Cambritaxestat Wins FDA Orphan Drug Designation in Pancreatic Cancer

• Cambritaxestat has received FDA orphan drug designation for the potential treatment of patients with pancreatic cancer.
• This agent is the first autotaxin inhibitor to be explored in patients with cancer.
• A phase 1 study titled AION-02 (NCT05586516) is currently evaluating cambritaxestat in combination with chemotherapy in patients with metastatic pancreatic cancer.

An orphan drug designation has been granted to the autotaxin inhibitor cambritaxestat by the FDA for the treatment of patients with pancreatic cancer.¹

"There is an urgent need to develop new therapies for pancreatic cancer which is currently the third largest cause of death by cancer in the [United States] and the fourth in Europe. Although survival of patients with pancreatic cancer has improved in recent years, it still stands at just 13% after 5 years. This orphan drug designation will support our goal to accelerate cambritaxestat through the clinic to provide a new treatment to patients with limited options," said Catherine Pickering, chief executive officer of iOnctura, in a press release.

Cambritaxestat is an orally dosed molecule that is being developed as a first-in-class therapy for highly fibrotic cancer indications that overexpress autotaxin, including pancreatic, liver, colorectal, ovarian, and breast cancers. Targeting autotaxin is an emerging approach to treatment and works in 3 ways: directly hindering cancer cell growth, boosting immune effector stimulation, and preventing scar tissue formation, which allows drugs and immune cells to reach the tumor more effectively.

In preclinical models, the agent showed promise by slowing tumor growth and proliferation of cancer cells, attracted immune cells to attack tumors, and helped to prevent the development of fibrosis. Additionally, translational research has shown the promise of using cambritaxestat in multiple cancer models, including pancreatic cancer.

Cancer of pancreas: ©Dr_Microbe - stock.adobe.com

Findings from these studies have shown cambritaxestat to lead to a strong reduction of metastasis and tumor growth and have been published in the European Society of Medical Oncology journal Immuno-Oncology and Technology (IOTECH), Cancer Research, the Journal of Experimental & Clinical Cancer Research, and Cancers. Additionally, data on cambritaxestat has shown the potential first-in-class therapy to be safe and tolerable.

Treatment with cambritaxestat is currently undergoing evaluation in the phase 1 AION-02 trial where it is being investigated in combination with chemotherapy in metastatic pancreatic cancer. The study began in Q4 2022.

Additionally, the World Health Organization has proposed the international nonproprietary name of cambritaxestat.

About the Phase 1 Study of Cambritaxestat in Pancreatic Cancer

The AION-02 trial aims to assess the safety and tolerability of escalating doses of cambritaxestat in patients with metastatic pancreatic cancer when given in combination with standard chemotherapy, which consists of gemcitabine and nab-paclitaxel. In the study, investigators will collect blood and tumor samples for pharmacokinetics (PK) and pharmacodynamics (PD).² Assessments for determination of any clinical efficacy will also be done.

Enrollment in the study is open to patients aged 18 years and older with histologically or cytologically confirmed metastatic unresectable pancreatic adenocarcinoma, an ECOG performance status of 0 to 1, and measurable disease. Patients must be eligible to receive systemic treatment in the first line with gemcitabine and nab-paclitaxel for metastatic disease, baseline CA19-9 levels should be available from a sample that was taken no more than 4 weeks prior to screening, and patients must not have undergone previous systemic anticancer therapy for metastatic pancreatic cancer.

The primary end point of the study is incidence of treatment-emergent adverse events. Secondary end points include PK, PD, overall response rate, disease control rate, duration of response, progression-free survival, and overall survival.

The estimated study completion date is February 1, 2025.

REFERENCES:

1. US FDA grants orphan drug designation for iOnctura's first-in-class autotaxin cancer therapy. News release. iOnctura. March 7, 2024. Accessed March 7, 2024. https://tinyurl.com/2txa8k6e

2. A study to assess an ATX Inhibitor (IOA-289) in patients with metastatic pancreatic cancer. ClinicalTrials.gov. Updated March 5, 2024. Accessed March 7, 2024. https://clinicaltrials.gov/study/NCT05586516?tab=table