WaveLINE-003: Phase 2/3 trial of zilovertamab vedotin plus standard of care in relapsed/refractory diffuse large B-cell lymphoma.
Bildiriler > Özet Bildiri
Yazarlar: Philippe Armand, Seung Tae Lee, Wojciech Jurczak, Don A. Stevens, Sylvain Choquet, Hervé Ghesquieres, Lalita Norasetthada, Antonio Pinto, Güray SAYDAM, Heng Zhou, Nishitha Reddy, Rushdia Zareen Yusuf, Muhit Ozcan
Journal of Clinical Oncology, , , Uluslararası, Özet Bildiri, Scopus, cilt 43, ss 7005-7005
DOI: 10.1200/jco.2025.43.16_suppl.7005
Özet
7005 Background: Outcomes for patients relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) remain poor. Zilovertamab vedotin (ZV) is a novel ROR1-targeting antibody-drug conjugate that has shown promising efficacy in patients with DLBCL. Here we present results of the dose confirmation part of the waveLINE-003 (NCT05139017) trial evaluating ZV plus rituximab and gemcitabine-oxaliplatin (R-GemOx) in pts with R/R DLBCL. Methods: The phase2/3 trialwaveLINE-003 enrolled adult participants (pts) with confirmed R/R DLBCL after ≥1 lines of therapy (LOT) who were ineligible for chimeric antigen receptor T-cell therapy (CAR-T), autologous stem-cell transplant (ASCT), or failed such therapies (cohort A). In the dose confirmation phase, eligible pts received ZV (1.5, 1.75, or 2.0 mg/kg) plus R-GemOx Q3W for ≥6 cycles. Primary endpoints were safety and recommended phase 2 dose (RP2D). Secondary endpoints were objective response rate (ORR) and duration of response (DOR) per Lugano 2014 response criteria by central review, and overall survival. Results: At data cut-off date (August 1, 2024),40 pts had been enrolled in cohort A to receive R-GemOx plus ZV 1.5 mg/kg (n=17), 1.75 mg/kg (n=16), or 2.0 mg/kg (n=7); 22 (55%) were ≥65 years old, and 8 (20%) relapsed >12 mo. Median number of prior LOTs was 2.0 with 7 (18%) pts receiving prior CAR-T, and 7 (18%) receiving prior ASCT. Median follow-up was 9.8 months (mo). Seven DLTs (1 for ZV [1.5 mg/kg], 2 for ZV [1.75 mg/kg], and 4 for ZV [2.0 mg/kg]) were reported. Treatment-related adverse events (AE) were reported in 39 (98%) pts; the most common being diarrhea (n=18 [45%]), nausea (n=15 [38%]), anemia (n=11 [28%]), and platelet count decrease (n=11 [28%]). Grade ≥3 treatment-related AEs were reported in 26 (65%) pts, the most common being neutropenia (n=9 [23%]), neutrophil count decreased (n=9 [23%]), platelet count decreased (n=9 [23%]), and anemia (n=8 [20%]). Two pts discontinued due to AE (sepsis and respiratory failure, both treatment-related), and 1 pt died due to sepsis (treatment related), all in the 2.0 mg/kg dose cohort. The RP2D was determined to be 1.75 mg/kg. ORR was 27% (3 CR, 1 PR [ZV 1.5 mg/kg]), 56% (8 CR, 1 PR [ZV 1.75 mg/kg]), and 57% (3 CR, 1 PR [ZV 2.0 mg/kg]), with median DOR of 14.4 mo, 8.7 mo and not reached (NR), respectively. Median overall survival was 11.5 mo (ZV 1.5 mg/kg), NR (ZV 1.75 mg/kg), and 7.4 mo (ZV 2.0 mg/kg), with 6-month OS rate of 70.0%, 78.8%, and 68.6%, respectively. Conclusions: Zilovertamab vedotin in combination with R-GemOx demonstrated promising efficacy and acceptable safety in R/R DLBCL at the RP2D of ZV of 1.75 mg/kg plus R-GemOx. The study is proceeding to the phase 3 portion randomizing patients to ZV-RGemOx versus RGemOx. Clinical trial information: NCT05139017 .