Tempest Therapeutics' Amezalpat Receives Positive FDA Feedback for Phase 3 HCC Trial
Key Insights
Tempest Therapeutics announced positive feedback from the FDA regarding the Phase 3 trial design for amezalpat (TPST-1120) in first-line hepatocellular carcinoma (search) (HCC).
The FDA agreed on key aspects of the Phase 3 study, including the control arm, study endpoints, amezalpat dose, and statistical plan with an early efficacy analysis.
The Phase 3 trial, expected to begin in Q1 2025, will evaluate amezalpat plus atezolizumab and bevacizumab versus atezolizumab and bevacizumab alone.
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 (search) (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 (search) 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 (search) in the first line setting...[we have] confidence in the potential success of the Phase 3."