Tempest and Roche Partner to Advance Amezalpat Therapy for First-Line Hepatocellular Carcinoma Trial

On October 10, 2024, Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage biotechnology company dedicated to developing targeted and immune-mediated therapies for cancer, announced a significant collaboration with Roche. This partnership aims to progress the combination treatment of amezalpat (TPST-1120) with atezolizumab (Tecentriq®) and bevacizumab into a pivotal Phase 3 trial for the initial treatment of unresectable or metastatic hepatocellular carcinoma (HCC), a form of liver cancer that currently has limited treatment options.

Under the terms of the agreement, Roche will provide atezolizumab on a global scale, while Tempest will lead and sponsor the pivotal study. This collaboration expands on an existing clinical partnership where the combination therapy was evaluated in first-line HCC patients. Tempest retains all commercial and development rights to amezalpat.

Stephen Brady, president and chief executive officer of Tempest, expressed enthusiasm about the agreement, highlighting the joint commitment of both companies to pioneering cancer treatments. He emphasized the potential of the combination therapy to improve first-line treatment outcomes for liver cancer patients based on promising Phase 2 data.

In June, Tempest presented updated positive survival data from an ongoing global randomized Phase 1b/2 clinical study. The findings revealed a six-month improvement in median overall survival (OS) for patients treated with the combination therapy compared to those who received only atezolizumab and bevacizumab. The survival benefit was consistent across key subpopulations. Previous data had shown that the combination therapy offered clinical benefits regardless of PD-L1 status and was effective in patients with immune excluded and immune desert tumors. Additionally, patients with a mutation in the beta-catenin gene showed an increased objective response rate and a longer median OS, supported by amezalpat’s mechanism of action.

In August, Tempest held an end-of-phase 2 meeting with the FDA, achieving broad agreement on the Phase 3 study design, including the amezalpat dose schedule and primary endpoint of OS, reflecting the positive Phase 2 results. The FDA also approved the statistical plan, which includes a pre-specified early efficacy analysis that could potentially shorten the time to the primary analysis by eight months.

The planned Phase 3 study is designed as a global, blinded, 1:1 randomized trial comparing the combination of amezalpat with atezolizumab and bevacizumab to the current standard of care (atezolizumab and bevacizumab) in first-line HCC patients. The study is set to commence in the first quarter of 2025, following FDA agreement on the study design, dose of amezalpat, and statistical plan.

Amezalpat is an oral, small molecule, selective PPAR⍺ antagonist. Studies suggest that amezalpat combats cancer by directly targeting tumor cells and modulating immune suppressive cells and angiogenesis within the tumor environment. This mechanism was observed in an ongoing global randomized Phase 1b/2 study where the combination therapy demonstrated clinical superiority in various endpoints, including overall survival, compared to the standard of care.

Tempest Therapeutics is a clinical-stage biotechnology company focused on advancing a diverse portfolio of small molecule candidates with tumor-targeted and immune-mediated mechanisms, aiming to treat a broad spectrum of tumors. The company's innovative programs range from early research to advanced-stage investigations. Headquartered in Brisbane, California, Tempest continues to push the boundaries of cancer treatment through its novel therapeutic approaches.