Tempest Therapeutics, Inc. has announced positive feedback from the U.S. Food and Drug Administration (FDA) regarding its end-of-Phase 2 meeting for amezalpat (TPST-1120) in combination with atezolizumab and bevacizumab for the treatment of first-line unresectable or metastatic hepatocellular carcinoma (HCC). This agreement paves the way for a Phase 3 clinical trial, anticipated to commence in the first quarter of 2025.
FDA Agreement on Phase 3 Trial Design
The FDA's feedback encompasses several critical elements of the planned Phase 3 study. These include agreement on the study design, which will utilize atezolizumab and bevacizumab as the standard-of-care control arm. The FDA also concurred with the appropriateness of the current amezalpat dose and schedule for the Phase 3 study. A key aspect of the agreement is the statistical plan, which includes a pre-specified early efficacy analysis. Tempest Therapeutics estimates that this analysis could potentially shorten the time to primary analysis by up to eight months.
Planned Phase 3 Study Details
The Phase 3 study, designated TPST-1120-301, is designed as a global, blinded, 1:1 randomized trial. It will compare amezalpat in combination with atezolizumab and bevacizumab against atezolizumab and bevacizumab alone in patients with unresectable or metastatic HCC receiving first-line treatment. This Phase 3 study closely mirrors the randomized Phase 2 study where a favorable hazard ratio for overall survival was observed.
Amezalpat (TPST-1120) Mechanism of Action
Amezalpat is an oral, small molecule, selective PPARα antagonist. Preclinical and clinical data suggest that amezalpat exerts its anti-cancer effects through direct targeting of tumor cells and by modulating immune suppressive cells and angiogenesis within the tumor microenvironment. In an ongoing global randomized phase 1b/2 study, amezalpat, when combined with atezolizumab and bevacizumab, demonstrated clinical superiority across multiple study endpoints compared to the standard of care (atezolizumab and bevacizumab alone) in first-line patients with advanced HCC. These findings were further supported by positive results from a Phase 1 clinical trial involving patients with heavily pretreated advanced solid tumors.
Sam Whiting, M.D., Ph.D., chief medical officer and head of R&D at Tempest, stated, "Tempest and the FDA are in broad agreement on all major aspects of the proposed pivotal Phase 3 clinical trial for amezalpat in patients with hepatocellular carcinoma in the first line setting...[we have] confidence in the potential success of the Phase 3."
