Publications by authors named "Meredith A McKean"

Article Synopsis
  • RAF inhibitors have improved treatment for BRAFV600-mutant cancers, but challenges like ERK signaling adaptation and poor brain penetration limit their effectiveness.
  • PF-07799933 is a new, brain-penetrant, selective pan-mutant BRAF inhibitor that shows promising results in preclinical trials by inhibiting dimer signaling and maintaining wild-type ERK signaling.
  • A clinical trial for PF-07799933 demonstrated it was well-tolerated and led to multiple positive responses in patients with treatment-resistant BRAF-mutant tumors, highlighting its potential as an effective therapy combined with MEK inhibitors.
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Purpose: TPST-1120 is a first-in-class oral inhibitor of peroxisome proliferator-activated receptor α (PPARα), a fatty acid ligand-activated transcription factor that regulates genes involved in fatty acid oxidation, angiogenesis, and inflammation, and is a novel target for cancer therapy. TPST-1120 displayed antitumor activity in xenograft models and synergistic tumor reduction in syngeneic tumor models when combined with anti-PD-1 agents.

Experimental Design: This phase I, open-label, dose-escalation study (NCT03829436) evaluated TPST-1120 as monotherapy in patients with advanced solid tumors and in combination with nivolumab in patients with renal cell carcinoma (RCC), cholangiocarcinoma (CCA), or hepatocellular carcinoma.

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Stage III melanoma encompasses a range of disease burdens, including microscopic foci of metastatic melanoma in a sentinel lymph node; bulky, clinically detected lymphadenopathy; and in-transit dermal metastases. After initial surgical management, patients with stage III melanoma at highest risk for recurrence are most likely to benefit from adjuvant therapy. Novel therapies that have improved the disease response rates and long-term survival of patients with advanced or metastatic melanoma have now been evaluated in the adjuvant setting, with the goal of eliminating residual microscopic disease to improve relapse-free and overall survival.

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Locally advanced and metastatic melanoma have historically had poor survival outcomes. Long-term follow-up of both targeted therapies and immune checkpoint inhibitors has confirmed the survival benefit of these agents in stage IV melanoma, and recent studies have now demonstrated relapse-free survival benefits from these targeted and immunotherapeutic agents in the adjuvant setting. Neoadjuvant treatment of locally advanced melanoma, including in-transit disease, is now under investigation.

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