Zilovertamab vedotin (MK 2140) in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): Early results from the phase 2 waveLINE-004 study.

person Muhit Ozcan Ankara University School of Medicine, Ankara, Turkey info_outline Muhit Ozcan, Seung Tae Lee, Felix Mensah, Dipenkumar Modi, Alexander Fossa, Won Seog Kim, Ewa Paszkiewicz-Kozik, Yazeed Sawalha, Ömür Gökmen Sevindik, Lalita Norasetthada, Armando Santoro, Kumudu Pathiraja, Samhita Chakraborty, Patricia Marinello, David Lavie

Authors person Muhit Ozcan Ankara University School of Medicine, Ankara, Turkey info_outline Muhit Ozcan, Seung Tae Lee, Felix Mensah, Dipenkumar Modi, Alexander Fossa, Won Seog Kim, Ewa Paszkiewicz-Kozik, Yazeed Sawalha, Ömür Gökmen Sevindik, Lalita Norasetthada, Armando Santoro, Kumudu Pathiraja, Samhita Chakraborty, Patricia Marinello, David Lavie Organizations Ankara University School of Medicine, Ankara, Turkey, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD, Indiana Blood and & Marrow Transplantation, Franciscan Health, Indianapolis, IN, Karmanos Cancer Institute, Detroit, MI, Oslo University Hospital, Oslo, Norway, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea, Maria Sklodowska-Curie National Institute of Oncology, Warsaw, Poland, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH, Istanbul Medipol University, International School of Medicine, Istanbul, Turkey, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand, Humanitas University, Pieve Emanuele, and IRCCS Humanitas Research Hospital, Humanitas Cancer Center, Milan, Italy, Merck & Co., Inc., Rahway, NJ, Hadassah Medical Center, Jerusalem, Israel Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA Background: Treatment options are limited for patients (pts) with R/R DLBCL who are not candidates for autologous stem cell transplant (ASCT). ROR1 is an oncofetal protein pathologically expressed in hematologic malignancies including DLBCL. In the phase 1 first-in-human study in hematologic malignancies (waveLINE-001), the ROR1-targeting antibody-drug conjugate zilovertamab vedotin (ZV) showed promising activity and manageable safety in R/R DLBCL. The single-arm, open-label, phase 2 waveLINE-004 study (NCT05144841) is designed to evaluate activity of ZV monotherapy in pts with R/R DLBCL. Early data are reported. Methods: Eligible pts were ≥18 y old, had histologically confirmed DLBCL by WHO classification, measurable disease per Lugano 2014 criteria, PET-positive disease, and ECOG PS of 0-2. Pts must have received ≥2 prior lines of therapy (including an alkylating agent, anthracycline, and an anti-CD20 antibody) with progression after or ineligibility for ASCT and CAR T-cell therapy. All pts received ZV 2.5 mg/kg IV Q3W until disease progression, unacceptable toxicity, or withdrawal. Primary end point was ORR per Lugano 2014 criteria. Safety and tolerability was a secondary end point. Safety was evaluated in all pts who received ≥1 dose of treatment; efficacy was reported for pts with ≥3 mo follow-up. Results: At data cutoff (Nov 16, 2022), 40 pts enrolled and received ≥1 dose of treatment; 23 (58%) had discontinued and 17 (43%) were ongoing. Median age was 68.0 y, 29 (73%) pts were male, 37 (93%) had an ECOG PS of 0 or 1, 24 (60%) had ≥3 prior lines of therapy, and 10 (25%) received prior ASCT. 11 (28%) pts received prior CAR-T. Median follow-up (range) was 2.6 mo (0.3-7.9) for all pts and 6.0 mo (3.0-7.9) for pts in the efficacy analysis (n = 20). ORR by investigator review was 30% (95% CI, 11.9-54.3), with 2 pts having a CR and 4 a PR; 5 pts had SD (DCR, 55% [95% CI, 31.5-76.9]). Treatment related AEs (TRAEs) occurred in 28 (70%) pts, most commonly (≥15%) diarrhea (9 [23%]), anemia (8 [20%]), neutropenia (7 [18%]), neutrophil count decreased (7 [18%]), and alopecia (6 [15%]). Grade 3/4 TRAEs occurred in 16 (40%) pts, most commonly (≥10%) neutropenia (7 [18%]), anemia (6 [15%]), and neutrophil count decreased (4 [10%]). Discontinuation due to a TRAE of diabetic ketoacidosis occurred in 1 (3%) pt. Grade 1/2 treatment-related peripheral neuropathy occurred in 6 (15%) pts; no grade 3/4 AEs occurred. Dose reduction due to treatment-related peripheral neuropathy occurred in 3 (8%) pts. No infusion reaction or tumor lysis syndrome due to treatment occurred and no pts died because of TRAEs. Conclusions: Early results show that ZV had clinically meaningful antitumor activity in pts with R/R DLBCL who progressed after or have been ineligible for ASCT and/or CAR-T. Additionally, the safety profile was manageable and consistent with other monomethyl auristatin E–containing agents. Clinical trial information: NCT05144841.

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