Tempest Therapeutics, Inc. and Roche have entered into an agreement to advance amezalpat, Tempest's investigational drug, into a Phase 3 clinical trial for first-line treatment of unresectable or metastatic hepatocellular carcinoma (HCC). The study, anticipated to commence in the first quarter of 2025, will evaluate the efficacy of amezalpat in combination with Roche's atezolizumab (Tecentriq®) and bevacizumab against the current standard of care for HCC.
Phase 3 Trial Design and Objectives
The Phase 3 trial is designed as a global, blinded, 1:1 randomized study. It will compare the combination of amezalpat, atezolizumab, and bevacizumab to atezolizumab and bevacizumab alone in patients with unresectable or metastatic HCC receiving first-line treatment. The primary endpoint of the study is overall survival (OS). The FDA has agreed to the Phase 3 study design, the dose of amezalpat, and the statistical plan, which includes a pre-specified early efficacy analysis that could potentially shorten the study's timeline to primary analysis by eight months.
Background and Rationale
The collaboration is an extension of a previous Phase 1b/2 study where the combination of amezalpat, atezolizumab and bevacizumab demonstrated promising results compared to the standard treatment. Updated data from the ongoing Phase 1b/2 trial showed a six-month improvement in median overall survival (OS) for patients treated with the combination therapy. This survival benefit was observed across key subpopulations, including patients with specific gene mutations. These encouraging results prompted the advancement of amezalpat into a pivotal Phase 3 trial.
Amezalpat: Mechanism of Action
Amezalpat (TPST-1120) is an oral, small molecule, selective PPARα antagonist. Preclinical data suggests that amezalpat exerts its anti-cancer effects by directly targeting tumor cells and by modulating immune suppressive cells and angiogenesis within the tumor microenvironment. The Phase 1b/2 study also indicated that the amezalpat combination therapy provided clinical benefit regardless of PD-L1 status and in patients with both immune excluded and immune desert tumors. Patients with a mutation in the beta catenin gene had an increased objective response rate and a longer median OS.
Leadership Perspective
Stephen Brady, president and chief executive officer of Tempest, expressed optimism about the potential of amezalpat to improve first-line liver cancer treatment. "Based on the positive Phase 2 data, I believe this combination therapy holds the potential to significantly improve first-line liver cancer treatment, and we look forward to amezalpat moving into this pivotal Phase 3 study."
Commercial and Development Rights
Under the agreement, Roche will supply atezolizumab globally for the Phase 3 trial. Tempest retains all development and commercial rights to amezalpat.
