Golcadomide (GOLCA), a potential, first-in-class, oral CELMoD, plus rituximab (R) versus investigator’s choice (IC) in patients (pts) with relapsed/refractory follicular lymphoma (R/R FL) who have received ≥ 1 line of systemic therapy: GOLSEEK-4, a phase (Ph) 3, randomized study.

Abstract

TPS7102 Background: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma (NHL), typically presenting as advanced-stage at diagnosis. With current SOC (chemoimmunotherapy [CIT] and maintenance), many pts can achieve remission; however, FL remains incurable, with shorter remissions and overall survival (OS) following relapses. Treatments for R/R FL, including CIT or R-lenalidomide (R 2 ), offer limited long-term benefit. T-cell-redirecting therapies in ≥ 3L provide better efficacy but are limited by tolerability and logistical challenges. An unmet need persists for effective, well-tolerated, convenient options for R/R FL pts after ≥1L of systemic therapy. GOLCA is a potential, first-in-class, oral CELMoD designed for the treatment of lymphoma, with preferential distribution to lymphoid organs and enhanced activity in lymphoma cell lines. GOLCA induces rapid and deep degradation of Ikaros and Aiolos, leading to direct cell killing and immunomodulatory activity. GOLCA 0.4 mg + R was studied in heavily pre-treated R/R FL pts (including those given lenalidomide [LEN] and T-cell redirecting therapies) in the Ph 1/2 CC-99282-NHL-001 study, resulting in objective response rate 97%, complete response rate 78% and tolerable safety, suggesting benefit vs SOC (Chavez et al., ASH 2025, #1006). As a result, the Ph 3 study, GOLSEEK-4 (NCT06911502) was initiated. Methods: GOLSEEK-4 is a global, randomized, Ph 3 study evaluating fixed-duration, chemo-free GOLCA + R vs IC (R 2 or R-chemo) in R/R FL after ≥1 prior lines of therapy. Included: adults (≥18 yr) with grade 1-3A R/R FL or cFL, PET-positive disease with measurable lesions (Lugano criteria), ECOG 0–2 (or 3 if due to lymphoma), require treatment based on modified GELF, and ≥1 prior regimen, including anti-CD20 + alkylating agent. Prior T-cell-redirecting therapy allowed. Excluded: composite DLBCL/FL, transformed NHL, CNS involvement, those who are R/R or intolerant to all options in IC arm. Approximately 400 pts will be randomized 1:1 to GOLCA (0.4 mg QD, Days 1–14 per 28-day cycle) + R for 5 cycles, then GOLCA monotherapy for 7 cycles (12 cycles total) or IC (R 2 for 5 cycles then LEN monotherapy for 7 cycles, or R-CHOP or R-Bendamustine for 6 cycles). Randomization will be stratified by disease progression within 24 months (mo) vs >24 mo from initial CIT, prior lines (2L vs 3L+), and IC regimen. Pts will be followed for at least 5 yrs. Recruitment began July 2025. Primary endpoint: progression-free survival (IRAC). Secondary endpoints: overall response rate (IRAC), OS, complete metabolic response, minimal residual disease, time to next therapy, duration of response. Safety is exploratory. Acknowledgement: BMS ChatGPT4 used to revise existing text with human author input (Jan 26). Clinical trial information: NCT06911502 .