GSK Halts Cancer Drug Trial Based on Australian Research

A human trial for nelistotug, a cancer drug developed by GSK, has been terminated. The drug sponsor initiated the trial in 2023 with 316 volunteers diagnosed with head and neck cancers across Europe and America.

The cancellation of the GALAXIES H&N-202 phase II trial occurred after an interim analysis indicated no clinically meaningful improvement in the primary endpoint, the objective response rate. The drug's development was based on research by Australian scientist Mark Smyth.

The Research Behind Nelistotug

The foundation for GSK's drug development came from the work of Mark Smyth, who was previously a prominent cancer researcher in Australia. Smyth faced accusations of research misconduct in 2021, leading to a referral to state corruption authorities.

Smyth's research focused on a cell receptor known as CD96. His 2014 paper in Nature Immunology suggested a crucial mechanism:

CD96 binding to CD155 on cancerous cells was hypothesized to deactivate the immune response, thereby allowing tumors to grow. Blocking this interaction was believed to enable the immune system to target cancer cells more effectively.

Trial Outcomes and Implications

The GALAXIES H&N-202 phase II trial, originally scheduled to run until 2027, was prematurely halted due to these unpromising early results. A spokeswoman for GSK confirmed the program's termination, stating it was based on the interim analysis showing a lack of meaningful improvement.

A former colleague of Smyth's, who had collaborated on CD96 research, expressed sadness for the volunteers. However, they also stated they were not surprised by the drug's failure, as they had been unable to replicate Smyth's initial promising laboratory results.

The colleague commented on "the waste of money and false hope provided to patients," suggesting it serves "as a warning if all positive results originate from a single research group."

Despite Mark Smyth's career issues, GSK had proceeded with the nelistotug trial. Other pharmaceutical companies, including Bristol Myers Squibb, have also invested in developing CD96 antibodies. GSK itself filed a patent for a CD96 antibody in 2020 and acquired rights for a CD155-targeting drug in 2021, reflecting broader industry interest in this pathway.