Abstract
Background: CELESTIMO (NCT04712097) is a randomized, multi-center, Phase III study evaluating the efficacy and safety of Mosun-Len vs rituximab plus lenalidomide in patients with R/R FL. The non-randomized, single arm US extension (Arm C) of CELESTIMO further evaluates the efficacy and safety of Mosun-Len in US patients. We report the focused enrollment strategies implemented in Arm C, and preliminary efficacy and safety outcomes.
Methods: To overcome enrollment barriers in the US for CELESTIMO, several targeted recruitment strategies were introduced. Key measures included the expansion of the US site footprint to include community sites and locations that were not historically participating in clinical trials; conducting a dedicated US-focused investigator meeting with comprehensive training; creating tailored materials based on investigator feedback; engaging investigators and site staff through 1:1 interaction; customized recruitment strategies for individual sites; and centralized support for patients and caregivers to ease participation challenges. In this non-randomized, single arm US extension, patients received intravenous mosunetuzumab plus oral lenalidomide, as described for Arm A by Nastoupil et al. 2022 (J Clin Oncol). Preliminary efficacy was evaluated by investigator-assessed objective response rate (ORR) and complete response rate (CRR), using Lugano criteria (Cheson et al. J Clin Oncol 2014). Safety objectives included incidence and severity of adverse events (AEs) and cytokine release syndrome (CRS), according to the Common Terminology Criteria for Adverse Events v5.0 and the American Society for Transplantation and Cellular Therapy grading criteria (Lee et al. Biol Blood Marrow Transplant 2019), respectively.
Results: At data cut-off (June 9, 2025), 54 patients were enrolled in the US extension Arm C of the CELESTIMO trial. Enrollment took place between September 2023 and December 2024, highlighting the success of the focused recruitment strategies, which streamlined the recruitment process and were instrumental in achieving rapid enrollment and demographic representation of the US population of patients with FL. Overall, 87.0% (47/54) of patients identified as White, 5.6% (3/54) as Asian, 3.7% (2/54) as African American, and 1.9% (1/54) as mixed race (American Indian/White); 22.2% (12/54) of patients identified as Hispanic or Latino. Median age was 62 years (range: 37–82); 59.3% (32/54) of patients were male; 40.4% (21/52) had a Follicular Lymphoma International Prognostic Index score of ≥3; 29.6% (16/54) had progressive disease within 24 months of first systemic therapy; 39.6% (19/48) were refractory to prior anti-CD20 therapy; and 17.0% (9/53) of patients had double-refractory disease.
Median duration of follow-up was 12.7 months (range: 5–20). ORR was 96.3% (n=52/54; 95% confidence interval [CI] 90.3–100.0) and CRR was 87.0% (n=47/54; 95% CI 75.1–94.6).
All patients experienced at least one AE (any grade) and 57.4% experienced a Grade (Gr) 3–4 AE. Serious AEs occurred in 27.8% of patients, and 11.1% and 18.5% of patients had an AE that led to mosunetuzumab and lenalidomide withdrawal, respectively. AEs related to mosunetuzumab and lenalidomide were reported in 88.9% and 92.6% of patients, respectively. One fatal mosunetuzumab-related AE (pneumonia) occurred. CRS was reported in 27.8% of patients (Gr 1, 22.2%; Gr 2, 3.7%; Gr 3, 1.9%); all CRS events resolved. Median duration of CRS was 4 days (range: 1–23). Neutropenia occurred in 40.7% of patients (Gr 1, 3.7%; Gr 2, 3.7%, Gr 3, 22.2%; Gr 4, 11.1%) and febrile neutropenia occurred in 3.7% of patients (all Gr 3). Infections were reported in 57.4% of patients (most common: COVID-19, 20.4%; sinusitis, 18.5%; upper respiratory tract infection, 16.7%) and were mainly Gr 2 (44.4%) in severity.
Conclusions: The rapid and successful enrollment to the US extension of CELESTIMO may provide a roadmap for addressing challenges in clinical trial recruitment. Insights gained from this experience underscore the importance of patient-centric approaches for improving trial accessibility and ensuring demographic representation. Preliminary data support the potential for Mosun-Len as an effective and well-tolerated outpatient combination treatment for US patients with R/R FL. Continued efforts to address patient-, site-, and system-level barriers to trial participation are essential for advancing innovative therapies and improving outcomes for US patients with FL.
