Mekinist (trametinib)

In this NF1 cohort, cardiotoxicity occurred in 23% of patients but only one case required trametinib discontinuation. Events occurred within the first year, were usually moderate, and reversible. NT-proBNP remained normal in most cases but may help identify patients needing echocardiography. We recommend continuing echocardiography during the first year, with consideration for less frequent monitoring thereafter based on clinical findings. However, further data are needed for long-term surveillance.

P2, N=40, Completed, Gustave Roussy, Cancer Campus, Grand Paris | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Jan 2026

He was treated with repeat radiation and temozolomide chemotherapy but developed recurrence with disseminated leptomeningeal disease thereafter. Based on these findings, the patient was treated with a MEK inhibitor, trametinib, and achieved durable disease control for 20 months until progression. This case underscores the importance of genomic profiling in RIGs and potential utility of molecularly targeted approaches in this population.

Infants, less than 1 year, with chiasmatic gliomas (ICG) present a major therapeutic challenge due to large tumor size, decreased vision, rapid progression, and poor response to vincristine/carboplatin chemotherapy. We report two infants with BRAF-fused ICG presenting at age 5 months with nystagmus and diencephalic syndrome. Significant tumor progression occurred after only 6 weeks on chemotherapy and showed dramatic response to the addition of trametinib.

P2, N=45, Recruiting, Memorial Sloan Kettering Cancer Center

We retrospectively analyzed data of five adult patients (ages 30-79), four with PAs and one with PA with anaplastic transformation, that were administered trametinib, a MEK1/2 inhibitor...According to RANO 2.0 criteria, three patients achieved partial responses and two had stable disease, with neurological improvement in two cases. Median progression-free survival was 16.65 months, supporting MEK inhibition as an effective treatment strategy in adult PAs.

Solid organoids were more trametinib-sensitive and exhibited higher Wnt-3a levels, suggesting divergent cell compositions and pathway dependencies. Our findings highlight the functional relevance of non-genetic variability in organoid cultures and establish a framework to improve reproducibility and biological insight in PDO-based drug screening.

These studies demonstrate in vitro efficacy for two candidate MPNST therapeutics which could reduce tumor burden and metastasis in NF1 patients.

P1, N=30, Active, not recruiting, Massachusetts General Hospital | Recruiting --> Active, not recruiting | Trial primary completion date: Sep 2025 --> Jul 2026

P2, N=280, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027 | Trial primary completion date: Mar 2026 --> Mar 2027

Gliomas can be devastating for children and their families. In addition to providing a cost-effective option, treatment with D+T allows patients to be managed away from the hospital and so may help alleviate NHS capacity issues.

P2, N=134, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2026 --> Feb 2027 | Trial primary completion date: Mar 2026 --> Feb 2027