TPST-1120 Triplet Demonstrates Clinical Benefit in First-Line HCC

Liver cancer, Hepatocellular Carcinoma (HCC), conditions, causes and treatment. 3d illustration : © Crystal light - stock.adobe.com

TPST-1120, a PPAR⍺ antagonist, combined with atezolizumab and bevacizumab demonstrated superiority across multiple end points vs atezolizumab (Tecentriq) and bevacizumab (Avastin) for the first-line treatment of patients with unresectable or metastatic hepatocellular carcinoma (HCC), according to results from the planned data analysis of an ongoing global, randomized, phase 1b/2 study (NCT03829436).1

A total of 40 patients were randomized in the study to receive the combination with TPST-1120, and 30 patients were randomized to the control arm. At a median follow-ups of 9.2 and 9.9 months, respectively, the confirmed objective response rate (ORR) in the TPST-1120 arm was 30% vs 13.3% in the control arm. The duration of response (DoR) has not yet been reached.

Currently, the hazard ratio (HR) favors the TPST-1120 arm for key survival end points. As s as for progression-free survival (PFS), the median PFS in the TPST-1120 arm is 7 months vs 4.27 months in the control arm, and median overall survival (OS) is not reached in the TPST-1120 arm vs 15.1 months in the control arm.

“This comprehensive analysis of more mature clinical data shows an even greater benefit than the earlier interim analysis of the TPST-1120 triplet therapy over standard of care alone, both for the entire study population and in subpopulations of patients, the latter of which was predicted by TPST-1120’s proposed mechanism of action,” said Stephen Brady, president and chief executive officer of Tempest Therapeutics, TPST-1120’s manufacturer, in a press release.

Additional findings from the newly reported biomarker subpopulation showed that results remain consistent with the mechanism of action of TPST-1120. In the study, 7 patients (21%) have b-catenin activating mutations and showed a confirmed ORR of 43% and a disease control rate (DCR) of 100% in the TPST-1120 arm. For both PD-L1-positive and -negative tumors, TPST-1120 arm was consistently active with a confirmed ORR of 27% among patients treated with the TPST-1120 triplet vs 7% for the control arm.

In the TPST-1120 arm, 40% (n = 16) of the patients were on treatment vs 16.7% (n = 5) in the atezolizumab with bevacizumab control arm. A total of 72.5% of patients on the TPST-1120 arm were on study (n = 29) while 46.7% were on the atezolizumab with bevacizumab control arm (n = 14).

Treatment with TPST-1120 remains well-tolerated and the safety data are comparable between the 2 arms. The randomized arms were generally well balanced at baseline.

For the secondary end points of DoR, PFS, and OS, data were not fully mature at this cutoff date.

“First-line HCC remains an indication with substantial opportunity to improve patient outcomes and, based upon these data, we are excited about the opportunity to move TPST-1120 into a pivotal study. Given this new data and the phase 1 evidence of activity beyond HCC, we look forward to advancing discussions with potential partners who share our vision for TPST-1120,” added Brady, in a press release.¹

Enrollment in the trial began fall of 2021 with the data cutoff date for these data set for April 20, 2023. The phase 1b/2 study is assessing TPST-1120 in combination with atezolizumab and bevacizumab vs the standard of care of atezolizumab and bevacizumab for the treatment of patients with unresectable or metastatic HCC not previously treated with systemic therapy.²

Those enrolled in the study are patients aged 18 years or older with HCC that has not been previously treated with systemic therapy, an ECOG performance status of 0-1 at the time of enrollment, progressive disease or previously untreated tumors for which no standard therapy exists or who are treatment-naïve at the time of study entry, and have 1 or more measurable lesions according to RECIST v1.1. Seventy patients were enrolled across arms at approximately 25 sites globally, including in the United States, Europe, and Asia.

The primary end point being evaluated is ORR, with key secondary end points of PFS and OS.

Further results are expected to be presented at a medical meeting at a later date.¹

REFERENCES:

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 October 11, 2023. https://tinyurl.com/msx4nb4c

TPST-1120 as monotherapy and in combination with nivolumab in subjects with advanced cancers. ClinicalTrials.gov. Updated July 3, 2023. Accessed October 11, 2023. https://clinicaltrials.gov/ct2/show/NCT03829436