Cotellic (cobimetinib)

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

P1/2, N=314, Active, not recruiting, Hoffmann-La Roche | Trial completion date: Nov 2026 --> Nov 2025

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

Treatments included vemurafenib, interferon, tocilizumab, cladribine, cobimetinib, and cytarabine. Treatment responses varied, with several patients achieving remission or stable disease, while others had progressive or end-stage disease. This study highlights the clinical heterogeneity of ECD and the value of integrating histopathology, molecular profiling, and imaging to guide management and improve outcomes.

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.

P2, N=99, Recruiting, Genentech, Inc. | Trial completion date: Mar 2029 --> May 2030 | Trial primary completion date: Dec 2025 --> Nov 2026

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