On April 4, 2024 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage biotechnology company developing first-in-classi targeted and immune-mediated therapeutics to fight cancer, reported that Cancer Research Communications published positive clinical data from the dose-escalation Phase 1 trial of TPST-1120 in an article titled "First-in-Human Phase I Trial of TPST-1120, an inhibitor of PPARα, as Monotherapy or in Combination with Nivolumab, in Patients with Advanced Solid Tumors (Press release, Tempest Therapeutics, APR 4, 2024, View Source [SID1234641791])." The data showed that TPST-1120 demonstrated clinical activity, including tumor shrinkage, even in PD-1 inhibitor refractory and immune compromised cancers, and was well tolerated both as monotherapy and in combination with nivolumab. These earlier Phase 1 data complement the positive Phase 1b/2 data reported in October 2023 from a global randomized study of TPST-1120 in combination with atezolizumab and bevacizumab in first-line patients with advanced HCC, which showed clinical superiority of the TPST-1120 arm across multiple study endpoints and relevant biomarker-defined patient subpopulations.
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"In this Phase 1 study of TPST-1120, we saw the first evidence of anti-tumor activity in multiple cancer types, affirming our belief that PPARα inhibition is an exciting and novel approach for cancer treatment," said Sam Whiting, M.D., Ph.D., chief medical officer and head of R&D at Tempest. "These early-phase data are supported by the positive top line results of the ongoing randomized Phase 1b/2 trial in first-line HCC. We believe there is tremendous potential for TPST-1120 to make a meaningful impact for patients and we look forward to providing updated data this year."
About the TPST-1120 Phase 1 Study
In this first-in-human Phase 1 study, 35 patients were treated with escalating doses of TPST-1120 either as monotherapy (20 patients) or in combination with the anti-PD-1 therapy, nivolumab (15 patients). TPST-1120 was well-tolerated as monotherapy and in combination, with a maximum tolerated dose not identified and predominantly low-grade toxicity. Notwithstanding the late-line stage of these patients and difficult to treat tumor types, clinical benefit was observed as both a monotherapy and combination.2 In monotherapy, a best response of stable disease (SD) was observed in 53% (10/19) of evaluable patients, with 5 of those patients staying on treatment for more than 5 months. Tumor shrinkage of target lesions on treatment occurred in 21% (4 patients) and a best response of no target lesion growth was seen in 3 additional patients.
In the combination therapy cohorts, including patients with heavily pretreated cholangiocarcinoma (CCA), hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC), the objective response rate (ORR) was 23% (3/13, all partial responses, or PRs) across all dose levels and 30% (3/10) at the two highest dose levels of TPST-1120, suggesting dose-responsive anti-cancer activity. These responses included a 50% ORR in patients with RCC (2/4 evaluable) who had previously progressed on anti-PD-1 therapy, and one patient with heavily pre-treated CCA. Analysis of whole blood specimens revealed changes in expression of PPARα-associated immune genes that were related to TPST-1120 dose levels. Some of these changes were only observed in patients who had partial responses, linking TPST-1120 biological activity to clinical outcome.
About TPST-1120
TPST-1120 is an oral, small molecule, selective PPAR⍺ antagonist. Tempest’s data suggest that TPST-1120 treats cancer by targeting tumor cells directly and by modulating immune suppressive cells and angiogenesis in the tumor microenvironment. In an ongoing global randomized phase 1b/2 study of TPST-1120 in combination with atezolizumab and bevacizumab in first-line patients with advanced HCC, the TPST-1120 arm showed clinical superiority across multiple study endpoints when compared to atezolizumab and bevacizumab alone, the standard of care. These randomized data were supported by positive results observed in the Phase 1 clinical trial in patients with heavily pretreated advanced solid tumors. TPST-1120 is wholly-owned by Tempest.