P1144: PHASE 2 WAVELINE-004 STUDY: ZILOVERTAMAB VEDOTIN (MK-2140) IN RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: DLBCL is an aggressive form of non-Hodgkin lymphoma (NHL) that is often curable with standard chemoimmunotherapy. However, 30%-40% of patients (pts) will develop R/R disease, and treatment options are limited for those who have progressed after or are not candidates for autologous stem cell transplant (ASCT) or CAR-T cell therapy. ROR1 is an oncofetal protein that is pathologically expressed in multiple hematologic malignancies including DLBCL, making it an attractive therapeutic target. Zilovertamab vedotin is a ROR1-targeting antibody-drug conjugate that had promising antitumor activity and manageable safety in pts with R/R NHL in the first-in-human, phase 1 waveLINE-001 study. The single-arm, open-label, phase 2 waveLINE-004 study (NCT05144841) is designed to evaluate the efficacy and safety of zilovertamab vedotin in pts with R/R DLBCL. Aims: To present early results from waveLINE-004. Methods: Pts were ≥18 years old and had histologically confirmed DLBCL by WHO classification that had progressed after ≥2 prior lines of therapy, including an alkylating agent, anthracycline, and an anti-CD20 antibody, and had progressed after or were ineligible for ASCT and CAR-T cell therapy. Pts were also required to have measurable disease per Lugano 2014 criteria, PET-positive disease, and an ECOG PS of 0-2. All pts received zilovertamab vedotin 2.5 mg/kg IV Q3W until disease progression, unacceptable toxicity, or patient or physician decision to withdraw. ORR per Lugano 2014 criteria was the primary end point. Safety and tolerability was secondary. Efficacy is reported for pts who had ≥3 months of follow-up. Safety is reported for all pts who received ≥1 dose of zilovertamab vedotin. Results: At the data cutoff (Nov 16, 2022), 40 pts had been enrolled and had received ≥1 dose of zilovertamab vedotin; 23 (58%) pts had discontinued treatment and 17 (43%) were ongoing. The median age was 68.0 years, 29 pts (73%) were male, 37 pts (93%) had an ECOG PS of 0 or 1, and 24 pts (60%) had received ≥3 prior lines of therapy. 10 pts (25%) had undergone prior ASCT and 11 (28%) had received prior CAR-T. Median follow-up was 2.6 months (range, 0.3-7.9) for all pts and 6.0 months (range, 3.0-7.9) for the 20 pts who had ≥3 months of follow-up (efficacy analysis population). ORR by investigator review was 30% (95% CI, 11.9-54.3), with 2 pts (10%) having a complete response and 4 (20%) a partial response; 5 pts (25%) had stable disease for a DCR of 55% (95% CI, 31.5-76.9). 28 (70%) of 40 pts experienced ≥1 treatment-related AE, most commonly (≥15%) diarrhea (9 [23%]), anemia (8 [20%]), neutropenia (7 [18%]), neutrophil count decreased (7 [18%]), and alopecia (6 [15%]). Grade 3/4 treatment-related AEs occurred in 16 pts (40%), most commonly (≥10%) neutropenia (7 [18%]), anemia (6 [15%]), and neutrophil count decreased (4 [10%]). No pts died because of treatment-related AEs. 1 pt (3%) discontinued zilovertamab vedotin because of treatment-related diabetic ketoacidosis. Treatment-related peripheral neuropathy occurred in 6 pts (15%), all of which were grade 1/2. Dose reduction was required for 3 pts (8%) because of treatment-related peripheral neuropathy. No treatment-related infusion reactions or tumor lysis syndrome occurred. Summary/Conclusion: These early results from waveLINE-004 show that zilovertamab vedotin had clinically meaningful antitumor activity and a manageable safety profile that was consistent with other monomethyl auristatin E–containing agents in pts with R/R DLBCL who had progressed after or were ineligible for ASCT and CAR-T cell therapy. © 2023 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting. All rights reserved. Keywords: Diffuse large B cell lymphoma, Clinical trial