A phase 3 trial of MacroGenics’ margetuximab in HER2-positive metastatic breast cancer patients has met its primary endpoint. The anti-HER2 antibody improved progression-free survival by more than Herceptin, teeing MacroGenics up to file for approval in the second half of the year.
Margetuximab goes after the same target as Roche’s Herceptin but also features a tail-end Fc portion intended to activate immune effectors. The idea is to marry the apoptosis and signaling effects that made Herceptin a success to mechanisms that turn the immune system against tumors.
That idea now has the validation of phase 3 data. The study enrolled 536 patients and randomized them to receive either margetuximab or Herceptin on top of a chemotherapy regimen. All subjects had previously taken Herceptin and Roche’s Perjeta, another HER2 drug that is given in combination with Herceptin. Patients who received margetuximab had a 24% risk reduction in PFS compared to patients on Herceptin, resulting in a p value of 0.033.
Most of the subjects carried the CD16A 158F allele, a marker associated with weak responses to Herceptin. In this predefined subpopulation, margetuximab was associated with a 32% PFS risk reduction.
MacroGenics is still waiting for the overall survival data to mature but thinks it has the basis for a BLA. If approved, margetuximab could fill a gap in the breast cancer care pathway.
“There are currently no approved agents for the treatment of patients with metastatic HER2+ breast cancer who have previously received trastuzumab, pertuzumab and ado-trastuzumab emtansine. If margetuximab is approved, … I believe that this agent could become a valuable treatment option for these patients,” Hope Rugo, M.D., of the University of California San Francisco Comprehensive Cancer Center said in a statement.
MacroGenics’ share price soared in premarket trading following the release of the data. How important a drug margetuximab is will only become clear as MacroGenics shares more details of the top-line results and the OS data matures. But the PFS results represent success against an early yardstick.