MSD said its newly acquired T-cell engager has demonstrated acceptable tolerability and safety in relapsed or refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL), despite all patients experiencing adverse events.
During the Phase Ib/II MK-1045-002 dose escalation study (NCT05579132), MK-1045, a CD3×CD19-targeting T-cell-engager bispecific antibody, triggered treatment-emergent adverse events (TEAEs) in 100% of the 75 patients enrolled on the study, with Grade 3-5 events occurring in 67 (89%) of those receiving the therapy.
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Most AEs were managed with dose modifications and standard medical care, and none required treatment discontinuation.
There was one death during the study period related to a haemoptysis event, which MSD determined was unrelated to treatment with MK-1045.
While cytokine release syndrome was observed in 45% (34) of patients across all study cohorts, most were Grade 1 or 2, with two events classified as Grade 3. It was a similar case for neurotoxicity AEs, which were all mild-to-moderate in the 11 patients who experienced them.
Treatment interruption occurred in 33% (25) of patients in the study while dose reduction due to an AE occurred in one patient. No dose-limiting toxicities occurred within the study, and the maximum tolerated dose (MTD) was not reached.
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By GlobalDataMK-1045 demonstrated promising early efficacy signals, triggering complete remission (CR), CR with incomplete haematologic recovery (CRi) or CR with partial haematologic recovery (CRh) in 55% of 73 patients who were efficacy evaluable.
Of the 24 patients who received the target dose of ≥60mg, 83% (20) achieved CR/CRi/CRh, with a median duration of complete remission (DoCR) in this population reaching 11.3 months. Of these 20 patients, 18 achieved minimal residual disease (MRD) negativity.
MK-1045’s efficacy was observed in patients who had received a median of two prior lines of therapy.
The results of the MK-1045-002 study were first debuted in an oral presentation at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition, which is being held between 6-9 December in Orlando, Florida.
Merck & Co (MSD) previously gained the rights to MK-1045 from Shanghai-based biotech, Curon Pharmaceutical, for up to $1.3bn in 2024.
Next steps for MK-1045
Moving forward, Dr Gregory Lubiniecki, VP, global clinical development at MSD, told Clinical Trials Arena that the company plans to determine the optimal dose for MK-1045 in B-ALL.
Once a dose is selected, Lubiniecki noted that MSD will then consider initiating Phase III studies involving the drug.
When asked if MSD may explore MK-1045’s potential in the frontline setting, Lubiniecki noted that the company was “keeping an open mind”, as several ongoing clinical trials explore the role of T-cell engagers in the first line setting.
Alongside MSD’s development efforts for MK-1045 in B-ALL, the pharma is evaluating the therapy’s potential in both r/r B-cell non-Hodgkin lymphoma (B-NHL) and r/r diffuse large B-cell lymphoma (DLBCL).
This led Lubiniecki to highlight the potential versatility of the drug, which displayed “similar tolerability” across all three indications.
Chemotherapy’s future in B-ALL
Currently, the B-ALL treatment paradigm centres around a chemotherapy regimen in the first line, though there are immunotherapies such as Amgen’s Blincyto (bilnatumomab) and Pfizer’s Besponza (inotuzumab), which are approved for use in relapsed or refractory patients.
Some companies have been looking to upgrade or replace traditional chemotherapy regimens with more targeted alternatives, with next-generation biologics such as T-cell engagers, CAR-Ts and bispecific antibodies all drawing interest.
While targeted therapeutic advancements are being made in the haematological oncology segment, Lubiniecki noted that cytotoxic therapy may still be needed in the initial setting, as the goal is to “eradicate all of the disease quickly to allow patients to achieve complete remission”.
Currently, the best-selling targeted drug in B-ALL is Blincyto, which made $1.2bn for Amgen in 2024. Analysts at GlobalData forecast that the therapy will generate $2.1bn in global sales in 2031.
GlobalData is the parent company of Clinical Trials Arena.
