On September 20, 2021 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company developing potentially first-in-class therapeutics that combine both targeted and immune-mediated mechanisms, reported the first patient has been dosed in the global randomized Phase 1b/2 clinical study evaluating TPST-1120, Tempest’s small molecule PPAR⍺ antagonist, in combination with the standard-of-care regimen of atezolizumab and bevacizumab in the first-line treatment of patients with advanced or metastatic hepatocellular carcinoma ("HCC") (Press release, Tempest Therapeutics, SEP 20, 2021, View Source [SID1234588005]). The trial is being conducted under a clinical collaboration with F. Hoffman La-Roche ("Roche").
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"The initiation of this randomized TPST-1120 study in collaboration with Roche marks significant progress in the advancement of the Tempest clinical pipeline," said Sam Whiting, MD, Ph.D., chief medical officer of Tempest. "We continue to be excited about TPST-1120’s mechanism of action and are encouraged by its safety profile and early signals of clinical benefit seen in both monotherapy and combination studies. The Tempest team looks forward to further evaluation of TPST-1120 in this randomized combination in the first-line treatment of patients with HCC."
"Atezolizumab plus bevacizumab is the standard-of-care for most patients with HCC, but new combinations are needed to further improve patient outcomes," said Mark Yarchoan, M.D., Assistant Professor of Medicine at Johns Hopkins University School of Medicine and Co-Director of the Liver Cancer Multidisciplinary Clinic. "In preclinical models, TPST-1120’s mechanism of action is complementary with the immune mechanism of atezolizumab and the anti-VEGF mechanism of bevacizumab. Additionally, activation of the B-catenin pathway, which is quite common in HCC, has been associated with direct benefit from targeting the metabolic pathway inhibited by TPST-1120. For these reasons, the triplet regimen of the three drugs together is particularly interesting for evaluation in patients with HCC."
The Phase 1b/2 global randomized study will evaluate TPST-1120 in combination with the standard-of-care regimen of atezolizumab and bevacizumab in patients with advanced or metastatic HCC not previously treated with systemic therapy. At least 40 and up to 60 patients will receive the TPST-1120 combination at approximately 25 sites worldwide including the United States, Asia, and Europe, and will be compared to the standard-of-care atezolizumab and bevacizumab regimen with primary objectives of anti-tumor activity and safety. Under the terms of the collaboration agreement, Roche will manage the study operations for this global, multicenter trial. Tempest retains global development and commercialization rights to TPST-1120.
About TPST-1120
TPST-1120 is an oral, small molecule, selective PPAR⍺ antagonist. Tempest’s preclinical data suggest that TPST-1120 can kill tumor cells directly and target suppressive immune pathways in the tumor microenvironment. Both types of targeted cells can be dependent on fatty acid metabolism, which is regulated by the PPAR⍺ transcription factor. In extensive non-clinical studies, TPST-1120 as a monotherapy or in combination with other anti-cancer drugs resulted in significant reductions in tumor growth and stimulation of durable anti-tumor immunity. In an ongoing Phase 1 clinical trial, TPST-1120 has been well-tolerated by patients with advanced cancers as monotherapy and in combination with the PD-1 inhibitor nivolumab, and has demonstrated tumor reduction (including according to RECIST criteria), as well as biomarker modulation.
About Hepatocellular Carcinoma
HCC is an aggressive cancer with limited treatment options and is a major cause of cancer deaths worldwide. Every year, more than 815,000 people worldwide are diagnosed with HCC. In the US, the number of liver cancer cases have more than tripled since 1980 and HCC represents the fastest-rising cause of cancer-related death, while in Europe, liver cancer is also on the rise. HCC develops predominantly in people with cirrhosis due to chronic hepatitis (B or C) or alcohol consumption, and typically presents at an advanced stage. The prognosis for unresectable HCC remains poor, with few systemic therapeutic options and a 1-year survival rate of less than 50% following diagnosis.