FDA Supports Phase 3 Plan for Amezalpat in Hepatocellular Carcinoma

• Positive feedback on the combination of amezalpat (TPST-1120), atezolizumab (Tecentriq), and bevacizumab (Avastin) for the first-line treatment of patients with unresectable or metastatic hepatocellular carcinoma (HCC) were announced.
• These outcomes come from an end-of-phase 2 (EOP2) meeting between the FDA and Tempest Therapeutics, Inc.
• The FDA and the company reached agreements on the phase 3 study design, dosing, and statistical plan.

Encouraging results from the combination of amezalpat, atezolizumab, and bevacizumab for first-line treatment of patients with unresectable or metastatic HCC were reported during the EOP2 meeting with the FDA.¹

During the meeting, there was a consensus on several key aspects of the upcoming phase 3 study evaluating amezalpat. The study design was finalized, including the selection of a standard-of-care (SOC) control arm and the determination of both primary and secondary study end points. The FDA also confirmed the appropriateness of the current amezalpat dose and schedule for the phase 3 trial.

Additionally, they reached an agreement on the statistical plan, which includes a prespecified early efficacy analysis that could potentially shorten the time to the primary analysis by up to 8 months, according to the company's current estimates.

"We are thrilled with the positive outcome of our end-of-phase 2 meeting with the FDA,” said Sam Whiting, MD, PhD, chief medical officer and head of research and development at Tempest, in a press release. “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 in the first line setting.”

3D illustration of liver cancer: © vitanovski - stock.adobe.com

Amezalpat is an oral, small molecule, selective PPAR⍺ antagonist.² An ongoing, global, randomized, 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. Seventy patients were randomized in the study to receive the combination with amezalpat (n = 40) or the control (n = 30), and 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.³

Further, 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.

The upcoming phase 3 study will be a global and blinded trial evaluating treatment with amezalpat plus atezolizumab and bevacizumab compared with atezolizumab and bevacizumab, the SOC, in patients with unresectable or metastatic HCC treated in the first-line setting. Here, patients will be randomized 1:1.¹

Initiation of the phase 3 study is expected in the first quarter of 2025.

“This planned phase 3 study closely mirrors the randomized phase 2 study and the strongly favorable hazard ratio for overall survival observed at top-line analysis of the phase 2, confirmed at the latest survival follow-up, give us confidence in the potential success of the phase 3,” added Whiting in the press release.

REFERENCES:

1. 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 August 16, 2024. https://tinyurl.com/yc8df39h

2. Pipeline. Tempest Therapeutics, Inc. Accessed August 15, 2024. https://www.tempesttx.com/pipeline/

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 August 15, 2024. https://tinyurl.com/msx4nb4c