On September 16, 2024 Trishula Therapeutics, Inc., a clinical stage, privately held biotechnology company, reported final results from a Phase 1 trial of TTX-030, a potential first-in-class, anti-CD39 antibody, in patients with first-line metastatic pancreatic cancer (Press release, Trishula Therapeutics, SEP 16, 2024, View Source [SID1234646673]). Results were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024 in Barcelona, Spain.

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"The Phase 1 results demonstrated a strong median overall survival in patients with metastatic pancreatic cancer following treatment with TTX-030 combinations as well as marked benefit in those with high levels of tumor HLA-DQ biomarker expression," said Anil Singhal, Chief Executive Officer of Trishula Therapeutics. "These findings have led to our currently enrolling global, randomized Phase 2 ELTIVATE study with results expected in 2026."

The Phase 1 trial evaluated TTX-030 in combination with gemcitabine/nab-paclitaxel, with or without budigalimab (an investigational anti-PD-1 antibody), as first-line treatment for pancreatic adenocarcinoma. In the efficacy-evaluable population (n=57) consisting of 92% first-line metastatic and 8% locally advanced nonresecetable patients, the objective response rate (ORR) was 30%, with 3 complete responses; the median progression free survival (mPFS) was 7.5 months (95%CI 5.2, 9.4); and median overall survival was 19.1 months (9.8, NR). Analysis of pre-treatment tumor biopsies identified a subset of patients with a high expression of an immune-associated biomarker, HLA-DQ (HLA-DQhigh) and favorable clinical outcomes with TTX-030 combinations. Of the 28 HLA-DQhigh patients, the ORR was 46%, mPFS was 9.6 months (95% CI 3.9, 11.8), and mOS of 21.9 months (9.8, NR).

Both treatment combinations were well-tolerated, with only five patients (8%) discontinuing treatment due to adverse events (AEs). The most frequent AEs were those expected from the standard of care chemotherapy backbone without an increase in frequency or severity.

"Prior evaluation of immune checkpoint treatment has demonstrated limited benefit in this patient population and new approaches are needed. These results are very encouraging, especially in the biomarker high patients and warrant further investigation of TTX-030 for patients with advanced pancreatic cancer," said Zev Wainberg, MD, Professor of Medicine, UCLA.

TTX-030 is currently being evaluated as first-line treatment for metastatic pancreatic adenocarcinoma in the global Phase 2 ELTIVATE trial (NCT06119217) that is randomizing approximately 180 patients into three study arms: TTX-030 and chemotherapy (gemcitabine and nab-paclitaxel); TTX-030 plus budigalimab and chemotherapy; or chemotherapy alone. The primary endpoint of the trial is progression-free survival (PFS) in a biomarker-enriched (HLA-DQhigh) population. Secondary endpoints include PFS in the overall population, safety, objective response rate, duration of response and overall survival. Further information on the study can be found at (clinicaltrials.gov link).

About TTX-030

TTX-030 is a potential first-in-class, anti-CD39 antibody designed to inhibit the activity of CD39, an enzyme that converts adenosine triphosphate (ATP) to adenosine monophosphate (AMP), the initial step in the generation of adenosine in the tumor microenvironment. TTX-030 prevents the formation of immune-suppressive extracellular adenosine and maintains high levels of immune-activating extracellular ATP, stimulating dendritic and myeloid-derived cells promoting both innate and adaptive anti-tumor immunity.

Trishula is continuing to develop TTX-030 in collaboration with AbbVie Inc.