FDA Fast Tracks Amezalpat for HCC Treatment
Amezalpat received fast track designation from the FDA for the treatment of patients with hepatocellular carcinoma.
- The FDA granted fast track designation to amezalpat (TPST-1120) for the potential treatment of patients with hepatocellular carcinoma (HCC).
- Amezalpat is an oral, small molecule, selective PPAR⍺ antagonist.
- Data from the phase 1b/2 MORPHEUS-LIVER trial (NCT04524871) support this designation.
The FDA has granted amezalpat, a small molecule, oral, selective PPAR⍺ antagonist, fast track designation for the treatment of patients with HCC.1
Findings from the ongoing, phase 1b/2 MORPHEUS-LIVER trial, which were reported in June 2024, support this designation. At a data cutoff date of February 14, 2024, the median overall survival (OS) was 21 months for those treated with the combination of amezalpat, atezolizumab (Tecentriq), and bevacizumab (Avastin; n = 30) vs 15 months for those given atezolizumab plus bevacizumab alone (n = 30; HR, 0.65).2 Additionally, 20 patients treated with the amezalpat combination remained in survival follow-up at the time of analysis compared with 9 patients in the control arm.
In the experimental arm, previous topline data reported in 2023 showed that the confirmed overall response rate (ORR) was 30% compared with 13.3% in the control arm.
Microscopic, photorealistic image of liver tumor cells - Generated with Adobe Firefly
“We are thrilled to receive fast track designation from the FDA,” said Sam Whiting, MD, PhD, chief medical officer and head of research and development of Tempest Therapeutics, in a press release.1 “This designation, following the orphan drug designation granted last month, reinforces the promise of amezalpat as a potential treatment option for patients affected by HCC. We look forward to working closely with the FDA and foreign regulatory agencies to develop amezalpat with the goal of bringing this promising therapy to patients.”
This marks the second regulatory designation granted to amezalpat, following its orphan drug designation from the FDA which was granted in January 2025.
About the MORPHEUS-LIVER Trial
The open-label, multicenter, randomized, umbrella study MORPHEUS-LIVER is a phase 1b/2 trial evaluating immunotherapy-based combinations for the treatment of patients with advanced liver cancer.3 Patients aged 18 years and older with histologically, cytologically, or clinically confirmed locally advanced or metastatic and/or unresectable HCC that is not amenable to curative surgical and/or locoregional therapies and not previously treated with systemic therapy are eligible for enrollment in the study.
Enrollment is also open to patients with a Child-Pugh class A score, a life expectancy of at least 3 months, and an ECOG performance status of 0 or 1. Patients must also have measurable disease per RECIST 1.1 criteria and adequate hematologic and end-organ function in stages 1 and 2 of the trial.
In stage 1, several novel agents are being evaluated with the atezolizumab-plus-bevacizumab backbone. These include tiragolumab (MTIG7192A), tocilizumab (Actema), amezalpat, ADG126, and NKT2152. In addition, tobemstomig is being examined when given in combination with bevacizumab.
Those enrolled in the amezalpat arm are receiving amezalpat at a dose of 1200 mg per day on days 1 to 21 in combination with 1200 mg of atezolizumab on day 1 and 15 mg/kg of bevacizumab on day 1 of each 21-day cycle. Patients in the control arm are receiving the combination of atezolizumab plus bevacizumab following the same dosing schedule.
Patients will continue treatment in both arms until unacceptable toxicity or loss of clinical benefit. Further, patients who discontinue treatment during stage 1 may be eligible to receive a different combination in stage 2.
The primary end point of the study is ORR, and secondary end points consist of progression-free survival, OS, duration of response, disease control rate, and safety.
REFERENCES
Tempest granted fast track designation from the U.S. Food and Drug Administration for amezalpat to treat patients with hepatocellular carcinoma. News release. Tempest Therapeutics. February 10, 2025. Accessed February 10, 2025. https://tinyurl.com/ypyttrbr
Tempest unveils new survival data for amezalpat (TPST-1120) in randomized first-line HCC study demonstrating a six-month improvement over control arm. News release. Tempest Therapeutics. June 20, 2024. Accessed February 10, 2025. https://tinyurl.com/55xs3ut5
A study evaluating the efficacy and safety of multiple immunotherapy-based treatment combinations in patients with advanced liver cancers (MORPHEUS-LIVER). ClinicalTrials.gov. Updated January 13, 2025. Accessed February 10, 2025. https://clinicaltrials.gov/study/NCT04524871
