Amgen and CytomX Discontinue Development of Masked T-cell Engager CX-904

Amgen and CytomX Therapeutics have jointly decided to discontinue the development of CX-904, a phase 1 T-cell engager targeting EGFR and CD3. The decision comes after a thorough assessment of clinical data and pipeline priorities, marking a significant shift in the companies' collaborative efforts in the field of masked T-cell engagers.

Clinical Observations and Strategic Priorities

CytomX CEO Sean McCarthy revealed during a recent earnings call that the decision to axe CX-904 was based on "clinical observations to date and our respective priorities." This move follows earlier indications of uncertainty surrounding the asset, with CytomX signaling in January that plans for completing the phase 1a trial and advancing to phase 1b were pending due to capital constraints.

The discontinuation of CX-904 comes in the wake of CytomX's recent restructuring efforts, which included a 40% reduction in workforce. These measures were implemented as the company sought to optimize its resource allocation in light of financial pressures.

Masked T-cell Engager Technology

Despite the setback with CX-904, CytomX remains committed to the potential of masked T-cell engager technology. The company's innovative approach involves designing bispecific antibodies that remain inactive until they reach the tumor microenvironment. Once there, enzymes present at high concentrations around tumors cleave a linker, causing the mask to drop and allowing the bispecific antibody to bind to CD3 on T cells and EGFR on cancer cells.

McCarthy expressed ongoing optimism about the platform, stating, "We continue T-cell engager discovery work with Amgen. 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."

Landscape of EGFR-targeted Bispecifics

The discontinuation of CX-904 impacts the broader landscape of EGFR-targeted bispecific antibodies in development. Several other companies and research institutions are pursuing similar approaches:

• A Chinese hospital is currently studying SMET12, an EGFRxCD3 bispecific, in non-small cell lung cancer.
• Regeneron is conducting a phase 2 trial of an EGFRxCD28 asset.
• Pfizer has a bispecific in phase 1 trials designed to turn Vγ9Vδ2 T cells against EGFR-positive tumors.

As the field of T-cell engagers continues to evolve, the industry will be closely watching the progress of these and other innovative approaches in targeting EGFR-positive cancers.