FDA Approves Phase 3 Trial of Amezalpat in First-Line Liver Cancer
核心洞察
The FDA has approved a "Study May Proceed" letter for a phase 3 trial evaluating amezalpat in combination with atezolizumab and bevacizumab for unresectable or metastatic hepatocellular carcinoma (搜索) (HCC (搜索)).
The trial will compare the amezalpat regimen to the current standard of care (atezolizumab and bevacizumab) as a first-line treatment for advanced HCC (搜索), with the study slated to begin in early 2025.
Amezalpat, an oral small-molecule antagonist targeting PPARα (搜索), has shown potential in earlier phase studies to improve survival in patients with HCC (搜索) by directly targeting tumor cells and modulating the tumor microenvironment.
The FDA has given the green light to a phase 3 clinical trial evaluating amezalpat (formerly TPST-1120) in combination with atezolizumab (Tecentriq) and bevacizumab (Avastin) as a first-line treatment for patients with unresectable or metastatic hepatocellular carcinoma (搜索) (HCC (搜索)). This pivotal trial aims to assess the efficacy of amezalpat in improving outcomes for patients facing this challenging cancer.
The international, double-blind, 1:1 randomized study will compare the amezalpat regimen with a placebo plus the current standard of care (SOC) of atezolizumab and bevacizumab. The trial is anticipated to begin in the first quarter of 2025.
Amezalpat's Mechanism and Prior Clinical Data
Amezalpat is an oral, small-molecule antagonist targeting PPARα (搜索). Preclinical research suggests that amezalpat may combat cancer through multiple mechanisms, including direct action on tumor cells, modulation of immune-suppressive cells, and reduction of angiogenesis within the tumor microenvironment.
Previous phase 1b/2 studies evaluating amezalpat in combination with atezolizumab and bevacizumab for first-line treatment of advanced HCC (搜索) have demonstrated promising clinical advantages across multiple endpoints, including improved overall survival. One such study (NCT03829436) showed a confirmed objective response rate of 30% in the amezalpat arm compared to 13.3% in the control arm. At median follow-ups of 9.2 and 9.9 months, 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.
Trial Design and Objectives
The phase 3 trial will enroll an estimated 740 patients with unresectable or metastatic HCC (搜索). The primary objective of the study is to determine if amezalpat, when added to atezolizumab and bevacizumab, can improve overall survival compared to the standard-of-care treatment alone. Researchers will also assess progression-free survival as a key secondary endpoint. The estimated primary completion date for the trial is March 2028.
"The clinical and regulatory team at Tempest (搜索) 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. "Previously reported positive phase 2 data underscore amezalpat’s potential to improve the survival of patients facing this life-threatening disease."