF was induced by a single non-invasive tracheal intubation drip of bleomycin(BLM)...There was a high degree of co-localization between GSDMD and CD68. In summary, Fuzheng Tongluo Granules can effectively reduce pulmonary fibrosis and inflammation levels in rats with IPF, and the mechanism may be related to the down-regulation of the NLRP3/caspase-1/GSDMD pathway to inhibit macrophage pyroptosis.

P2, N=50, Recruiting, Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd.

P3, N=309, Active, not recruiting, Celgene | Trial completion date: Aug 2025 --> Feb 2029

P3, N=225, Recruiting, Keros Therapeutics, Inc. | Not yet recruiting --> Recruiting | Trial primary completion date: Mar 2032 --> Mar 2028

P2, N=5, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting | N=70 --> 5

P=N/A, N=120, Not yet recruiting, Mayo Clinic

P1/2, N=156, Recruiting, Corbus Pharmaceuticals Inc. | Not yet recruiting --> Recruiting

On the basis of an interim analysis, the data were considered mature, and no further analysis has been planned. Bintrafusp alfa with chemotherapy was found to have a manageable safety profile and encouraging clinical activity in patients with stage IV NSCLC.

P3, N=172, Active, not recruiting, Acceleron Pharma, Inc., a wholly-owned subsidiary of Merck & Co., Inc., Rahway, NJ USA | Trial completion date: Nov 2025 --> Feb 2025 | Trial primary completion date: Sep 2025 --> Jul 2024

P2, N=249, Recruiting, Bristol-Myers Squibb | Trial primary completion date: Nov 2025 --> Jul 2027 | Trial completion date: Jun 2026 --> Aug 2034

P2, N=99, Recruiting, Celgene | Trial completion date: Nov 2026 --> Jun 2035 | Trial primary completion date: Jun 2026 --> Jul 2027

P1, N=100, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2024 --> Dec 2027 | Trial primary completion date: Dec 2024 --> Dec 2027

P1/2, N=222, Recruiting, Suzhou Zelgen Biopharmaceuticals Co.,Ltd | Trial primary completion date: Nov 2024 --> Nov 2025

P1, N=50, Not yet recruiting, FBD Biologics Limited | Initiation date: Sep 2024 --> Jan 2025

P2, N=70, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Sep 2024 --> Jun 2025

Luspatercept, which can reduce SMAD2/SMAD3-dependent signaling implicated in suppression of erythropoiesis, may obviate the need for red blood cell transfusion in MDS-RS for more than a year, thereby diminishing further iron loading. However, luspatercept cannot be expected to substantially reduce the existing iron overload.