Tempest Therapeutics, Inc. announced that Cancer Research Communications published positive clinical data from the dose-escalation Phase 1 trial of TPST-1120 in an article titled "First-in-Human Phase I Trial of TPST-1120, an inhibitor of PPARa, as Monotherapy or in Combination with Nivolumab, in Patients with Advanced Solid Tumors". The data showed that TPST-1120 demonstrated clinical activity, including tumor shrinkage, even in PD-1 inhibitor refractory and immune compromised cancers, and was well tolerated both as monotherapy and in combination with nivolumab. These earlier Phase 1 data complement the positive Phase 1b/2 data reported in October 2023 from a global randomized study of TPST-1120 In combination with atezolizumab and bevacizumab in first-line patients with advanced HCC, which showed clinical superiority of the TPST-1120 arm across multiple study endpoints and relevant biomarker-defined patient subpopulations.

TPST-1120 Phase 1 Study: In this first-in-human Phase 1 study, 35 patients were treated with escalating doses of TPST-1120 either as monotherapy (20 patients) or in combination with the anti-PD-1 therapy, nivolumab (15 patients). TPST-1120 was well-tolerated as monotherapy and in combination, with a maximum tolerated dose not identified and predominantly low-grade toxicity. Notwithstanding the late-line stage of these patients and difficult to treat tumor types, clinical benefit was observed as both a monotherapy and combination.2 In monotherapy, a best response of stable disease (SD) was observed in 53% (10/19) of evaluable patients, with 5 of those patients staying on treatment for more than 5 months.

Tumor shrinkage of target lesions on treatment occurred in 21% (4 patients) and a best response of no target lesion growth was seen in 3 additional patients. In the combination therapy cohorts, including patients with heavily pretreated cholangiocarcinoma (CCA), hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC), the objective response rate (ORR) was 23% (3/13, all partial responses, or PRs) across all dose levels and 30% (3/10) at the two highest dose levels of TPST-1120, suggesting dose-responsive anti-cancer activity. These responses included a 50% ORR in patients with RCC (2/4 evaluable) who had previously progressed on anti-PD-1 therapy, and one patient with heavily pre-treated CCA.

Analysis of whole blood specimens revealed changes in expression of PPARa-associated immune genes that were related to TPST-1120 dose levels. Some of these changes were only observed in patients who had partial responses, linking TPST-1120 biological activity to clinical outcome.