In the KPC mouse model of PDAC, pharmacologic induction of MHC-II expression by cobimetinib treatment in malignant epithelial cells significantly enhanced the therapeutic response to immune checkpoint blockade (ICB)...Our results position MHC-II as a promising prognostic biomarker and therapeutic target in PDAC, paving the way for novel immunomodulatory strategies. Single-cell and spatial transcriptomic analyses reveal that elevated MHC-II expression in malignant PDAC cells correlates with increased infiltration of CD4⁺ and CD8⁺ T cells.Stimulating MHC-II expression in tumors effectively enhances immunotherapeutic responses to ICB in the PDAC KPC mouse model, including PDAC tumors previously resistant to therapeutic interventions.MHC-II serves as a prognostic biomarker and a promising target for immunotherapy in PDAC.

P2, N=29, Recruiting, University of Utah | Trial primary completion date: Aug 2025 --> Jan 2026

P=N/A, N=20, Completed, Beijing Childrens Hospital,Capital Medical University; Beijing Childrens Hospital,Capital Medical University

P1, N=15, Active, not recruiting, OHSU Knight Cancer Institute | Recruiting --> Active, not recruiting

Luvometinib had a manageable safety profile in pediatric patients with unresectable NF1-related PN. Encouraging preliminary efficacy was observed, particularly among patients receiving the RP2D of 5 mg/m2, supporting further investigation of luvometinib in this setting.

In summary, our study characterized a significantly more invasive phenotype of double-resistant cell lines compared to melanoma cells sensitive to BRAF and MEK inhibitors. Successful inhibition of this phenotype could result in more effective therapy and thus a better prognosis for patients.

While BRAF mutations are common in ECD, RAS isoforms occur in a smaller subset. This case highlights RAS-positive ECD, managed with KRAS pathway-targeted MEK inhibition, in line with the 2019 ECD Medical Symposium recommendations.

P2, N=51, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Jul 2026 --> Jul 2025

P1/2, N=16, Active, not recruiting, Massachusetts General Hospital | Trial completion date: Jan 2027 --> Jan 2031 | Trial primary completion date: Jan 2025 --> Jan 2029

We found that both cobimetinib and daytime RMC-4550 similarly reduced tumor volume. Diurnal patterns of monocyte trafficking were disrupted in tumor-bearing mice, and SHP2 inhibition reduced tumor volume only when administered during the day, when myeloid infiltration was low. These findings suggest that SHP2 inhibitor-driven tumor shrinkage requires targeting monocyte-derived macrophages and is influenced by the timing of drug administration.

P1, N=3, Active, not recruiting, City of Hope Medical Center | Suspended --> Active, not recruiting

Mirdametinib offers an effective, targeted, and orally available treatment for NF1-associated plexiform neurofibromas, with the added advantage of CNS penetration and durable clinical benefit. However, resistance and toxicity remain challenges, and future research should focus on optimizing patient selection and developing combination strategies to further expand its role in NF1-PN management.