Cambritaxestat, a treatment for metastatic pancreatic ductal adenocarcinoma (mPDAC), has met its primary endpoint in a Phase Ib trial.

Cambritaxestat, an oral autotaxin (ATX) inhibitor, was evaluated in patients with previously untreated mPDAC. The treatment demonstrated safety, tolerability and anti-tumour responses, with data presented at the European Society for Medical Oncology (ESMO) Congress in Berlin, Germany. 

The Phase Ib dose escalation study evaluated cambritaxestat in combination with standard-of-care chemotherapy GnP in patients with previously untreated mPDAC. Sixteen patients received cambritaxestat orally, twice daily at doses of 100mg (n=4), 200mg (n=4), 400mg (n=5) and 800mg (n=3). GnP was administered by IV infusion, weekly for three weeks of a four-week cycle.  

The results show no dose-limiting toxicities and no treatment-emergent adverse events (TEAE) leading to drug discontinuation or dose modification. Pharmacodynamic analysis showed a dose dependent reduction in the ATX-dependent plasma lipid LPA C18:2 over 24 hours supporting cambritaxestat’s on-target effects. Patients in the higher-dose cohorts had consistent and durable reductions of the tumour marker CA19-9. These changes were associated with radiographic responses and survival. 

“These early findings with cambritaxestat are encouraging,” said Davide Melisi, Lead Investigator and Director of the Digestive Molecular and Clinical Oncology Research Unit at the University of Verona, Italy.  

“Clinical activity alongside a manageable safety profile is particularly meaningful in a disease as aggressive and fibrotic as metastatic pancreatic cancer. These findings warrant continued scientific exploration in autotaxin inhibition.” 

“As we advance development, we remain focused on unlocking the potential of cambritaxestat to improve outcomes for patients facing some of the most challenging and hard-to-treat cancers,” added Dr Michael Lahn, Chief Medical Officer at iOnctura.  

Cambritaxestat is the first autotaxin inhibitor to be investigated in cancer patients and is being developed as a first-in-class therapy across multiple cancer indications. This study was co-funded by the European Union and recruited patients in Italy and the United Kingdom. 

Bruno Quinney, Content Team, DDW