Westin, Jason

LBA7000 Background: ~40% of DLBCL pts are not cured with first-line (1L) R-CHOP, underscoring a significant unmet need for more effective 1L regimens. Tafa (anti-CD19 mAb) + Len-R-CHOP in the phase 1b First-MIND study demonstrated safety and efficacy in pts with newly diagnosed disease. frontMIND, a phase 3, double-blind, placebo-controlled study, compared Tafa-Len-R-CHOP vs R-CHOP in pts with high-risk aggressive BCLs. Methods: Pts aged 18–80 y with newly diagnosed, high-intermediate/high-risk DLBCL or HGBL (IPI 3–5, aaIPI 2–3 if ≤60 y) and ECOG PS 0–2 were randomized 1:1 to Tafa-Len-R-CHOP or R-CHOP. Primary endpoint was investigator-assessed PFS; secondary endpoints included: EFS, OS, CR, ORR, safety. Results: At primary analysis (data cutoff Oct 20, 2025), 899 pts were randomized to Tafa-Len-R-CHOP (n=448) or R-CHOP (n=451); baseline characteristics were similar between arms. With a median follow-up of 35.2 mo, Tafa-Len-R-CHOP achieved a statistically significant improvement in PFS vs R-CHOP (HR 0.75 [95% CI: 0.59, 0.96]; P =0.019) in the overall population; in pts with centrally confirmed lymphoma subtypes (n=773), PFS HR was 0.68 (95% CI: 0.52, 0.88) and 24-mo PFS was 72.7% vs 62.2%. PFS benefit was observed with Tafa-Len-R-CHOP in both molecular COO subtypes, ABC and GCB (data will be presented). Tafa-Len-R-CHOP significantly improved EFS vs R-CHOP; CR and ORR were similar between arms and HR for OS was 0.85 (final OS planned at 5y) (Table). Any-grade TEAEs were similar in treatment arms (98.6% vs 97.1%); more grade ≥3 TEAEs occurred with Tafa-Len-R-CHOP vs R-CHOP (86.7% vs 76.1%). Discontinuations due to TEAEs occurred in 25.7% vs 17.9% and deaths due to TEAEs in 5.9% vs 3.8% of pts for Tafa-Len-R-CHOP vs R-CHOP. Overall, there were fewer deaths with Tafa-Len-R-CHOP vs R-CHOP (18.5% vs 21.7%). Conclusions: The primary endpoint of frontMIND was met; Tafa-Len-R-CHOP resulted in a significant 25% reduction in risk of disease progression or death compared with R-CHOP, with an 8.2% difference in 24-month PFS rate in the overall population and 10.5% difference in pts with centrally confirmed lymphoma subtypes. TEAEs were manageable and consistent with the expected safety profile. Tafa-Len-R-CHOP represents a potential new 1L standard of care for pts with both COO subtypes of high-risk DLBCL or HGBL. Clinical trial information: NCT04824092 . Efficacy outcomes by treatment arm.* Variable Tafa-Len-R-CHOP(n=448) R-CHOP(n=451) HR or OR(95% CI) P value PFS, # events (%) † 121 (27.0) 155 (34.4) 0.75 (0.59, 0.96) 0.019 PFS rate at 24 mo, % 71.1 62.9 − − PFS rate at 36 mo, % 67.3 60.7 − − EFS, # events (%) 154 (34.4) 191 (42.4) 0.79 (0.64, 0.97) 0.026 OS, # events (%) 82 (18.3) 95 (21.1) 0.85 (0.63, 1.14) 0.270 CR at EOT, n (%) 292 (65.2) 294 (65.2) 0.998 (0.76, 1.31) 0.987 ‡ ORR at EOT, n (%) 360 (80.4) 343 (76.1) 1.290 (0.94, 1.78) 0.120 ‡ *Investigator-assessed. † Progressive disease or death from any cause. ‡ Nominal P value.

e19046 Background: While outcomes in pts with R/R FL have improved with current SOC treatments (Tx), there remains a need for safe, efficacious, and convenient Tx options. GOLCA is a potential, first-in-class, oral CELMoD designed for Tx 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 + R was well tolerated and effective in heavily pretreated pts in the two-part Ph 1/2 study, CC-99282-NHL-001. Here, we provide longer f/u in pts with R/R FL from Part B of the study. Methods: Pts with R/R FL with ≥2 prior lines of Tx (≥1 if prior anti-CD20 Tx) received GOLCA orally, once daily at 0.2 mg (n=22) or 0.4 mg (n=38) ± R for up to 2 y or until progressive disease (PD)/unacceptable toxicity. Primary endpoints included safety and RP2D determination; secondary endpoints are preliminary efficacy and PK. Results: As of September 15, 2025, 60 pts were enrolled. In 0.2 and 0.4 mg groups, median prior Tx lines were 3 and 3, 32% and 32% had prior lenalidomide (LEN), 27% and 29% had prior T-cell–redirecting Tx (CAR T and/or bispecific antibody) and 32% and 32% were refractory to last regimen. Tx is ongoing in 6 (27%) and 17 (45%) pts at 0.2 and 0.4 mg, respectively; discontinuations (d/c) were mostly due to PD. Neutropenia, an on-target side effect of GOLCA, was the most common grade 3/4 Tx-emergent adverse event (TEAE) occurring in 59% and 68% of pts at 0.2 and 0.4 mg, followed by anemia (9% and 16%) and febrile neutropenia (9% and 8%). Median time to resolution of neutropenia was 8 days. Dose reductions occurred in 14% and 37% of pts at 0.2 and 0.4 mg, most commonly due to neutropenia (5% and 21%) and febrile neutropenia (5% and 5%). No d/c or deaths were from GOLCA-related TEAEs. Non-hematologic TEAEs were infrequent and mostly low grade. In efficacy-evaluable pts (GOLCA 0.2 and 0.4 mg + R, n=22 and n=36), median f/u was 14.03 months (mo), overall response rate (ORR) was 77% (complete response rate [CRR], 41%) at 0.2 mg, and 97% (CRR, 78%) at 0.4 mg. In the 0.4 mg group, responses were consistent in high-risk subsets including pts with prior LEN (ORR, 100%; CRR, 75%) and/or T-cell–redirecting Tx (ORR, 91%; CRR, 64%). GOLCA 0.4 mg + R demonstrated durable responses (median DOR, 9.17 mo; 91% of pts who achieved a CR remained in CR at cutoff). Conclusions: With longer f/u, GOLCA + R demonstrated promising efficacy with durable responses and no new safety signals. The 0.4 mg group had higher ORR and CRR than 0.2 mg, including in pts with prior LEN-based and/or T-cell–redirecting Tx, with a manageable safety profile at both doses. The results support the development of GOLCA + R as a fixed-duration, chemotherapy-free outpatient Tx in the Ph 3 GOLSEEK-4 study in 2L+ FL (NCT06911502). Clinical trial information: NCT03930953 .