BTK Inhibitor M7583 Shows Significant Benefit in B-Cell Lymphomas in Phase 1 Trial

BTK Inhibitor M7583 Shows Significant Benefit in B-Cell Lymphomas in Phase 1 Trial

Bruton’s tyrosine kinase (BTK) inhibitor M7583 is proving to be safe and beneficial in patients with refractory or resistant B-cell lymphomas, according to an ongoing Phase 1 trial.

Updated trial data on the investigational therapy was recently discussed at the European Society for Medical Oncology (ESMO) 2018 Congress in Munich in a poster presentation titled “Phase I/II, first in human trial with M7583, a Bruton’s tyrosine kinase inhibitor (BTKi), in patients with B cell malignancies.”

BTK is a key protein that B-cells need to thrive and multiply. By blocking this molecule, M7583 is expected to kill cancer B-cells and prevent B-cell lymphomas from progressing.

Other BTK inhibitors, like Imbruvica (ibrutinib), are already approved for B-cell cancers, such as chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenström’s macroglobulinemia (WM).

M7583 is a highly selective BTK inhibitor developed by Merck KGaA (known as EMD Serono in the U.S. and Canada) that has shown promising anti-tumor activity in preclinical studies.

Now researchers have been exploring its benefits in patients with B-cell lymphomas who received one to three prior cancer treatments in a Phase 1/2 trial (NCT02825836).

In Phase 1 of the trial, patients received increasing daily doses of M7583 — starting at 80 mg for the first three days followed by 160 mg, up to 900 mg — to determine the treatment’s safety and the recommended dose for further testing.

Data from the first 14 patients included in this part have demonstrated that M7583 is generally safe and well-tolerated, with evidence of clinical benefits in all doses tested.

The study included four patients with WM, six with MCL, two marginal zone lymphoma (MZL) patients, one with CLL, and another with diffuse large B-cell lymphoma (DLBCL).

Overall, adverse events were mild to moderate in intensity, with no dose-limiting toxicities reported. Six patients had a total of eight severe to life-threatening adverse events, but only one was considered to be related to the treatment. The most common adverse events were diarrhea, dizziness, dry skin, fatigue, itchy skin, vomiting, and inflammation of the nasal cavities and pharynx.

M7583 was also found to either stop the disease from progressing or reduce the tumor burden in 86% of patients, including a complete response seen in a patient receiving 600 mg once daily. In addition, six patients achieved a partial response, two had a minor response, and three patients achieved stable disease with no signs of cancer progression.

Phase 1 is ongoing, with an additional dose still under investigation. Researchers will soon begin Phase 2 of the trial to continue studying the safety and efficacy of the recommended dose in patients with relapsed or refractory DLBCL and MCL.

“M7583 has been well tolerated with evidence of clinical benefit at all the doses investigated. M7583 appears to have a favorable benefit:risk profile,” the researchers concluded.

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