318 | PHASE 2/3 waveLINE‐003 STUDY: ZILOVERTAMAB VEDOTIN PLUS STANDARD OF CARE IN RELAPSED OR REFRACTORY DIFFUSE LARGE B‐CELL LYMPHOMA
Makaleler > Tam Makale · 2025
Yazarlar: P. Armand, S. T. Lee, W. Jurczak, D. Stevens, S. Choquet, H. Ghesquieres, L. Norasetthada, A. Pinto, Güray SAYDAM, H. Zhou, N. Reddy, R. Yusuf, M. Ozcan
Hematological Oncology, Uluslararası, Wos, 2025, cilt 43
Özet
Introduction: Clinical outcomes for patients with R/R DLBCL remain poor.Zilovertamab vedotin (ZV) is a novel ROR1-targeting antibody-drug conjugate that has shown promising efficacy in DLBCL.The phase 2/3 waveLINE-003 (NCT05139017) study was designed to evaluate ZV plus rituximab and gemcitabine-oxaliplatin (R-GemOx) in participants (pts) with R/R DLBCL.Results from the dose confirmation phase of the study are reported.Methods: Eligible pts were aged ≥ 18 y, had confirmed R/R DLBCL after ≥ 1 prior line of therapy, and were ineligible for or did not respond to prior treatment with chimeric antigen receptor T-cell therapy (CAR-T) or autologous stem-cell transplant (ASCT).During dose confirmation, pts received ZV at 1.5, 1.75, or 2.0 mg/kg plus rituximab 375 mg/m 2 , gemcitabine 1000 mg/m 2 , and oxaliplatin 100 mg/m 2 every 3 weeks for 6 cycles.The primary end points were safety and the recommended phase 2 dose (RP2D) of ZV with R-GemOx.Secondary end points were overall survival (OS), and objective response rate (ORR) and duration of response (DOR) per Lugano criteria by central review.Results: Forty pts were enrolled and received ZV plus R-GemOx: 17 pts (43%) received ZV 1.5 mg/kg, 16 pts (40%) received ZV 1.75 mg/kg, and 7 pts (17%) received ZV 2.0 mg/kg.Twenty-two pts (55%) were aged ≥ 65 years, 8 (20%) had relapsed at > 12 mo, and the median number of prior therapies was 2. Seven pts (18%) received prior CAR-T and 7 (18%) received prior ASCT.Median study follow-up at data cutoff (Aug 1, 2024) was 9.8 mo.ZV dose-limiting toxicities occurred in 7 pts (1.5 mg/kg, n = 1; 1.75 mg/kg, n = 2; 2.0 mg/kg, n = 4).Any-grade treatment-related adverse events (AEs) occurred in 39 pts (98%); most commonly, diarrhea (n = 18 [45%]), nausea (n = 15 [38%]), anemia (n = 11 [28%]), and decreased platelet count (n = 11 [28%]).Grade 3-5 treatment-related AEs occurred in 26 pts (65%); most commonly, neutropenia (n = 9 [23%]), decreased neutrophil count (n = 9 [23%]), decreased platelet count (n = 9 [23%]), and anemia (n = 8 [20%]).One grade 5 treatment-related AE occurred in the 2.0 mg/kg dose cohort (sepsis).Two pts discontinued due to treatment-related AEs (sepsis, respiratory failure).The RP2D was determined to be 1.75 mg/kg.ORRs were 27% in the 1.5 mg/kg dose cohort (4/15 evaluable pts; 3 complete responses [CRs], 1 partial response [PR]), 56% in the 1.75 mg/kg dose cohort (9/16 evaluable pts; 8 CR, 1 PR) and 57% in the 2.0 mg/kg dose cohort (4/7 evaluable pts; 3 CRs, 1 PR); median DOR was 14.4 mo, 8.7 mo, and not reached (NR) in each dose group, respectively.Median OS was 11.5 mo (1.5 mg/kg), NR (1.75 mg/kg), and 7.4 mo (2.0 mg/kg); 6-mo OS rates were 70.0%, 78.8%, and 68.6%, respectively.Conclusions: ZV plus R-GemOx had a manageable safety profile and promising efficacy in pts with R/R DLBCL at the RP2D of ZV 1.75 mg/kg.The randomized phase 3 portion of the study will proceed to evaluate ZV plus R-GemOx versus R-GemOx alone.