A combination of botensilimab and balstilimab is demonstrating encouraging results in the treatment of sarcomas, offering new hope for patients with this rare cancer that originates in bones, muscles, blood vessels, and connective tissues. The ongoing phase one, multi-site trial indicates that these drugs are particularly effective in cancers that do not respond well to traditional immunotherapy.
Breelyn Wilky, MD, a member of the University of Colorado Cancer Center and principal investigator for the phase one study, notes, "We are extending the reach of the immunotherapy to 'cold tumors,' or tumors that are not particularly well recognized by the immune system."
Mechanism of Action
The experimental combination features botensilimab, an antibody that targets cytotoxic T-lymphocyte antigen 4 (CTLA4). According to Dr. Wilky, CTLA4 is crucial for T cell education, enabling them to learn from macrophages and dendritic cells about which cells to target.
The second drug, balstilimab, is a monoclonal antibody that binds to the programmed cell death 1 (PD-1) receptor on T-cells. By blocking PD-1, balstilimab prevents tumor cells from sending inhibitory signals that would otherwise prevent T cells from attacking.
"When you already have T cells that know what they're supposed to be killing, and they're face to face with the tumor cell, blocking PD 1 gets rid of that checkpoint where the tumor says, 'Don't eat me,'" Wilky explains. "When you get rid of that, the immune cells that are already educated can then kill the tumor cell."
Clinical Trial Results
In the clinical trial, patients receive both drugs sequentially, with balstilimab administered every two weeks and botensilimab every six weeks. While the treatment has shown promise across all sarcoma patients, it has been particularly effective in those with angiosarcoma.
"The response rate was 23% for all of the sarcoma patients, but we are really excited about the results in the angiosarcoma subtype, which is very hard to treat," Wilky stated at the European Society for Medical Oncology Congress in Barcelona. "We got a 44% response rate in that group in particular, which is promising, because that's generally a super-immune cold tumor where we wouldn't have expected immunotherapy to work."
Future Directions
While a specific trial for angiosarcoma patients may be conducted in the future, Dr. Wilky is currently overseeing a separate trial to evaluate the efficacy of the balstilimab-botensilimab combination in conjunction with chemotherapy for newly diagnosed sarcoma patients.
"There's no approved checkpoint inhibitor for sarcomas, so there is a huge unmet need," she emphasizes. "We've had patients in both trials with metastatic sarcoma who historically would never have been cured. Chemo could slow it down, but they wouldn't be cured."
Approval of this drug combination could pave the way for further research into its application across various sarcoma subtypes. The initial findings suggest potential benefits in leiomyosarcoma, where responses to immunotherapy are not typically observed.
