Golcadomide (GOLCA), a potential, first-in-class, oral CELMoD™ agent, ± rituximab (R) in patients with Relapsed/Refractory follicular lymphoma (R/R FL): Phase 1/2 study extended follow-up Results

作者：Julio C. Chávez, Jason R. Westin, Javier Muñoz, Emmanuel Bachy, Judit Jørgensen, Guilherme Fleury Perini, Daniel Morillo, Abel Costa, Parth Rao, Bérengère de Moucheron, Gang Yang, Soraya Carrancio, Akshay Sudhindra, Michael Pourdehnad, Jessica Voetsch, Serena Perna, Jean‐Marie Michot · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-1006 · 被引用次数：1 · 研究领域：CAR-T cell therapy research、Lymphoma Diagnosis and Treatment、Chronic Lymphocytic Leukemia Research

Abstract Introduction While outcomes in patients with R/R FL have improved with T-cell–redirecting treatments (e.g. CAR T-cell therapy, bispecific antibodies), there remains an unmet need for safe, efficacious, and more convenient chemotherapy-free treatment options (Caridà et al, Eur J Haematol. 2025). GOLCA is a potential, first-in-class, oral CELMoD agent designed for the treatment of lymphoma, with preferential distribution to lymphoid organs and enhanced activity in lymphoma cell lines. GOLCA drives the closed, active conformation of cereblon to induce rapid and deep degradation of Ikaros and Aiolos, leading to direct cell killing (agnostic of cell of origin) and immunomodulatory activity. In the two-part, multicenter, first-in-human Phase 1/2 study (CC-99282-NHL-001; NCT03930953), GOLCA was well tolerated and effective in patients with R/R FL (Cordoba et al, ICML 2025, #441). Here, we provide longer follow-up in patients with R/R FL from Part B of the study. Methods Patients with R/R FL with ≥ 2 prior lines of therapy (≥ 1 in Part B if prior anti-CD20 therapy) were included in the study. Patients received GOLCA monotherapy orally, once daily at different dosing schedules in Part A. In Part B, GOLCA was dosed at 0.2 or 0.4 mg (14 days on/14 days off) ± R. Total GOLCA treatment duration was up to 2 years or until progressive disease (PD)/unacceptable toxicity. Primary objectives included safety and recommended Phase 2 dose determination. Results As of April 3, 2025, a tot...