Shattuck Labs has opened a Phase 1 clinical trial to investigate its lead candidate, SL-172154, in treating people with advanced ovarian cancer, the company announced in a press release. The trial (NCT04406623) is recruiting up to 33 patients at three sites in the U.S.: the John Wayne Cancer Institute at Providence St. John's Health Center in California, START Midwest in Michigan, and the Stephenson Cancer Center at Oklahoma University. For more information, click here. SL-172154 is designed to modulate a patient's immune system to destroy cancer cells, unlike many treatments that directly target cancer cells. Developed with Shattuck's agonist redirected checkpoint (ARC) platform, the candidate is essentially a fusion protein that binds to two distinct proteins in cells. One is the CD47 molecule on cancer cells that interacts with the SIRPα protein at the surface of macrophages, specialized immune cells that engulf invaders. Through this interaction, cancer cells send a "don't eat me" signal to macrophages, allowing them to avoid targeting. The second is the CD40 tumor necrosis factor (TNF) stimulatory receptor at the surface of T-cells, which are immune cells involved in the fight against cancer. By binding to this receptor, SL-172154 is intended to prime T-cells to better eliminate cancer cells. By promoting the activation of both macrophages and T-cells, SL-172154 bridges two types of immune responses: the innate, or first-line and general, immune response, and the acquired, or adaptive and specialized, immune response. Preclinical work found this approach more effective than antibodies targeting the CD47 and CD40 receptors. “In preclinical studies, SL-172154 demonstrated superior anti-tumor activity as compared to either CD47- or CD40-targeted antibodies, either alone or in combination," said Taylor Schreiber, MD, PhD, CEO of Shattuck. "Based on its ability to simultaneously block the CD47/SIRPα checkpoint and activate the CD40 costimulatory receptor, we believe SL-172154 offers a promising approach to treating patients with ovarian cancer and a range of other cancer types,” Schreiber added. The ongoing trial is enrolling people with inoperable, locally advanced, or metastatic ovarian cancer, primary peritoneal cancer, or fallopian tube cancer who are not eligible for platinum-based chemotherapy. Treatment will be administered intravenously to patients, grouped by ascending doses, with the goal of finding the safest and most effective dose for a future Phase 2 study. More patients may be enrolled to continue studying the selected dose. The trial, which runs through July 2022, also aims to evaluate the overall safety, tolerability, and anti-tumor effects of SL-172154. Researchers anticipate releasing initial trial data late next year. “We are incredibly excited to have now initiated this clinical trial evaluating SL-172154 in patients with ovarian cancer, where there remains a high unmet need for effective new therapies,” said Lini Pandite, MD, chief medical officer of Shattuck. Shattuck also plans to evaluate SL-172154 in combination with other therapies. It is currently investigating a similar compound, SL-279252, in a Phase 1 trial (NCT03894618) in people with advanced solid tumors and lymphomas. SL-279252 also binds the CD40 receptor, but blocks a different mechanism used by cancer cells to evade immune responses, the PD-1/PD-L1 signaling pathway. The trial, conducted in collaboration with Takeda Pharmaceuticals, is recruiting participants in the U.S., Canada, and Europe; more information is available here.