TPST-1120, a novel oral PPAR⍺ inhibitor, has shown promising results in treating cancers that are resistant to PD-1 inhibitors and those with weakened immune systems. Following encouraging randomized study outcomes, Tempest Therapeutics, a clinical-stage biotech firm, is progressing TPST-1120 to a pivotal Phase 3 trial for hepatocellular carcinoma (HCC). The positive clinical findings from the Phase 1 trial of TPST-1120 were published in Cancer Research Communications, highlighting the drug's effectiveness as a standalone treatment or in combination with nivolumab. The drug was found to be well-tolerated and showed potential in shrinking tumors in patients with advanced solid tumors, including those who had not responded to PD-1 inhibitors.
Dr. Sam Whiting, Tempest's chief medical officer, noted the significance of the Phase 1 study, which exhibited anti-tumor activity across various cancer types, reinforcing the belief in PPARα inhibition as a groundbreaking strategy for cancer treatment. The study involved 35 patients, with 20 receiving TPST-1120 as a monotherapy and 15 in combination with nivolumab. The drug demonstrated a favorable safety profile, with a majority of the observed toxicities being low-grade.
Notably, stable disease was observed in over half of the patients treated with monotherapy, and tumor shrinkage was seen in 21% of them. In combination with nivolumab, TPST-1120 showed an objective response rate of 23% across all dosage levels and 30% at the highest two dosage levels, indicating a potential dose-dependent effect. The drug's impact on PPARα-associated immune gene expression in whole blood specimens was also analyzed, with changes correlating to clinical outcomes in patients with partial responses.
TPST-1120 is a small molecule developed to target cancer cells directly and to modulate the tumor microenvironment by affecting immune suppressive cells and angiogenesis. In an ongoing global Phase 1b/2 study combining TPST-1120 with atezolizumab and bevacizumab for first-line HCC patients, the drug demonstrated superiority over the standard treatment in multiple study endpoints. Tempest Therapeutics, headquartered in Brisbane, California, is advancing a diverse pipeline of small molecule therapies with tumor-targeted and immune-mediated mechanisms. The company's programs are in various stages of development, from early research to late-stage clinical trials.
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