Carthera Starts Phase 2a Clinical Trial of SonoCloud-9

Sorbonne University spin-off company, Carthera launched a phase 2a clinical trial (NCT05864534). Northwestern University sponsors the trial and will use Carthera’s SonoCloud-9 device with Agenus’ checkpoint inhibitors balstilimab and botensilimab in patients with newly diagnosed glioblastoma (GBM) who have completed radiotherapy.
 
The trial will be conducted in Chicago, Northwestern University, and will use Agenus’ multifunctional Fc-enhanced anti-CTLA-4, botensilimab, and anti-PD-1 bastilimab, in combination with Carthera’s implantable ultrasound device SonoCloud-9. This will open the Blood-Brain Barrier (BBB), allowing for better penetration of drug molecules into the brain.
 
“Our SonoCloud-9 device, that temporarily opens the blood-brain barrier, provides opportunities for entirely novel treatments against glioblastoma. We are excited about this trial which will, for the first time, allow the delivery of immunotherapy into large parts of the brain tissue,” said Carthera’s chief scientific officer, Dr. Michael Canney.
 
SonoCloud-9 has been tested extensively in phase 1/2 trials in combination with different chemotherapy regimens for patients with recurrent glioblastoma. The phase 2a trial will assess the efficacy and safety of immune-modulating checkpoint therapies for the treatment of GBM when combined with BBB opening. This pilot trial aims to recruit 25 patients to assess safety and preliminary efficacy.  
 
Participating patients who have completed radio chemotherapy will be enrolled within three to four weeks and will then receive treatment with Carthera’s SonoCloud-9 device along with low-dose liposomal doxorubicin, to modulate the tumor microenvironment, and Agenus’ checkpoint inhibitors balstilimab and botensilimab.
 
The use of this ultrasound-based device to open the BBB has been shown to enhance the delivery of monoclonal antibodies to disease sites within the brain. Low-dose doxorubicin is also used to further enhance the immune response.
 
“Our preclinical data has provided new insights into the mechanism of action and combined activity of immunotherapy and ultrasound. Our preclinical results are encouraging and we are excited to move this approach forward to benefit our patients,” said Dr. Adam Sonabend, associate professor of neurological surgery at Northwestern University Feinberg School of Medicine and the lead neurosurgeon and investigator on this trial.
 
Dr. Sonabend’s lab at Northwestern University has carried out extensive preclinical work on the use of the SonoCloud-9 device in the treatment of GBM, which forms the strategy for this new trial.
 
“This approach has the potential to transform the standard of care for patients suffering from glioblastoma, in particular for patients with tumors harboring an unmethylated MGMT promoter, who have a particularly poor prognosis,” said Dr. Roger Stupp, professor of medicine (hem/onc), neurology and neurological surgery and medical director of the Malnati Brain Tumor Institute of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University. 
 
Dr. Stupp was the lead investigator on the trials that led to the FDA approval of the current standard of care using temozolomide, and Tumor Treating Fields (TTF).
 
“This collaboration with Agenus and Northwestern illustrates the combinational potential of the SonoCloud device with various innovative therapeutic agents and opens new perspectives for patients with glioblastoma. It further confirms Carthera’s position as a leader in the development of therapeutic ultrasound for the treatment of brain diseases,” said Carthera CEO, Frederic Sottilini.