Molecular Partners Revises Tetra-Specific Dosing After 'Suboptimal Exposure' in Cancer Trial

Molecular Partners has identified ineffective exposure to its tetra-specific T-cell engager as the possible reason for the limited response rate in its early-phase trial. Consequently, the Swiss biotech company is modifying the protocol to increase the impact of the compound. The candidate, MP0533, includes six binding domains: three that target CD33, CD123, and CD70 on tumor cells, one that engages T cells by targeting CD3, and two that extend the half-life of the candidate in circulation. The goal is to destroy cancer cells expressing two or more antigens while sparing healthy cells that express only one.

The candidate is currently being tested in a phase 1/2a study involving patients with relapsed or refractory acute myeloid leukemia and myelodysplastic syndrome. As of July 29, four clinical responses were observed among 28 patients treated in the first six dose cohorts. Philippe Legenne, M.D., recently appointed as Molecular Partners’ permanent chief medical officer, presented the interim data during an earnings call. He noted that while the company has seen some responses, it needs more to fully unlock the potential of the compound.

Molecular Partners has identified “suboptimal exposure” as a barrier to the candidate's full potential. This realization has led the company to revise the protocol to permit higher and more frequent dosing, aiming to enhance the response rate, response depth, and durability. Currently, investigators are enrolling patients in the eighth dose cohort, with the potential to reach the eleventh dose level.

Dr. Legenne explained, “What we hope is that we are going to reduce the tumor burden. We see that we have more responses in the lower tumor burden than in the higher.” He also emphasized the importance of avoiding chronic exposure to prevent T-cell exhaustion, stating, “We wouldn’t want to be continuous all the time. Then the question is how little is enough.”

A key question remains whether increasing the dose will improve responses. One complete response was seen at the fourth dose level, and cases of morphologic leukemia-free state were observed at the third, fifth, and sixth doses. Data collection is ongoing for the seventh dose, but there is currently no clear correlation between dose and response.