On October 11, 2023 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage oncology company developing first-in-class1 therapeutics that combine both targeted and immune-mediated mechanisms, reported new and updated positive results from the planned data analysis of an ongoing global randomized Phase 1b/2 clinical study in which TPST-1120, Tempest’s PPAR⍺ antagonist, shows clinical superiority in multiple study endpoints when combined with atezolizumab and bevacizumab in a randomized comparison to atezolizumab and bevacizumab in the first-line treatment of patients with unresectable or metastatic hepatocellular carcinoma ("HCC") (Press release, Tempest Therapeutics, OCT 11, 2023, View Source [SID1234635859]).
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"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. "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 these 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."
These new data were provided by F. Hoffman La-Roche ("Roche") from a clinical collaboration pursuant to which Roche managed the study operations for this multicenter trial. Tempest retains all product rights to TPST-1120. Data from 40 patients randomized to the TPST-1120 arm and 30 patients randomized to the control arm, with a median follow-up of 9.2 and 9.9 months, respectively, show:
Confirmed objective response rate ("cORR" or "confirmed ORR") of 30% for the TPST-1120 triplet arm versus 13.3% for the atezolizumab + bevacizumab control arm; duration of response ("DoR") has not yet been reached
Hazard ratio ("HR") favors the TPST-1120 arm for key survival endpoints
Progression free survival ("PFS"): median PFS of 7 mo (5.6 mo, 13.8 mo) for TPST-1120 arm versus 4.27 mo (2.8 mo, 7.3 mo) for the control arm; HR of 0.7 favors TPST-1120 arm and is not yet mature
Overall survival ("OS"): median OS not reached for the TPST-1120 arm (10.84 mo, NE) versus 15.1 mo (7.49 mo, NE) for the control arm; HR 0.59 favors TPST-1120 arm and is not yet mature
New biomarker subpopulation findings are consistent with the mechanism of action of TPST-1120
Patients with b-catenin activating mutations (21% in this study (n=7)) showed a cORR of 43% and a disease control rate ("DCR") of 100% in the TPST-1120 arm
Distinct from the control arm, the TPST-1120 arm was consistently active across both PD-L1 positive and PD-L1 negative tumors, with a cORR of 27% in the TPST-1120 arm compared to 7% for the control arm in PD-L1 negative tumors
40% of the patients in the TPST-1120 arm were on treatment (16/40) compared to 16.7% in the atezolizumab + bevacizumab control arm (5/30)
72.5% of the patients on the TPST-1120 arm were on study (29/40), compared to 46.7% on the atezolizumab + bevacizumab control arm (14/30)
TPST-1120 remains well tolerated, with safety data comparable between the two arms
The randomized arms were generally well balanced at baseline
Secondary endpoints include DoR, PFS, and OS, which are not fully mature as of the data cut. In Roche’s IMbrave150 Phase 3 trial, confirmed ORR benefit correlated with overall survival (OS) benefit.2
Enrollment began in fall of 2021 and the cutoff date for these data was April 20, 2023. Tempest expects the data set to be jointly presented by Roche and Tempest at a medical meeting at a later date. ORR was determined by RECIST v1.1, and confirmed responses included at least two scans.
Conference Call & Webcast Information
Tempest will host a webcast conference call today, October 11, 2023 at 8:30am ET.
To join the conference call via phone and participate in the live Q&A session, please pre-register online here to receive a telephone number and unique passcode required to enter the call. The live webcast and audio archive of the presentation may be accessed on the investor section of the Tempest website at View Source The webcast will be available for replay for 30 days.
About the Randomized Clinical Trial
The Phase 1b/2 global randomized HCC study is part of Roche’s Morpheus program and evaluates TPST-1120 in combination with atezolizumab and bevacizumab versus atezolizumab and bevacizumab, the standard of care, in patients with unresectable or metastatic HCC not previously treated with systemic therapy. The trial enrolled 70 patients to the TPST-1120 arm and contemporaneous control arm at approximately 25 sites worldwide, including in the United States, Europe, and Asia, who received either the TPST-1120 combination or atezolizumab and bevacizumab with primary efficacy endpoint of objective response rate, and key secondary endpoints including PFS and OS. Under the terms of the clinical collaboration agreement, Roche is managing the study operations for this global, multicenter trial and Tempest retains all product rights.
About TPST-1120
TPST-1120 is an oral, small molecule, selective PPAR⍺ antagonist wholly-owned by Tempest. Tempest’s data suggest that TPST-1120 treats cancer by targeting tumor cell metabolism directly, as well as by modulating immune suppressive cells and angiogenesis in the tumor microenvironment. In a Phase 1 clinical trial in patients with heavily-pretreated advanced solid tumors, TPST-1120 as monotherapy and in combination with the PD-1 inhibitor nivolumab demonstrated tumor reduction (including according to RECIST criteria), as well as biomarker modulation. TPST-1120 was well-tolerated both as a monotherapy and in combination with nivolumab.
About Hepatocellular Carcinoma
HCC is an aggressive cancer with rising mortality and is projected to become the third leading cause of cancer death by 2030.3 Every year, more than 900,000 people worldwide are diagnosed with HCC.4 Incidence and mortality are highest in East Asia and are increasing in parts of Europe and the US.5 In the US, HCC represents the fastest-rising cause of cancer-related death.3
Nine out of ten cases of HCC are caused by chronic liver disease, which includes chronic hepatitis B and C infection, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcohol-related liver disease (ALD) and cirrhosis resulting from these conditions.6
Even if diagnosed in the early stage, an estimated 70-80% of people with early-stage HCC experience disease recurrence following surgery.7 Early recurrence is associated with poorer prognosis and shorter survival.5,8 Tumor size, number of tumors, and portal vein invasion are associated with an increased risk of recurrence.6