Publications by authors named "T Freshwater"

Immuno-oncology (IO) is a growing strategy in cancer treatment. Oncolytic viruses (OVs) can selectively infect cancer cells and lead to direct and/or immune-dependent tumor lysis. This approach represents an opportunity to potentiate the efficacy of immune checkpoint inhibitors (ICI), such as pembrolizumab.

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Selumetinib is clinically used for pediatric patients with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas. Until recently, selumetinib had to be taken twice daily, after 2 hours of fasting and followed by 1 hour of fasting, which could be inconvenient. This population analysis evaluated the effect of low- and high-fat meals on the pharmacokinetic (PK) parameters of selumetinib and its active metabolite N-desmethyl selumetinib.

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Article Synopsis
  • MEK inhibitors show potential for immune modulation and may work well with PD-1 inhibitors, leading to a study of selumetinib (a MEK inhibitor) combined with pembrolizumab (an anti-PD-1 antibody) in patients with advanced solid tumors.
  • In this phase 1b trial, 32 patients received a specific schedule of pembrolizumab and selumetinib, with toxicity and safety being primary concerns; dose adjustments were made based on the side effects experienced.
  • While the study did not reach its target for dose-limiting toxicities and found no new safety concerns, the combination treatment resulted in limited tumor response, leading to the decision to stop the trial early due to insufficient efficacy
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C-X-C motif chemokine receptor 2 (CXCR2) has a role in tumor progression, lineage plasticity, and reduction of immune checkpoint inhibitor efficacy. Preclinical evidence suggests potential benefit of CXCR2 inhibition in multiple solid tumors. In this phase 2 study (NCT03473925), adults with previously treated advanced or metastatic castration-resistant prostate cancer (CRPC), microsatellite-stable colorectal cancer (MSS CRC), or non-small-cell lung cancer (NSCLC) were randomized 1:1 to the CXCR2 antagonist navarixin 30 or 100 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks up to 35 cycles.

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