Another Roche MAGE-A4 trial disappears, withdrawn without enrolling after strategic review

Roche has made another MAGE-A4 program disappear, withdrawing a phase 1 trial of a T-cell bispecific prospect before a single patient was enrolled.

The withdrawal, which ApexOnco reported earlier this week, followed a series of delays to the start date of the trial. Roche’s Genentech unit had planned to start testing the MAGE-A4xCD3 bispecific in solid tumor patients in July but pushed the date back over the summer.

“We made the decision to discontinue the GO44669 study as a result of a strategic review of our development efforts,” a spokesperson confirmed to Fierce Biotech. “The decision was not related to any preclinical safety or efficacy concerns. For now, we have stopped development of RO7617991 and are assessing next steps.”

Genentech withdrew the trial around a year after its parent company Roche pulled the plug on a study of RO7444973, another MAGE-A4 bispecific. That asset, like RO7617991, was designed to hit MAGE-A4 on tumor cells and CD3 on T cells. The mechanism could activate and redirect cytotoxic T-lymphocytes to cancer cells that express MAGE-A4, driving the destruction of the tumor.

The withdrawal of the RO7617991 trial completed a hat-trick of setbacks for Roche’s work on MAGE-A4. The first domino fell in April 2023, when Roche dropped its MAGE-A4 HLA-A02 soluble TCR bispecific in the wake of phase 1 ovarian cancer data. Immunocore, which licensed the candidate to Genentech, had already withdrawn co-funding for the program by the time Roche published details of its decision.

Roche’s missteps have thinned the pack of active MAGE-A4 programs. Adaptimmune continues to study its FDA-approved MAGE-A4 therapy Tecelra and next-generation uza-cel. Marker Therapeutics is running a phase 1 trial of a T-cell therapy that targets six tumor-associated antigens, including MAGE-A4, while CDR-Life started a phase 1 study of its MAGE-A4 bispecific earlier this year.