P1, N=26, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Nov 2025 --> Nov 2026

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