Golcadomide (CC-99282) CELMoD + rituximab drives 97% ORR/78% CR in heavily pretreated R/R follicular lymphoma

Golcadomide (GOLCA; CC-99282) is an oral cereblon E3 ligase modulator (CELMoD) that degrades Ikaros/Aiolos to combine direct tumor cell killing with immunomodulatory effects; in the Phase 1/2 CC-99282-NHL-001 study (Part B; NCT03930953), patients with R/R FL after ≥2 prior lines (median 3; 27%–29% post CAR T/bispecific; 32% LEN-exposed; 32% refractory to last regimen) received GOLCA 0.2mg (n=22) or 0.4mg (n=38) daily ± rituximab for up to 2 years. In efficacy-evaluable patients treated with GOLCA+R (0.2mg n=22; 0.4mg n=36; median follow-up 14.0 months), ORR/CRR were 77%/41% (0.2mg) and 97%/78% (0.4mg), including high-risk subsets at 0.4mg (LEN-exposed ORR 100%/CRR 75%; prior T-cell–redirecting therapy ORR 91%/CRR 64%); median DOR at 0.4mg was 9.17 months with 91% of CRs ongoing at data cutoff (Sep 15, 2025). Grade 3/4 neutropenia was the dominant on-target toxicity (59%–68%), with febrile neutropenia 8%–9%, dose reductions 14% (0.2mg) vs 37% (0.4mg), and no discontinuations or deaths attributed to GOLCA-related TEAEs; non-hematologic TEAEs were infrequent/low grade—this response depth is in the same ballpark as best-in-class later-line options like axi-cel in ZUMA-5 (ORR ~92%–94%, CR ~74%–79%) but with very different logistics/toxicity (cell therapy) and appears higher than fixed-duration mosunetuzumab’s pivotal dataset (ORR ~78%–80%, CR ~60%) in ≥3L FL.