Tempest Reveals Amezalpat (TPST-1120) Shows Six-Month Survival Boost in First-Line HCC Study

Tempest Therapeutics, Inc. has reported promising new data from its ongoing global randomized Phase 1b/2 clinical trial involving TPST-1120 (amezalpat), an oral PPAR⍺ antagonist. In combination with atezolizumab and bevacizumab, amezalpat has shown a six-month improvement in median overall survival (OS) compared to the conventional treatment of atezolizumab and bevacizumab alone in patients with unresectable or metastatic hepatocellular carcinoma (HCC). The median OS for the amezalpat arm reached 21 months, compared to 15 months in the control arm.

Stephen Brady, the president and CEO of Tempest, highlighted the significance of these findings, which come after an additional 10 months of follow-up since the last data analysis. The results showed a robust hazard ratio (HR) of 0.65 favoring the amezalpat combination, maintaining stability from an earlier HR of 0.59. Additionally, half of the patients in the amezalpat arm are still in survival follow-up, further underlining the treatment's efficacy.

The study, which included 70 patients, divided participants into two groups: 40 received the amezalpat combination, and 30 were given the standard treatment. The amezalpat arm demonstrated a six-month advantage in median OS, with 20 of 40 patients continuing in survival follow-up, compared to 9 of 30 in the control group. Safety profiles were manageable and consistent with prior Phase 1 data.

Earlier top-line data analysis on April 20, 2023, revealed a confirmed objective response rate (cORR) of 30% for the amezalpat arm, compared to 13.3% for the control group. The findings also indicated that amezalpat was effective across various biomarker subpopulations, including patients with b-catenin activating mutations, who showed a 43% cORR and a 100% disease control rate (DCR).

Amezalpat has shown efficacy in both PD-L1 positive and PD-L1 negative tumors, achieving a cORR of 27% in PD-L1 negative tumors, compared to 7% for the control arm. The study's randomized arms were balanced at baseline, and confirmed responses were determined by RECIST v1.1 criteria, based on at least two scans.

The trial is part of Roche’s Morpheus program and evaluates amezalpat in combination with atezolizumab and bevacizumab versus the standard of care (atezolizumab and bevacizumab alone) in patients with unresectable or metastatic HCC who have not previously been treated with systemic therapy. Conducted at approximately 25 sites worldwide, including the US, Europe, and Asia, the primary efficacy endpoint was the confirmed objective response rate, with progression-free survival (PFS) and OS as key secondary endpoints. Roche manages the study operations, but Tempest retains all product rights to amezalpat.

Amezalpat aims to treat cancer by directly targeting tumor cells and modulating immune-suppressive cells and angiogenesis within the tumor microenvironment. Positive results from this global randomized phase 1b/2 study have confirmed its clinical superiority across multiple study endpoints compared to the standard of care.

HCC is a particularly aggressive cancer, with rising mortality rates and a projection to become the third leading cause of cancer death by 2030. More than 900,000 people worldwide are diagnosed with HCC annually, with the highest incidence and mortality rates in East Asia. Chronic liver disease is a primary cause of HCC, encompassing conditions like hepatitis B and C, NAFLD, NASH, ALD, and cirrhosis. Even in early stages, HCC has a high recurrence rate following surgery, associated with poorer prognosis and survival.

Tempest Therapeutics, headquartered in Brisbane, California, is a clinical-stage biotechnology company developing small molecule therapeutics aimed at treating a wide range of tumors through tumor-targeted and immune-mediated mechanisms.