Phase 1b/2 Study of MK-1045 Monotherapy and MK-1045 Plus Tocilizumab in Adults with Relapsed/Refractory Non‑Hodgkin Lymphoma

Primary objective: Evaluate the safety and tolerability of MK‑1045 monotherapy administered intravenously or subcutaneously, and determine the overall response rate in participants with Non‑Hodgkin Lymphoma using Lugano Response Criteria, with assessment performed by blinded independent central review or investigator as specified by study arm.

Secondary objectives:

• Assess duration of response per Lugano criteria as reviewed by BICR (arms 1 and 4).
• Assess duration of response per Lugano criteria as evaluated by investigator or designee (arms 2 and 3).
• Characterize the pharmacokinetic profile of MK‑1045 following intravenous administration (arms 1, 2, and 4).
• Characterize the pharmacokinetic profile after subcutaneous injection (arm 3).
• Determine overall response rate for subcutaneous monotherapy using Lugano criteria as assessed by investigator or designee (arm 3).

The trial enrolled 139 individuals diagnosed with Non‑Hodgkin Lymphoma, specifically histologically confirmed follicular lymphoma or diffuse large B‑cell lymphoma, who had experienced disease relapse or were refractory after at least two prior systemic therapies. Both female and male patients were eligible, encompassing the adult age categories defined in the protocol. Participants were selected based on documented disease progression, measurable lesions per Lugano Response Criteria, and availability of tumor tissue confirming CD19 expression when required. Additional health considerations included well‑controlled HIV infection on antiretroviral therapy, undetectable hepatitis B or C viral loads with appropriate antiviral treatment, and prior ineligibility for transplant or CAR‑T therapy in the DLBCL subgroup. General health status required adequate organ function to permit study drug administration, while no specific lifestyle restrictions such as diet or physical activity were mandated in the protocol.

The study is a Phase 1b/2, multicenter, open‑label, multi‑arm trial evaluating the safety, tolerability, and efficacy of MK‑1045 administered intravenously or subcutaneously as monotherapy in participants with Non‑Hodgkin Lymphoma. Eligible individuals are allocated to one of four treatment arms: three arms receive MK‑1045 intravenously (with two arms differing by response assessment method) and one arm receives MK‑1045 subcutaneously. The trial incorporates a screening visit to confirm eligibility, a baseline visit for study drug administration, regular treatment visits for dosing and safety assessments, scheduled follow‑up visits to monitor disease response per Lugano Response Criteria, and a final end‑of‑study visit after the last dose. Primary endpoints focus on adverse events, dose‑limiting toxicities, and objective response rate, while secondary endpoints include duration of response and pharmacokinetic parameters. Participant involvement extends from the screening visit through the end‑of‑study assessment, with the overall study period spanning from the planned recruitment start on 8 June 2026 to the projected completion on 21 October 2030. Early termination criteria include discontinuation due to adverse events, dose‑limiting toxicity, disease progression, or voluntary withdrawal.

The investigational agent MK-1045 is supplied as a sterile solution for infusion. In Arms 1, 2 and 4 the product is administered intravenously (IV) as monotherapy; in Arm 3 it is given as a subcutaneous (SC) injection. The dose level and administration schedule are defined in the protocol and are delivered on the designated study days, with each dose administered as a single infusion or injection per treatment cycle. Dosing frequency follows the study‑specified interval, and the infusion or injection is performed under clinical supervision with pre‑ and post‑administration safety assessments.

The auxiliary agent tocilizumab is provided in the pharmaceutical form identified as PHF00231MIG. It is administered according to its approved indication and used as a background therapy where indicated. The route of administration is consistent with its labeled use, and dosing follows standard clinical practice guidelines; no specific dose is mandated by the trial protocol.

Participants receive no additional investigational anticancer agents; standard supportive care and any required concomitant medications are permitted per institutional guidelines. Compliance with study drug administration is monitored through infusion logs, injection records, and scheduled pharmacokinetic sampling. Vital signs and laboratory parameters are assessed before and after each administration to ensure adherence to safety monitoring requirements.

Efficacy is primarily assessed by the Objective Response Rate determined according to the Lugano Response Criteria. In Arms 1 and 4, response evaluations are performed by a blinded independent central review (BICR), whereas in Arm 2 (and Arm 3 for the subcutaneous formulation) the investigator or designated assessor conducts the evaluation.

A secondary efficacy measure is the Duration of Response, also defined by the Lugano Response Criteria and assessed by the same review method as the primary endpoint for each respective arm.