FDA OKs Study of Amezalpat in Frontline Liver Cancer

• The FDA has approved a “Study May Proceed” letter to evaluate amezalpat (formerly TPST-1120) with atezolizumab (Tecentriq) and bevacizumab (Avastin) in a phase 3 trial for patients with unresectable or metastatic hepatocellular carcinoma (HCC).
• This trial will compare the amezalpat regimen with a placebo plus the current standard of care (SOC) of atezolizumab and bevacizumab as a first-line treatment for advanced HCC.
• The trial is set to begin in early 2025.

The FDA has issued a “Study May Proceed” letter for evaluating amezalpat in combination with atezolizumab and bevacizumab as a first-line option for patients with unresectable or metastatic HCC in a pivotal phase 3 randomized trial.¹

The upcoming phase 3 trial is an international, double-blind, 1:1 randomized study that will compare amezalpat combined with atezolizumab and bevacizumab to a placebo plus atezolizumab and bevacizumab, the current SOC, for the initial treatment of patients with unresectable or metastatic HCC.

In August 2024, the FDA approved the study design, dosage of amezalpat, and statistical plan, which includes a prespecified efficacy analysis that could expedite the primary analysis.² Preparations are underway to initiate the phase 3 trial in the first quarter of 2025.

3D illustration of human liver: © PIC4U - stock.adobe.com

The clinical and regulatory team at Tempest are thrilled to receive this notice from FDA with respect to the planned pivotal phase 3 trial to evaluate amezalpat as a potential treatment for first-line liver cancer,” said Sam Whiting MD, PhD, chief medical officer and head of research and development of Tempest, in a press release.¹ “Previously reported positive phase 2 data underscore amezalpat’s potential to improve the survival of patients facing this life-threatening disease, and our team is dedicated to advancing the program and bringing amezalpat to patients.”

About Amezalpat

Amezalpat is an oral, small-molecule antagonist targeting PPAR⍺. Research has shown that the agent may combat cancer by acting directly on tumor cells, as well as by modulating immune-suppressive cells and reducing angiogenesis within the tumor environment.

An ongoing, global, phase 1b/2 randomized study (NCT06680258) evaluating amezalpat in combination with atezolizumab and bevacizumab for first-line treatment of advanced HCC previously demonstrated clinical advantages across multiple end points, including improved overall survival in both the broader patient population and key subgroups vs atezolizumab and bevacizumab alone.

These findings are further supported by positive results from a phase 1b/2 study (NCT03829436) previously showed that the combination of amezalpat with atezolizumab and bevacizumab in the first-line for patients with advanced HCC demonstrated clinical superiority across multiple study end points vs the SOC.³ A total of 70 patients were randomly assigned to receive the combination with amezalpat (n = 40) or the control (n = 30). At median follow-ups of 9.2 and 9.9 months, respectively, the confirmed objective response rate in the amezalpat arm was 30% vs 13.3% in the control arm.

The amezalpat arm was favored regarding hazard ratio for key survival end points. The median progression-free survival in the amezalpat arm was 7 months compared with 4.27 months in the control arm, and median overall survival was not yet reached in the amezalpat arm vs 15.1 months in the control arm.

REFERENCES:

1. Tempest receives FDA study may proceed for pivotal phase 3 trial of amezalpat combination therapy for the treatment of first-line hepatocellular carcinoma. News release. Tempest Therapeutics, Inc. November 12, 2024. Accessed November 13, 2024. https://tinyurl.com/mwhvfph6

2. Tempest announces successful end-of-phase 2 meeting with FDA for amezalpat (TPST-1120) to treat first-line hepatocellular carcinoma. News release. Tempest Therapeutics, Inc. August 15, 2024. Accessed November 13, 2024. https://tinyurl.com/yc8df39h

3. Tempest releases new data demonstrating superiority of TPST-1120 arm across multiple study endpoints in randomized first-line HCC study. News release. Tempest Therapeutics, Inc. Updated October 11, 2023. Accessed November 12, 2024. https://tinyurl.com/msx4nb4c