Phase 2/3 Randomized Open‑Label Study of MK‑1045 Combined with Rituximab Versus Standard Chemotherapy Plus Rituximab in First‑Line Follicular Lymphoma

Primary objective: In Part 1, the study evaluates the safety and tolerability of MK‑1045 in combination with rituximab and assesses the rate of complete response (CR) according to Lugano criteria as determined by the investigator. In Part 2, the trial compares MK‑1045 + rituximab with physician‑chosen chemotherapy + rituximab with respect to progression‑free survival (PFS) per Lugano criteria, adjudicated by blinded independent central review. These endpoints address the therapeutic benefit and risk profile of the investigational regimen in first‑line follicular lymphoma.

Secondary objectives include: – evaluation of overall response (OR) per Lugano criteria; – determination of the duration of CR; – characterization of the pharmacokinetic (PK) profile of MK‑1045; – assessment of CR at 30 months, OR, overall survival (OS), and event‑free survival (EFS) by blinded independent central review; – comparison of CR duration between treatment arms; – continued evaluation of safety and tolerability; – measurement of changes from baseline in health‑related quality of life using the FACT‑Lym instrument.

The trial enrolled 33 participants diagnosed with biopsy‑proven, previously untreated, CD19‑positive and CD20‑positive Follicular Lymphoma. Both male and female patients were included; the sponsor did not provide a specific age range. Eligible subjects required radiographically measurable disease according to Lugano criteria and a recent core, excisional, or archival tumor biopsy that had not been previously irradiated. Individuals with well‑controlled HIV on antiretroviral therapy, those with suppressed hepatitis B virus infection receiving antiviral treatment for at least four weeks, and those with undetectable hepatitis C virus RNA were also permitted. The population comprised patients in generally good health aside from the lymphoma diagnosis, and selection was based on the defined histologic and virologic criteria without additional lifestyle restrictions.

The study is a Phase 2/3, randomized, open‑label, integrated trial evaluating MK-1045 in combination with rituximab versus physician‑choice chemotherapy plus rituximab in patients with previously untreated follicular lymphoma. After an initial screening visit to confirm eligibility, participants undergo a baseline visit (Day 1) where the first infusion of study medication is administered. Subsequent treatment visits occur at regular intervals (e.g., every 21 days) for the duration of the assigned regimen, with safety assessments, laboratory tests, and imaging performed at each visit to monitor response per Lugano criteria. Follow‑up visits are scheduled every 3 months after the last treatment dose to assess long‑term outcomes, including the primary efficacy endpoint of progression-free survival. The overall participant involvement may extend up to 30 months, concluding with an end‑of‑study visit that includes final efficacy and safety evaluations. Early termination may occur if a participant experiences a dose‑limiting toxicity, an adverse event leading to discontinuation of study treatment, disease progression, or withdraws consent.

MK-1045 is an investigational agent supplied as a solution for infusion for intravenous administration. The specified concentration is expressed as a percentage volume/volume (0 % V/V) and the dosing schedule, including frequency and cycle length, is defined in the study protocol.

Rituximab is a chimeric anti‑CD20 monoclonal antibody provided in multiple commercial concentrates for solution for infusion (500 mg and 100 mg). It is administered intravenously; the concentration is expressed as 0 % V/V and dosing is performed on the designated treatment days according to the protocol. Products used include Truxima 500 mg, Truxima 100 mg, Ruxience 500 mg, Ruxience 100 mg, and a reference rituximab preparation.

Tocilizumab is included as an auxiliary agent. It is supplied in a pharmaceutical preparation (PHF00231MIG) and administered by the route specified in the protocol.

Comparator chemotherapeutic agents are administered intravenously as follows:

• Doxorubicin hydrochloride – 50 mg/m² per infusion.
• Bendamustine hydrochloride – 90 mg/m² per infusion.
• Cyclophosphamide – 750 mg/m² per infusion.
• Vinorelbine – 1.4 mg/m² per infusion.

Oral corticosteroid therapy is provided as prednisone (prednisolone) at a dose of 40 mg/m², administered orally on the days indicated in the protocol.

Efficacy is primarily assessed through disease‑response endpoints defined by the Lugano response criteria. Complete Response (CR) rate is evaluated by the physician investigator in Part 1, while Progression‑Free Survival (PFS) is determined by blinded independent central review (BICR) in Part 2. Additional efficacy parameters include Objective Response Rate (ORR), duration of CR, CR rate at 30 months, Overall Survival (OS), and Event‑Free Survival (EFS). These endpoints are measured using standard radiologic and clinical assessments performed at protocol‑specified intervals throughout treatment and follow‑up.

Health‑related quality of life is evaluated with the Functional Assessment of Cancer Therapy‑Lymphoma (FACT‑Lym) questionnaire. Changes from baseline are calculated for the Trial Outcome Index (TOI), the total score, and the Physical Well‑Being (PWB) subscale (items GP1–GP7). Data are collected at designated study visits and analyzed according to the instrument’s scoring guidelines.