In a Phase Ib/II study, Tempest Therapeutics’ investigational PPAR⍺ antagonist—combined with Roche’s Avastin and Tecentriq—showed strong signs of survival benefits in liver cancer patients.
Pictured: Blue upward trendline showing rising stock prices/iStock, Igor Kutyaev
Tempest Therapeutics on Wednesday announced that its investigational PPAR⍺ antagonist TPST-1120 induced significant survival and treatment response improvements in a Phase Ib/II study in patients with unresectable or metastatic hepatocellular carcinoma.
These data excited the market, sending Tempest’s stock skyrocketing nearly 4,000% in trading. The company’s closing price Wednesday was $9.77 after opening at $2.13, according to Seeking Alpha.
Wednesday’s analysis includes more mature clinical data and demonstrates “an even greater benefit than the earlier interim analysis of the TPST-1120 triplet therapy over standard of care alone,” Tempest CEO Stephen Brady said in a statement. The company had posted a previous readout from the study in April 2023, when a substantial proportion of response rate data were still unconfirmed.
With these results, Tempest is now planning to advance TPST-1120 into a pivotal study, Brady said.
TPST-1120’s new data come from a randomized study that combined TPST-1120 with Roche’s Avastin (bevacizumab) and Tecentriq (atezolizumab) and compared this tri-therapy with standard-of-care, which consisted of only Avastin and Tecentriq.
Patients who were treated with the TPST-1120-based combo achieved a confirmed objective response rate (cORR) of 30%, the study’s primary endpoint. This was more than twice the 13.3.% cORR in patients who received the standard-of-care regimen. Duration of response had not yet been reached.
Patient survival was a key secondary measure of the study. After 9.2 months of follow-up, TPST-1120 treatment led to a median progression-free survival (PFS) of seven months versus 4.27 months in 9.9 months of follow-up in control comparators. Overall survival had not yet been reached in the TPST-1120 arm and was 15.1 months in the standard-of-care group.
These yielded hazard ratios of 0.7 for PFS and 0.59 for OS in favor of Tempest’s candidate, though these figures are not yet mature and cannot be assessed for significance, according to the company’s announcement.
In terms of safety, the candidate was generally well tolerated and signals arose at comparable rates between the two treatment arms.
TPST-1120 is an oral small molecule drug candidate that works by blocking the PPARα transcription factor, which helps regulate inflammation and fatty acid oxidation, and is over-expressed in several cancers including hepatocellular carcinoma, cholangiocarcinoma and renal cell carcinoma, according to Tempest’s website.
The Phase Ib/II study is being run by Roche, which is responsible for managing the operations of the trial, under a prior clinical collaboration. Tempest fully owns TPST-1120 but is looking to use this recent readout to advance “discussions with potential partners,” Brady said in a statement.
Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.
