MacroGenics has pumped the brakes on vobramitamab duocarmazine (vobra duo), pausing investment in additional opportunities for the antibody-drug conjugate (ADC) until it has updated data from a phase 2 monotherapy prostate cancer trial.
The biotech reported results from the TAMARACK trial of metastatic castration-resistant prostate cancer in September, but, at that time, the progression-free survival (PFS) data were immature. MacroGenics expects to have mature PFS data by early 2025. Until then, the biotech is hanging fire on development of vobra duo in other tumor types and in combinations.
Scott Koenig, M.D., Ph.D., who is set to step down as CEO of MacroGenics early next year, discussed the plan on an earnings call with investors after the market closed Tuesday. MacroGenics will look at the final PFS, vobra duo’s safety profile and the competitive landscape in the context of the rest of its pipeline, he said.
“It's just too early at this point to give the specific parameters which will determine next steps forward,” Koenig said. “We are looking at the final data for TAMARACK coming up in the next couple of months. We would look at the possibility of exploring additional studies in vobra to fine-tune that, if appropriate.”
The pause affects development of the B7-H3-directed ADC in different tumor types and in combination with lorigerlimab. MacroGenics will keep testing lorigerlimab, a PD-1xCTLA-4 bispecific, with docetaxel in a phase 2 prostate cancer trial that is scheduled to report data in 2025. But the biotech has paused a trial that was testing lorigerlimab with vobra duo before reaching the dose-expansion stage of the study.
“Rather than continue moving forward in expansions with the doses that we had already tested in combination, we wanted to get that final assessment of the appropriate vobra dose before we would then explore combinations going forward,” Koenig said. “So, it's a judgment that we want to ultimately have the best dose going forward if we continue combination studies.”
MacroGenics will retain an interest in B7-H3, a target pursued by other companies including Merck & Co., whatever happens to vobra duo. The biotech has another ADC, MGC026, directed at the target, plus anti-B7-H3 monoclonal antibody enoblituzumab. MGC026 uses a topoisomerase I inhibitor payload developed by Synaffix, differentiating it from vobra duo.
Koenig said there will be “distinct differences in safety,” but, with MGC026 in dose escalation, it is too early to say what they will be. Safety has been an issue for vobra duo, which sent MacroGenics’ stock tumbling in May after five patients died in the TAMARACK trial.
The biotech sees scope for the two ADCs to address different cancers and tumor stages and to be used in different combinations or with each other.