Amgen and CytomX throw off masked T-cell engager, axing asset after assessing data, priorities

Amgen and CytomX Therapeutics have kicked a phase 1 T-cell engager to the curb, axing the asset after assessing the clinical data and their pipeline priorities.

CytomX signaled the EGFRxCD3 bispecific candidate CX-904 was on thin ice in January. Back then, the biotech said plans to complete a phase 1a trial and move into phase 1b were pending. The uncertainty stemmed from capital constraints that prompted CytomX to lay off 40% of its staff and consider how to spend its remaining dollars.

Now, CX-904 has fallen off CytomX’s list of priorities. CytomX CEO Sean McCarthy said on an earnings call that his team and Amgen “jointly decided” against further development based on “clinical observations to date and our respective priorities.”

CX-904 was the first masked T-cell engager that CytomX took into the clinic. The masking technology is designed to render the bispecific inactive until it reaches the tumor microenvironment. Enzymes found at high concentrations around tumors cut a linker, causing the mask to drop and the bispecific antibody to bind to CD3 on T cells and EGFR on cancer cells. CytomX still believes in the core concept.

“We continue T-cell engager discovery work with Amgen,” McCarthy said. “We remain optimistic about the potential of future masked T-cell engagers and really look forward to making additional progress on this modality within our partnerships.”

Axing CX-904 eliminates one of a band of EGFR bispecifics. A Chinese hospital is studying SMET12, an EGFRxCD3 bispecific, in non-small cell lung cancer. Other groups are developing molecules that engage EGFR and receptors other than CD3. Regeneron is running a phase 2 trial of a EGFRxCD28 asset. Pfizer has a bispecific that is designed to turn Vγ9Vδ2 T cells against EGFR-positive tumors in phase 1.