Phase 2/3 Randomized Open‑Label Study of MK‑1045 Versus Blinatumomab in Relapsed/Refractory CD19‑Positive B‑Cell Acute Lymphoblastic Leukemia

Primary objectives focus on establishing the recommended phase 2 dose (RP2D) of MK‑1045 and its comparative efficacy and safety in relapsed/refractory B‑cell acute lymphoblastic leukemia. The aims are to:

• Evaluate the RP2D and RP2D‑1 of MK‑1045 with respect to complete remission (CR) in Part 1.
• Assess the safety and tolerability of the RP2D and RP2D‑1 of MK‑1045 in Part 1.
• Compare MK‑1045 to blinatumomab regarding CR in Part 2.
• Compare MK‑1045 to blinatumomab regarding overall survival (OS) in Part 2.

Secondary objectives include:

• Evaluate the RP2D and RP2D‑1 of MK‑1045 with respect to overall survival (OS) in Part 1.
• Assess MRD negativity of MK‑1045 at the RP2D and RP2D‑1 in Part 1.
• Evaluate CR/CRh/CRi rates of MK‑1045 at the RP2D and RP2D‑1 in Part 1.
• Compare MK‑1045 to blinatumomab for MRD negativity in Part 2.
• Compare MK‑1045 to blinatumomab for CR/CRh rates in Part 2.
• Compare MK‑1045 to blinatumomab for CR/CRh/CRi rates in Part 2.
• Determine the duration of CR, CR/CRh, and CR/CRh/CRi in Part 2.
• Assess event‑free survival (EFS) in Part 2.
• Evaluate the proportion of patients undergoing allo‑HSCT after randomisation in Part 2.
• Assess the safety and tolerability of MK‑1045 in Part 2.

The study enrolled 240 participants diagnosed with relapsed/refractory B-cell Acute Lymphoblastic Leukemia. Eligible individuals were ≥ 12 years of age, included both males and females, and demonstrated CD19‑positive, Philadelphia‑negative disease with ≥ 5 % lymphoblasts in the bone marrow. Enrollment required recovery from adverse events related to prior anticancer therapy to ≤ Grade 1. The cohort spanned pediatric, adolescent, and adult age groups, reflecting the reported age‑range codes, and all subjects satisfied the disease‑specific inclusion criteria; no additional lifestyle restrictions were specified.

The study is a Phase 2/3 randomized, open‑label, controlled trial comparing the investigational agent MK‑1045 with the comparator blinatumomab in participants diagnosed with relapsed/refractory B‑cell Acute Lymphoblastic Leukemia. After a screening visit confirming eligibility, participants receive the assigned intravenous infusion and undergo a baseline assessment, followed by scheduled treatment cycles during which efficacy (including complete remission) and safety are evaluated. Subsequent follow‑up visits continue until the end‑of‑study visit, which occurs after the final treatment cycle to collect long‑term data such as overall survival. Individual participation extends from the screening visit through the end‑of‑study assessment, approximately 12–15 months in duration. Early termination is permitted for protocol‑defined reasons, including Grade ≥ 3 treatment‑related adverse events, disease progression, withdrawal of consent, or failure to meet required laboratory or clinical criteria. The overall trial recruitment period is projected from June 2026 to January 2036.

The investigational product, MK-1045, is supplied as a solution for infusion for intravenous administration. The formulation is presented as a % (V/V) percent volume/volume solution with a nominal concentration of 0 % V/V. Dosing is planned based on the identified recommended phase 2 dose (RP2D) and RP2D‑1, administered by continuous intravenous infusion. The infusion schedule, frequency, and duration are defined in the protocol and are adjusted according to safety and pharmacokinetic assessments. Compliance is monitored through infusion pump logs and periodic review of infusion records.

The comparator arm receives blinatumomab, a bispecific T‑cell engager indicated for CD19+ B‑Cell Acute Lymphoblastic Leukemia. Blinatumomab is provided as the pharmaceutical form PHF00230MIG for intravenous use. The administered dose is 28 µg per infusion, delivered as a continuous intravenous infusion. Infusions are performed daily according to the study‑specified cycle, with dose adjustments permitted for toxicity. Adherence is tracked by documenting each infusion in the electronic case report form and by reviewing drug accountability logs.

Tocilizumab, classified as an auxiliary background therapy, is supplied as the pharmaceutical form PHF00231MIG for intravenous use. The product is a % (V/V) solution with a nominal concentration of 0 % V/V and is administered intravenously when indicated by the protocol, typically for management of cytokine release syndrome. Dosing intervals and duration follow the predefined algorithm in the study protocol. Administration details are recorded in the participant’s medication log, and compliance is verified through source documentation.

Efficacy will be evaluated primarily by the proportion of participants achieving complete remission (CR) within the first three treatment cycles for both study parts. In Part 2, overall survival (OS) will also be assessed as a primary efficacy endpoint.

Secondary efficacy assessments include overall survival, the percentage of participants attaining minimal residual disease (MRD) negativity, and the rates of CR with partial hematologic recovery (CRh) or incomplete count recovery (CRi) within the first three cycles. Additional secondary measures comprise the duration of CR, CRh, and CRi, event‑free survival, and the proportion of participants proceeding to allogeneic hematopoietic stem cell transplantation. Efficacy evaluations will be performed at the end of each treatment cycle, with data collected and analyzed according to the predefined study schedule.