TPST-1120 Combo Yields Positive Activity in Hepatocellular Carcinoma

In an international randomized phase 1b/2 trial (NCT04524871), investigators are assessing TPST-1120 in combination with atezolizumab and bevacizumab compared with atezolizumab plus bevacizumab in those with unresectable or metastatic HCC who have not received any prior systemic therapy.

Investigators reported positive findings when combining the investigational PPAR⍺ antagonist TPST-1120 with atezolizumab (Tecentriq) and bevacizumab (Avastin) as a frontline treatment for patients with hepatocellular carcinoma (HCC), according to a press release on results from a planned data analysis of a phase 1b/2 trial (NCT04524871).

As of a data cutoff of April 20, 2023, the TPST-1120 triplet produced a confirmed objective response rate (ORR) of 30.0% compared with 13.3% with control treatment consisting of atezolizumab plus bevacizumab. Investigators highlighted that duration of response (DOR) had not been reached at the time of the analysis.

The median progression-free survival (PFS) in the TPST-1120 triplet and control treatment arms, respectively, was 7.0 months (95% CI, 5.6-13.8) vs 4.27 months (95% CI, 2.8-7.3); the HR of 0.70 favored the TPST-1120 arm, although investigators noted that it was not yet mature. The median OS in each respective arm was not reached (NR; 95% CI, 10.84 -NR) vs 15.1 months (95% CI, 7.49-NR). The HR for OS was 0.59, which was not mature.

Among 7 patients with b-catenin activating mutations, the experimental triplet yielded a confirmed ORR of 43% and a disease control rate (DCR) of 100%. Additionally, it was reported that the confirmed ORR was 27% with the triplet vs 7% in the control arm among a subgroup of patients with PD-L1–negative tumors.

In the experimental and control arms, respectively, 40.0% and 16.7% of patients were on treatment, and 72.5% and 46.7% of patients were on study. Investigators disclosed that safety findings were similar between the 2 treatment arms.

“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,” Stephen Brady, president and chief executive officer at Tempest, said in the press release. “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.”

In the international randomized phase 1b/2 trial, investigators are assessing TPST-1120 in combination with atezolizumab and bevacizumab compared with atezolizumab plus bevacizumab in those with unresectable or metastatic HCC who have not received any prior systemic therapy. Patients were randomly assigned to receive 1200 mg of intravenous atezolizumab every 3 weeks plus 15 mg/kg of intravenous bevacizumab every 3 weeks with or without 1200 mg of TPST-1120 orally once a day.

The study’s primary end point is investigator-assessed ORR per RECIST v1.1 criteria. Secondary end points include PFS, OS, DOR, DCR, and safety.

Patients 18 years and older with histologically or cytologically confirmed locally advanced or metastatic and/or unresectable HCC and an ECOG performance status of 0 or 1 were eligible for enrollment on stage 1 of the trial. Additional eligibility criteria for stages 1 and 2 included having measurable disease per RECIST v1.1 criteria, adequate hematologic function, documented virology status of hepatitis, and a negative human immunodeficiency virus test at screening.

Reference

Tempest releases new data demonstrating superiority of TPST-1120 arm across multiple study endpoints in randomized first-line HCC study. News release. Tempest Therapeutics. October 11, 2023. Accessed October 12, 2023. https://shorturl.at/euxDL