Zilovertamab Vedotin (MK‐2140) in Relapsed or Refractory (R/R) Non‐hodgkin Lymphoma (NHL): 14‐month Follow‐up of the Phase 1 Waveline‐001 Study

Introduction: The ROR1-targeting antibody-drug conjugate zilovertamab vedotin (ZV) had a manageable safety profile and promising antitumor activity in patients (pts) with R/R NHL in the phase 1 waveLINE-001 study (NCT03833180). We present updated results after 14 months of follow-up for pts with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and Richter transformation (RT). Methods: Eligible pts were ≥18 y; had a histologic diagnosis of NHL and an ECOG PS of 0–2. Pts must have had disease progression during or relapse after prior systemic therapy. waveLINE-001 includes 3 dosing schedules; schedule 1 data are presented. Pts received ZV IV at a starting dose of 0.5 mg/kg Q3W increasing to 2.5 mg/kg using an accelerated 3 + 3 dose escalation. Primary end point was MTD and/or the recommended dosing regimen (RDR). Safety, ORR, DOR, PFS, and OS were secondary. Results: 56 pts were enrolled in schedule 1, of whom 30 received ZV at the previously established RDR (2.5 mg/kg). Median follow-up at data cutoff (Nov 27, 2022) was 14.3 mo (range, 0.5–44.2). Median age was 70.0 y, 59% of pts were male, 48% had an ECOG PS of 0. Pts with DLBCL (n = 17) received a median (range) of 4 (1–9) prior lines of therapy, 71% received prior CAR-T or CAR-NK and 47% had germinal center B cell–like subtype. Pts with MCL (n = 17) received a median (range) of 4 (1–9) prior lines of therapy and none received prior CAR-T or CAR-NK. 71% of MCL pts were Ann Arbor stage IV and 53% had mutated TP53. Pts with RT (n = 7) received a median (range) of 6 (1–10) prior therapies, and all had the DLBCL subtype. Any-cause AEs occurred in 54 pts (96%). Treatment-related AEs occurred in 41 pts (73%). Grade 3/4 treatment-related AEs occurred in 27 pts (48%), most frequently (≥10%) neutrophil count decreased (32%) and platelet count decreased (11%). No pts died because of a treatment-related AE. Peripheral neuropathy occurred in 27 pts (48%). No infusion-related reactions or tumor lysis syndrome occurred. Any-cause AEs led to discontinuation of ZV in 12 pts (21%) and interruption or reduction of ZV in 24 (43%). ORR was 29%, 53%, and 57% for pts with DLBCL, MCL, and RT respectively. ORR (95% CI) for pts with MCL and mutated TP53 was 44% (14–79). Additional efficacy results are in the table.. Conclusion: After 14 months of follow-up, ZV had a manageable safety profile and promising antitumor activity in pts with heavily pretreated DLBCL, MCL, and RT. These results are consistent with prior findings of waveLINE-001 and support continued investigation of ZV in NHL. The research was funded by: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA Keywords: Aggressive B-cell non-Hodgkin lymphoma, Chronic Lymphocytic Leukemia (CLL), Molecular Targeted Therapies Conflicts of interests pertinent to the abstract. M. L. Wang Consultant or advisory role: AbbVie, Acerta Pharma, ADC Therapeutics America, Amphista Therapeutics Limited, AstraZeneca, Be Biopharma, BeiGene, BioInvent, Deciphera, DTRM Biopharma (Cayman) Limited, Genentech, InnoCare, Janssen, Kite Pharma, Leukemia & Lymphoma Society, Lilly, Merck, Miltenyi Biomedicine, Milken Institute, Oncternal, Parexel, Pepromene Bio, Pharmacyclics, VelosBio Honoraria: AbbVie, Acerta Pharma, AstraZeneca, Bantam Pharmaceutical, BeiGene, BioInvent, Bristol Myers Squibb, CAhon, Dava Oncology, Eastern Virginia Medical School, Genmab, i3Health, IDEOlogy Health, Janssen, Kite Pharma, Leukemia & Lymphoma Society, Medscape, Meeting Minds Experts, MD Education, MJH Life Sciences, Merck, Moffit Cancer Center, Nurix, Oncology Specialty Group, OncLive, Pharmacyclics, Physicians Education Resources (PER), Practice Point Communications (PPC), Studio ER Congressi Research funding: Acerta Pharma, AstraZeneca, BeiGene, BioInvent, Celgene, Genmab, Genentech, Innocare, Janssen, Juno Therapeutics, Kite Pharma, Lilly, Loxo Oncology, Molecular Templates, Oncternal, Pharmacyclics, VelosBio, Vincerx M. Mei Consultant or advisory role: Novartis Honoraria: CTI, EUSA Research funding: Celgene, Beigene, Incyte/Morphosys Other remuneration: Speaker Bureau--Morphosys, Seagen P. M. Barr Consultant or advisory role: AbbVie/PCYC, Beigene, Gilead, BMS/Celgene, AstraZeneca, TG, Janssen, Regeneron, Seattle Genetics, Merck, Morphosys, Adaptive J. C. Barrientos Consultant or advisory role: Beigene, AstraZeneca, Pharmacyclics/AbbVie Research funding: Merck, Oncternal, Pharmacyclics/AbbVie R. R. Furman Consultant or advisory role: AbbVie, AstraZeneca, Beigene, Genentech, Incyte, Janssen, Loxo Pharmaceuticals, Morphosys, Pharmacyclics, TG Therapeutics, Sanofi, X4 Pharmaceuticals, MEI Pharma Honoraria: AstraZeneca K. Patel Consultant or advisory role: ADC Therapeutics, AbbVie, AstraZeneca, Caribou, Epizyme, Fate Therapeutics, Genentech, Lilly, MEI, Merck, Morphosys Pharmacyclics/Janssen, Xencor Research funding: Institutional--AbbVie, AstraZeneca, CRISPR, Curis Epizyme, Fate Therapeutics, Genentech/Roche, Lilly, MEI, Merck, NURIX, Pharmacyclics/Janssen, Xencor Other remuneration: Speaker Bureau--AstraZeneca, Kite, BMS W. G. Wierda Research funding: GSK/Novartis, Abbvie, Genentech, Pharmacyclics LLC, AstraZeneca/Acerta Pharma, Gilead Sciences, Bristol Myers Squibb (Juno & Celgene), KITE Pharma, Oncternal Therapeutics, Inc., Cyclacel, Loxo Oncology, Inc./Lilly, Janssen, Xencor Other remuneration: Chair of the CLL National Comprehensive Cancer Network Panel M. Y. Choi Research funding: Institution--AbbVie, TG Therapeutics, Geron, Merck, Oncternal, Pharmacyclics S. Wang Employment or leadership position: Merck & Co., Inc. Stock ownership: Merck & Co., Inc. U. C. Ogbu Employment or leadership position: Merck & Co., Inc. Stock ownership: Merck & Co., Inc., Roche P. Marinello Employment or leadership position: Merck Stock ownership: Merck S. E. Spurgeon Consultant or advisory role: Velos Bio, Karyopharm, Genentech, Janssen, Pharmacyclics Research funding: (Institution) Acerta Pharma, AstraZeneca, BeiGene, Bristol Myers Squibb, Genentech, Gilead Sciences, Ionis, Janssen, and Velos Bio, Merck, Incyte Other remuneration: Data Safety Monitoring Board: Fred Hutchinson Cancer Research Center