Tempest touts early data for PPAR alpha antagonist in front-line liver cancer

28 Apr 2023
firstwordpharma.com
Clinical ResultPhase 1
Tempest Therapeutics on Friday announced that its experimental PPAR⍺ antagonist TPST-1120 demonstrated "clinically-meaningful improvement in multiple categories" when combined with a standard-of-care regimen in a Phase Ib/II trial of patients with unresectable or metastatic hepatocellular carcinoma (HCC). Company shares gained as much as 28% on the news.
The randomised study is part of Roche's Morpheus programme and evaluates the addition of TPST-1120 to the PD-L1 inhibitorPD-L1 inhibitor Tecentriq (atezolizumab) plus anti-VEGF antibody Avastin (bevacizumab), compared to the combination of Tecentriq and Avastin, in patients with unresectable or metastatic HCC not previously treated with systemic therapy. The two companies entered into a partnership to test the triplet regimen in 2021.
Tempest says that 70 patients have so far been enrolled in the study's 1120 arm and contemporaneous control arm. The analysis looked at data from 40 patients in the TPST-1120 arm against 29 evaluable control group participants. Results for the primary efficacy endpoint of objective response rate (ORR) showed a 74.4% relative improvement for those in the triplet arm versus controls, including a 69.9% relative improvement in confirmed ORR. According to Tempest, both the confirmed and unconfirmed response rates were clinically meaningful. Key secondary endpoints include progression-free survival and overall survival (OS).
The company noted that the number of patients on treatment, as well as on study, "markedly favours" the TPST-1120 arm, at rates of 47.5% and 80%, respectively, compared to 23.3% and 50% for the comparator arm. The addition of TPST-1120 was also well tolerated, with safety data consistent with the control regimen, it added.
"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," commented CEO Stephen Brady, adding "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."
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