P2, N=210, Active, not recruiting, AbbVie | Recruiting --> Active, not recruiting

P1/2, N=32, Not yet recruiting, University of Aarhus

P2, N=60, Not yet recruiting, Mayo Clinic

The combination of spartalizumab and PDC, with or without canakinumab, was well tolerated across treatment groups. The antitumor activity across treatment groups was comparable with that of pembrolizumab and pemetrexed combination. Canakinumab did not appear to improve the antitumor activity when combined with spartalizumab, pemetrexed and cisplatin.

Moreover, DIA reduced TNF-α and caspase-3 protein expression. DIA attenuated AMD-induced pulmonary fibrosis via alleviating the TGF1/α-SMA/Smad3 pathway, reducing STAT-3 activation, and combating oxidative stress and inflammation in addition to promoting autophagy and abrogating apoptosis.

The original molecular glue degraders (thalidomide, lenalidomide, and pomalidomide) are known to bind to cereblon (CRBN) and alter its surface to induce recruitment, ubiquitination, and degradation of therapeutically valuable neosubstrates (IKZF1, IKZF3, and CK1α). Herein, we describe the medicinal chemistry efforts that resulted in the discovery of SJ3149 as well as other potent and selective CK1α degraders. We report kinetic profiling and parameters of CK1α degradation, ternary complex, antiproliferative effects, in vitro ADME data, and in vivo pharmacokinetic studies with demonstrated oral bioavailability.

Adult-onset Still's disease should be considered in the differential diagnoses of fever of undetermined origin. Early identification and initiation of treatment are critical to faster recovery and prevention of progression to severe complications. Steroids remain the standard first-line therapy and should be followed by disease-modifying steroid sparing drugs. The social determinants of health may preclude their timely initiation and should alert providers of proactive ways to avoid further delays.

P2, N=31, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | Trial completion date: Feb 2026 --> Nov 2024 | Trial primary completion date: Feb 2026 --> Oct 2024

P3, N=148, Recruiting, AO GENERIUM | Active, not recruiting --> Recruiting

These observations imply that Pomalidomide treatment influences the T-cell repertoire, particularly in the CD4 + subpopulation during the later stages of treatment, raising speculation about the potential involvement of these lymphocyte expansions in mechanisms related to antitumor immunity.

P2, N=180, Recruiting, Avalo Therapeutics, Inc.

P2, N=18, Recruiting, Novartis Pharmaceuticals | Trial completion date: Oct 2028 --> Jan 2031

P2, N=500, Recruiting, AbbVie | Not yet recruiting --> Recruiting

P2, N=120, Active, not recruiting, Zhejiang DTRM Biopharma | Recruiting --> Active, not recruiting

Persons with myeloma were randomized to receive an anti-TIGIT (T cell immunoreceptor) or anti-LAG3 (lymphocyte activation gene) antibody followed by combination with pomalidomide and dexamethasone ( NCT04150965 ). Anti-TIGIT responders had higher CD226 expression, natural killer cell activation and lower CD112 expression. These data demonstrate the clinical activity of TIGIT-LAG3 blockade and identify pathway-specific response correlates in myeloma.

P2, N=60, Recruiting, AbbVie | Not yet recruiting --> Recruiting

P1/2, N=50, Active, not recruiting, MediciNova | Trial completion date: Jun 2024 --> Dec 2024

P2, N=36, Completed, MediciNova | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Aug 2024

P2, N=120, Recruiting, Zhejiang DTRM Biopharma | Trial completion date: Mar 2024 --> Dec 2024 | Trial primary completion date: Mar 2024 --> Dec 2024

P2, N=23, Terminated, Novartis Pharmaceuticals | Completed --> Terminated; Sponsor Decision

P2, N=500, Not yet recruiting, AbbVie

Pomalidomide, which degrades IKZF1 and IKZF3, induced IFN-γ overproduction in human Treg cells. Mechanistically, the Foxp3-Ikzf1-Ikzf3 complex competed with epigenetic co-activators, such as p300, for binding to target gene loci via chromatin remodeling. Therefore, the Ikzf1 association with Foxp3 is essential for the gene-repressive function of Foxp3 and could be exploited to treat autoimmune disease and cancer.

P2, N=29, Recruiting, City of Hope Medical Center | Trial completion date: Jun 2024 --> Feb 2027 | Trial primary completion date: Jun 2024 --> Feb 2027

P2, N=157, Active, not recruiting, Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd. | Recruiting --> Active, not recruiting | Trial primary completion date: Jun 2024 --> Oct 2024

Formulation stored at 4 and 25±2 °C / 60±5 % relative humidity was stable for 3 months. Thus, the results demonstrated successful optimization of the transferosomes for the efficient topical delivery of berberine HCl and diacerein in the effective management of psoriasis.

P2, N=120, Recruiting, VA Office of Research and Development | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P1/2, N=41, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Jun 2024 --> Aug 2025

P1/2, N=101, Active, not recruiting, University of Chicago | Recruiting --> Active, not recruiting | Phase classification: P1b/2 --> P1/2

P2, N=75, Recruiting, Peter Shields | Not yet recruiting --> Recruiting | Initiation date: Sep 2023 --> Mar 2024

P2, N=60, Not yet recruiting, AbbVie

P2, N=23, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed

Enzyme inhibition experiments led to the discovery of the compound 10d, which exhibited moderate inhibitory potency (IC50 of 5.9 ± 0.7 μM), but unfortunately demonstrated no activity in D-DT degradation experiments. In conclusion, this study offers valuable insight into the SAR of D-DT inhibition, paving the way for the development of novel molecules as tools to study D-DT functions in tumor proliferation and, ultimately, new therapeutics for cancer treatment.

Osteoclasts with caspase-3-immunolabelled cytoplasm and nuclei with masses of condensed chromatin were observed in PDG, confirming osteoclast apoptosis. Diacerein inhibits osteoclastogenesis by decreasing Tnf and Il1b mRNA levels, resulting in decreased RANKL/OPG ratio, and induces apoptosis in osteoclasts of alveolar process of rat molars with periodontitis.

This case report emphasizes the diverse manifestations of TRAPS and the importance of recognizing gastrointestinal complications, particularly isolated colic amyloidosis. Comprehensive evaluation, including histological examination, is crucial for identifying atypical disease presentations and guiding management decisions. Continued research is needed to elucidate the underlying mechanisms and optimize treatment strategies for TRAPS and its associated complications.

Thus, while MSCs support the presence of these immature cell populations, they simultaneously inhibit their maturation. This finding provides novel mechanistic insights into lenalidomide- and pomalidomide-induced cytopenia, and could guide therapeutic strategies for its mitigation.

Furthermore, we develop a novel RALY protein degrader based on peptide proteolysis-targeting chimeras, named RALY-PROTAC, which we chemically synthesize by linking a RALY-targeting peptide with the E3 ubiquitin ligase recruitment ligand pomalidomide. In conclusion, our findings demonstrate a novel mechanism by which O-GlcNAcylation/RALY/USP22 mRNA axis aggravates HCC cells proliferation. RALY-PROTACs as degraders of the RALY protein exhibit potential as therapeutic drugs for RALY-overexpressing HCC.

Patients with treatment-naïve advanced pancreatic ductal adenocarcinoma (n=10) were treated with canakinumab, a high-affinity monoclonal human anti-interleukin-1β (IL-1β), the PD-1 blocking antibody spartalizumab, and gemcitabine/n(ab)paclitaxel. Within the tumor we observed few changes in suppressive myeloid-cell populations or activated T cells as assessed by single-cell transcriptional profiling or multiplex immunofluorescence, although increases in CD8+ T cells suggest that improvements in the tumor immune microenvironment might be revealed by a larger study. Overall, the data indicate that exposure to PD-1 and IL-1β blockade induced a modest reactivation of peripheral CD8+ T cells and decreased circulating monocytic MDSCs; however, these changes did not lead to similarly uniform alterations in the tumor microenvironment.

P2, N=40, Active, not recruiting, Fondazione IRCCS Policlinico San Matteo di Pavia | Recruiting --> Active, not recruiting | Trial completion date: Mar 2024 --> Jan 2025 | Trial primary completion date: Mar 2024 --> Nov 2024

P3, N=148, Active, not recruiting, AO GENERIUM

P3, N=56, Recruiting, University Hospital, Basel, Switzerland | Trial completion date: May 2024 --> May 2026 | Trial primary completion date: May 2024 --> May 2026

P2, N=23, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

P1, N=105, Completed, AO GENERIUM