Phase 1b/2 Study of TPST-1120 Generates Encouraging Data in First-Line HCC

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Treatment with TPST-1120 demonstrated clinically-meaningful improvements when given in combination with the standard-of-care regimen of atezolizumab (Tecentriq) plus bevacizumab (Avastin) vs atezolizumab and bevacizumab alone for the first-line treatment of patients with unresectable or metastatic hepatocellular carcinoma (HCC).¹

These positive early results come from a global, randomized, phase 1b/2 study (NCT03829436) which evaluated 40 patients in the TPST-1120 who were randomized against 29 evaluable patients in the control arm. In the TPST-1120 triplet arm, 12 patients had an unconfirmed response (30%) vs 5 patients (17.2%) in the control arm, showing a relative improvement in objective response rate (ORR) by 74.4%. With confirmed responses in 7 (17.5%) patients given the TPST-1120 triplet regimen vs 3 (10.3%) given the control, the relative improvement in confirmed ORR was 69.9%.

A total of 47.5% of the patients in the TPST-1120 arm are on treatment compared with 23.3% in the control arm, and 80% of the patients given the combination with TPST-1120 are on study vs 50% in the control arm.

Regarding safety, adding TPST-1120 to the regimen was well-tolerated. Safety data were consistent with the control regimen, and at baseline, the randomized arms were generally well balanced for prognostic factors.

“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 a press 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.

TPST-1120 is a small molecule PPAR⍺ antagonist. In preclinical data, the agent was shown to kill tumor cells directly and target suppressive immune pathways in the tumor microenvironment. In additional extensive non-clinical studies, when TPST-1120 was given as a monotherapy or in combination with other anti-cancer drugs, significant reductions in tumor growth was observed, as well as the stimulation of durable anti-tumor immunity.

Further, a phase 1 trial which evaluated TPST-1120 as monotherapy and in combination with nivolumab (Opdivo) in patients with heavily-pretreated advanced solid tumors showed there to be tumor reduction and biomarker modulation with the agent. As both monotherapy and combination with the PD-1 inhibitor nivolumab, TPST-1120 was well-tolerated.

Now, this phase 1b/2 global randomized study is part of a larger program looking to evaluate. In this study, in particular, TPST-1120 is being administered to patients with unresectable or metastatic HCC in combination with the standard-of-care regimen of atezolizumab and bevacizumab.²

Those enrolled must be 18 years or older and have HCC that has not been previously treated with systemic therapy. Patients are required to have 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.

A total of 70 patients have been enrolled to the 1120 arm and contemporaneous control arm at 25 locations across the globe, including in the United States and Europe.¹ These patients have received either the TPST-1120 combination or the standard-of-care regimen of atezolizumab and bevacizumab. The primary end point of the study is ORR with secondary end points of PFS and OS.

“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,” added Brady.

REFERENCES:

1. Tempest announces positive early results from global randomized phase 1b/2 combination study of TPST-1120 in first-line hepatocellular carcinoma. News release. Tempest Therapeutics. April 28, 2023. Accessed May 2, 2023. https://yhoo.it/3Vmx2vC

2. TPST-1120 as monotherapy and in combination with nivolumab in subjects with advanced cancers. ClinicalTrials.gov. Updated November 3, 2022. Accessed May 2, 2023. https://clinicaltrials.gov/ct2/show/NCT03829436