Trishula Therapeutics Reports Positive Phase 1 Results for TTX-030 in Metastatic Pancreatic Cancer

Trishula Therapeutics, Inc., a biotechnology firm based in South San Francisco, recently shared the final results from a Phase 1 trial of TTX-030, an anti-CD39 antibody, at the European Society for Medical Oncology (ESMO) Congress 2024 in Barcelona. This trial targeted patients with first-line metastatic pancreatic cancer.

Anil Singhal, the Chief Executive Officer of Trishula Therapeutics, highlighted the trial’s success in improving median overall survival rates for these patients. The positive results, especially in those exhibiting high levels of tumor HLA-DQ biomarker expression, have paved the way for the global, randomized Phase 2 ELTIVATE study, with outcomes anticipated in 2026.

The Phase 1 trial involved TTX-030 in combination with gemcitabine/nab-paclitaxel, with or without the investigational anti-PD-1 antibody budigalimab, as a primary treatment for pancreatic adenocarcinoma. The efficacy-evaluable population consisted of 57 patients, with 92% having first-line metastatic and 8% having locally advanced non-resectable cancer. Key findings included a 30% objective response rate (ORR) with three complete responses. Median progression-free survival (mPFS) was recorded at 7.5 months, and median overall survival (mOS) was 19.1 months.

A notable observation was the performance in a subset of patients with high HLA-DQ biomarker expression (HLA-DQhigh). Among these 28 patients, the ORR was 46%, mPFS was 9.6 months, and mOS reached 21.9 months. The treatment combinations were generally well-tolerated, with only 8% of patients discontinuing due to adverse events (AEs). The most common AEs were consistent with those expected from standard chemotherapy without any notable increase in frequency or severity.

Zev Wainberg, MD, from UCLA, emphasized the need for new approaches in treating this patient group, given the limited benefits seen with prior immune checkpoint treatments. The encouraging results from this trial, particularly in biomarker-high patients, underline the potential of TTX-030 and warrant further investigation.

TTX-030 is currently undergoing evaluation in the global Phase 2 ELTIVATE trial as the first-line treatment for metastatic pancreatic adenocarcinoma. This trial will randomize about 180 patients into three study arms: TTX-030 with chemotherapy, TTX-030 plus budigalimab and chemotherapy, or chemotherapy alone. The primary endpoint is progression-free survival in a biomarker-enriched (HLA-DQhigh) population, with secondary endpoints including overall population PFS, safety, objective response rate, duration of response, and overall survival.

TTX-030 is designed to inhibit CD39, an enzyme that converts ATP to AMP, thereby reducing immune-suppressive extracellular adenosine and maintaining immune-activating extracellular ATP levels. This promotes both innate and adaptive anti-tumor immunity by stimulating dendritic and myeloid-derived cells. Trishula’s development of TTX-030 is in collaboration with AbbVie Inc.

Trishula Therapeutics remains focused on the development of TTX-030.