TPST-1120 is displaying potential in combatting hepatocellular carcinoma, the fastest-rising cause of cancer-related death in the United States.
Patients with unresectable or metastatic hepatocellular carcinoma (HCC) experienced clinically meaningful improvements during a study for a new treatment, results that have been described as “promising” as that tumor type is seeing rising mortality rates in the United States.
When combined with the standard-of-care treatment of Tecentriq (atezolizumab) and Avastin (bevacizumab) in first-line treatment, TPST-1120 – an oral, small molecule, selective PPAR⍺ antagonist – showed a confirmed objective response rate of 17.5%, or seven out of 40 participants. That was 69.9% higher than the 10.3% response rate (three out of 29) among patients treated with just Tecentriq and Avastin, according to a news release from clinical-stage oncology company Tempest Therapeutics, Inc.
The global randomized Phase 1b/2 clinical study also showed an unconfirmed response (meaning patients saw some improvement but more testing is required) among 30% (12 out of 40) of patients who received TPST-1120, 74.4% high than the 17.2% (five out of 29) of patients who were not treated with TPST-1120, Tempest, the makers of TPST-1120, announced on April 28.
“These randomized data in first-line HCC are exciting and support the promise of TPST-1120 as an active small molecule for patients,” said Stephen Brady, chief executive officer of Tempest, in the news release. “HCC is a common and aggressive cancer where significant unmet need remains to improve care in the first line and beyond. We believe the improvements shown in the TSPT-1120 arm validate the hypothesis of targeting HCC with TPST-1120, as well as the mechanistic basis for combination with both a checkpoint inhibitor and VEGF inhibitor. We look forward to receiving more data this year, including with respect to potential biomarkers, and to the potential next steps of this program in HCC and other cancers of interest.”
HCC, Tempest reported, is projected to become the third leading cause of cancer-related death by 2030. More than 900,000 people are diagnosed each year, with the highest incidence and mortality in East Asia and numbers climbing in Europe and the United States. It’s the fastest-rising cause of cancer-related death in America, according to Tempest.
“HCC is one of the few tumor types with increasing mortality in the United States,” Dr. Mark Yarchoan, associate professor of medical oncology at Johns Hopkins School of Medicine, said in the Tempest announcement. “(Tecentriq plus Avastin) is the current preferred frontline therapy, and the addition of TPST-1120 appears to be active and well tolerated. Response rates in HCC can vary significantly across studies, and therefore the use of a randomized, controlled study design instead of a historical control is a strength of this study. The numerically higher response rate and proportion of patients on study with the addition of TPST-1120 is promising. I believe that this is an active agent and I look forward to further clinical development of TPST-1120.”
Preclinical data suggest that TPST-1120 “can kill tumor cells directly and target suppressive immune pathways in the tumor microenvironment,” according to the news release. “Both types of targeted cells can be dependent on fatty acid metabolism, which is regulated by the PPAR⍺ transcription factor.”
The addition of TPST-1120 to the current standard treatment “was well-tolerated, with safety data consistent with the control regimen,” Tempest reported.
The study, which was conducted in clinical collaboration with pharmaceutical company F. Hoffman La-Roche and part of Roche’s Morpheus program, had secondary endpoints including duration of response, progression-free survival (time from treatment until disease worsens) and overall survival (time from treatment until death), which Tempest says will be potentially available later in 2023 or in 2024, with the full data set expected to be presented at an upcoming medical meeting.
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