Lyell Immunopharma has acquired exclusive global rights, excluding mainland China, Hong Kong, Macau, and Taiwan, to a next-generation CAR T-cell therapy in clinical development for metastatic colorectal cancer. The product candidate, LYL273 (formerly GCC19CART), targets guanylyl cyclase-C (GCC), a receptor expressed in the majority of colorectal cancers and some pancreatic adenocarcinomas. The therapy incorporates additional design features intended to enhance T-cell expansion and persistence in the solid tumor environment.
The candidate was originally developed by Innovative Cellular Therapeutics (ICT), from which Lyell has obtained the rights. Under the terms of the agreement, Lyell will make an upfront payment of $40 million in cash and issue 1.9 million shares of its common stock. ICT may also receive up to $30 million in clinical milestone payments, up to $115 million tied to regulatory milestones, and up to $675 million in commercial milestones, in addition to potential royalties ranging from mid-single digits to 10 percent in the US and lower rates in other territories.
Interim data from a phase I clinical trial, involving 12 patients with advanced metastatic colorectal cancer, showed an overall response rate of 50 percent and a disease control rate of 83 percent across two dose levels. At the higher dose, the overall response rate was 67 percent and median progression-free survival was 7.8 months. Reported treatment-related adverse events included cytokine release syndrome, diarrhea, and neurotoxicity, with one treatment-related death attributed to fungal sepsis. No further cases of severe diarrhea were reported after adjustments to patient management protocols.
"We rarely see such deep and durable responses in colorectal cancer patients treated with multiple prior lines of chemotherapy. The outcomes in this initial cohort of heavily pre-treated patients are very encouraging," said Benjamin L. Schlechter, Senior Physician in the Gastrointestinal Cancer Center, Dana-Farber Cancer Institute and Assistant Professor of Medicine at Harvard Medical School, Boston, and lead investigator in the phase I study. “Patients with metastatic colorectal cancer have a tremendous need for innovations like LYL273, and I look forward to partnering with the Lyell team as we work to rapidly deliver on the potential of this innovative cellular therapy for patients with advanced colorectal cancer.”
Lyell stated that the ongoing trial will continue dose escalation to determine the recommended dose for phase II evaluation, with an updated data readout expected in the first half of 2026. The company indicated that its current cash position is expected to support operations into 2027, covering the continued development of both LYL273 and its large B-cell lymphoma candidate, rondecabtagene autoleucel.