Mekinist (trametinib)

P1, N=50, Recruiting, University of California, San Francisco | Suspended --> Recruiting

P=N/A, N=82, Completed, Novartis Pharmaceuticals

This regimen is highly clinically accessible and may serve as a second-line treatment option when KRAS G12C-specific inhibitors are unavailable. Its clinical value requires further validation through large-sample prospective studies.

As a result, we found that any possible 2-drug combination of venetoclax, ponatinib, and trametinib was highly synergistic in vitro. Regrettably, none of the synergistic 2-drug combinations appeared sufficiently effective in preventing leukemia outgrowth in our PDX models, which likely requires combinations of >2 drugs. Hence, our results illustrate/signify that straightforward high-throughput combinatorial drug screening in leukemia cell lines is a valid approach to identify synergistic drug combinations that are verifiable in vivo in PDX mouse models without requiring validation in primary patient cells in vitro.

The LiBRA study supports liquid biopsy as a prognostic and monitoring tool in BRAF V600E-mutated NSCLC undergoing targeted therapy.

High-level evidence, including prospective interventional studies, supports exposure-guided dosing for imatinib and sunitinib, demonstrating improved molecular or clinical outcomes when predefined trough concentration targets are achieved. For alectinib, cabozantinib, trametinib, and lenvatinib, consistent exposure-response or exposure-toxicity relationships and pragmatic concentration thresholds support selective implementation, although randomized validation remains limited. For agents such as osimertinib, brigatinib, olaparib, and niraparib, monitoring appears most clinically relevant in toxicity-driven scenarios rather than for efficacy optimization. In contrast, lorlatinib currently lacks a clearly defined therapeutic window, limiting routine applicability...In conclusion, therapeutic drug monitoring and model-informed precision dosing are ready for selective clinical adoption in a subset of oral targeted therapies. Future prospective trials integrating pharmacometric tools with patient-centered outcomes are required to refine exposure targets and expand evidence-based implementation.

Personalized treatment recommendations were made for 13 patients, and 11 received matched therapies: dabrafenib ± trametinib (n = 9), futibatinib (n = 1), or binimetinib (n = 1). These findings demonstrate frequent actionable alterations in ameloblastoma and clinically meaningful responses of targeted therapies. Incorporating precision oncology into standard care may facilitate personalized, less morbid surgery and improved outcomes in these rare tumors.

We report a 59-year-old female non-smoker with stage IV EGFR Leu858Arg-mutated lung adenocarcinoma who sequentially received first-line osimertinib (~9 months), second-line osimertinib plus savolitinib for MET amplification (~20 months), third-line platinum-based chemotherapy with local ablative therapy for oligo-progression, and fourth-line docetaxel. This case illustrates that an acquired BRAF fusion may emerge as a potentially targetable bypass alteration in EGFR-mutated MET-amplified NSCLC after progression on combined EGFR-MET inhibition and that the combination of a first-generation EGFR-TKI and a MEK inhibitor can be associated with prolonged systemic disease control. The findings are hypothesis-generating and support the value of CGP at sequential progression points to guide mechanism-based therapy in oncogene-driven NSCLC.

P1/2, N=40, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting

Reduced-dose dabrafenib and trametinib were initiated with prophylactic naproxen to mitigate the risk of pyrexia. Treatment has been continued for over 6 months with sustained disease stability. This case suggests that an upfront dose-attenuation strategy combined with proactive toxicity management, including pyrexia prophylaxis, may represent a practical approach to maintain treatment continuity and clinical benefit in selected very elderly or frail patients.

Resistance to RET inhibitors can be acquired through RET copy-number gain and secondary mutations as well as NF1 loss-mediated MAPK pathway activation. This mechanism of resistance can be overcome with dual inhibition of RET and downstream RAS/MAPK signaling, demonstrating clinical potential in RET-mutant MTC.

PTPA promotes oncogene-induced senescence (OIS) in MPM. By preventing OIS, heterozygous PTPA loss may contribute to mesothelial transformation and carboplatin resistance.