Trishula Therapeutics presented positive 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 at the European Society for Medical Oncology (ESMO) Congress 2024. The trial's findings suggest a promising new approach for treating this challenging disease, particularly in patients with high expression of the HLA-DQ biomarker.
Phase 1 Trial Results
The Phase 1 trial evaluated TTX-030 in combination with gemcitabine/nab-paclitaxel, with or without budigalimab (an investigational anti-PD-1 antibody), as a first-line treatment for pancreatic adenocarcinoma. Among the efficacy-evaluable population (n=57), which consisted of 92% first-line metastatic and 8% locally advanced nonresectable patients, the objective response rate (ORR) was 30%, including 3 complete responses. The median progression-free survival (mPFS) was 7.5 months (95% CI 5.2, 9.4), and the median overall survival (mOS) was 19.1 months (9.8, NR).
Biomarker Analysis
Pre-treatment tumor biopsies revealed a subset of patients with high expression of the immune-associated biomarker HLA-DQ (HLA-DQhigh) who experienced favorable clinical outcomes with TTX-030 combinations. In the 28 HLA-DQhigh patients, the ORR was 46%, mPFS was 9.6 months (95% CI 3.9, 11.8), and mOS was 21.9 months (9.8, NR).
Safety and Tolerability
Both treatment combinations were well-tolerated, with only five patients (8%) discontinuing treatment due to adverse events (AEs). The most frequent AEs were consistent with those expected from the standard-of-care chemotherapy backbone, with no increase in frequency or severity.
Expert Commentary
"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.
Ongoing Phase 2 ELTIVATE Trial
TTX-030 is currently being evaluated as a first-line treatment for metastatic pancreatic adenocarcinoma in the global Phase 2 ELTIVATE trial (NCT06119217). This trial 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. Results from the Phase 2 ELTIVATE study are expected in 2026.
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. By inhibiting CD39, 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.
