Mesothelioma

P3, N=53, Completed, Ferring Ventures Limited | Active, not recruiting --> Completed

P1/2, N=40, Active, not recruiting, Hospices Civils De Lyon | Recruiting --> Active, not recruiting

We identified cytarabine and methotrexate as significantly more effective in the 9p21 compromised BLCA cells. Analysis of morphological alterations further supported a genotype-specific activity of nucleoside analogs, nominating gemcitabine as a drug with greater efficacy in this context...Synergy between cytarabine and inhibitors of PRMT5 (MRTX1719) and MAT2A (AG-270) was mediated by a differential activation of DNA damage and replication stress markers, suggesting an exploitable vulnerability. In fact, rational drug combinations with ATR/CHK1 pathway inhibitors increased efficacy while maintaining 9p21-specificity. Finally, we confirmed the effectiveness of these combinations in cell models of pancreatic adenocarcinoma and pleural mesothelioma, two tumor types with high prevalence of MTAP loss and, most notably, in bladder cancer patient-derived organoids, underscoring the strong translational potential of our findings.

P1, N=60, Recruiting, Memorial Sloan Kettering Cancer Center

P2, N=28, Recruiting, Instituto do Cancer do Estado de São Paulo | Active, not recruiting --> Recruiting

P1/2, N=110, Terminated, Tango Therapeutics, Inc. | N=192 --> 110 | Active, not recruiting --> Terminated; Sponsor Decision - Business Decisions

TAMs were enriched in antigen-presentation (CD80, CD86, CXCL10), extracellular matrix-degradation (MMP9, CTSL), and CTL-suppression (ARG1, PLA2G7) pathways. Our analyses revealed that regional immunosuppression mediated by adaptive reprogramming of tumor-cell and immune-cell (TAMs, CTLs)-intrinsic changes-rather than by immune evasion or stromal exclusion-served as a mechanism of acquired resistance to dual-ICI therapy.

The CDK4/6 inhibitors abemaciclib and palbociclib have demonstrated promising results in patient-derived xenograft models of PM...While some cells showed sensitivity to Bcl-xL inhibitors, neither navitoclax nor the specific Bcl-xL inhibitor A-1331852, nor other BH3 mimetics targeting Bcl-2 (venetoclax) or Mcl-1 (S63845) increased cell death when combined with palbociclib...Therefore, we employed inhibitors of these pathways, such as dasatinib, momelotinib or Torin-1, which did not synergise with palbociclib to kill the cells...The differential effects of palbociclib and cisplatin on permanent growth arrest were verified by sorting PM cells based on size and β-galactosidase activity. Our findings underscore the importance of understanding the nature of therapy-induced senescence when assessing the effectiveness of senolytics in different tumour models.

The disease proved refractory to multiple lines of therapy, including platinum-based chemotherapy, immunotherapy, intrathoracic instillation and a subsequent individualized regimen comprising intraperitoneal cisplatin plus sintilimab for local disease control and potential immunomodulation synergized with oral anlotinib. It illustrates that rare but actionable genomic alterations, such as MET amplification, can be identified through liquid or tissue biopsy and can inform successful targeted treatment strategies, even in a tumor type where such alterations are uncommon. Histological classification combined with molecular profiling remains pivotal for personalized oncology.

P1, N=18, Completed, Vastra Gotaland Region | Active, not recruiting --> Completed

P=N/A, N=72, Completed, Travera Inc | Recruiting --> Completed | N=200 --> 72 | Trial completion date: Jul 2028 --> Mar 2026 | Trial primary completion date: Jul 2027 --> Mar 2026

Definitive diagnosis of primary greater omental malignant mesothelioma relies on pathology and immunohistochemistry. For unresectable cases, palliative surgery combined with individualized adjuvant therapy may achieve favorable short-term outcomes, highlighting the need for early clinical suspicion in patients with unexplained abdominal symptoms.