zilovertamab vedotin (MK-2140) / Merck (MSD) - LARVOL DELTA

Phase 2 trial of zilovertamab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone plus rituximab in diffuse large B-cell lymphoma: Updated analysis of waveline-007 (ASH 2025) - P2 | "After approximately 27 months of follow-up, ZV plus R-CHP continues to demonstraterobust efficacy and acceptable safety as front-line treatment for participants with DLBCL regardless ofcell of origin. No new safety concerns were reported."

Combination therapy • P2 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • ROR1

Zilovertamab vedotin plus R-CHP versus polatuzumab vedotin plus R-CHP as first-line therapy in participants with germinal center B-cell diffuse large B-cell lymphoma (DLBCL): The randomized, open-label, Phase 2 waveline-011 Study (ASH 2025) - P2 | "Polatuzumab vedotin in combination with rituximab, cyclophosphamide, doxorubicin, andprednisone (R-CHP) is a standard-of-care option for the first-line treatment of DLBCL, regardless ofsubtype. Approximately 594participants with GCB DLBCL will be enrolled. Recruitment for waveLINE-011 is currently underway."

Clinical • P2 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Mediastinal B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Primary Mediastinal Large B-Cell Lymphoma • Respiratory Diseases • Solid Tumor • ROR1

Zilovertamab vedotin plus R-CHP versus R-CHOP for first-line treatment of diffuse large B-cell lymphoma: The phase 3 waveline-010 study (ASH 2025) - P3 | "The current standard of care forpreviously untreated DLBCL is rituximab plus cyclophosphamide, doxorubicin, vincristine, andprednisone (R-CHOP). Zilovertamab vedotin is an ROR1-targeting antibody-drug conjugate with amonomethyl auristatin E payload that has shown encouraging antitumor activity in patients with DLBCL.The waveLINE-010 study (NCT06717347) is a randomized, open-label, phase 3 study designed to assessthe efficacy and safety of zilovertamab vedotin in combination with rituximab plus cyclophosphamide,vincristine, and prednisone (R-CHP) versus R-CHOP in participants with previously untreated DLBCL...Reused with permission. This Abstract was acceptedand previously presented at the 2025 ASCO Annual Meeting."

Clinical • P3 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Epstein-Barr Virus Infections • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • ROR1

Phase 2/3 trial of zilovertamab vedotin plus standard of care in relapsed/ refractory diffuse large B-cell lymphoma: Updated analysis of waveline-003 (ASH 2025) - P2/3 | "The phase 2/3 waveLINE-003 trial (NCT05139017) evaluated the safety and efficacy of ZV plusrituximab and gemcitabine-oxaliplatin (R-GemOx) in participants with R/R DLBCL...The median number of prior therapies was 2.0 with 7 (18%) pts receiving prior CAR-T, 7 (18%)receiving prior ASCT, and 2 (5%) received prior polatuzumab vedotin... After approximately 19 months of follow-up, ZV plus R-GemOX continues to demonstratepromising efficacy and acceptable safety in R/R DLBCL at the RP2D of ZV of 1.75 mg/kg plus R-GemOx. Nonew safety concerns were reported. The efficacy expansion phase of this trial randomizing participants toZV plus R-GemOx versus R-GemOx is currently ongoing."

P2/3 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Septic Shock • ROR1

Trial-in-Progress: A Phase 1/2 Multi-Center Study of Onct-808, a ROR1-Specific CAR T, in Adult Patients with Relapsed/Refractory Aggressive B Cell Lymphoma (ASH 2023) - P1/2 | "Zilovertamab vedotin showed preliminary evidence of efficacy and no evidence of on-target off-tumor toxicity in patients with advanced B cell malignancies (Wang 2022)...Subjects will receive a conditioning regimen of intravenous (IV) cyclophosphamide and fludarabine, followed by ONCT-808 IV infusion...The trial is currently active and patients have been treated in the phase 1 dose escalation. Clinical Trial Identifier: NCT05588440"

Clinical • IO biomarker • P1/2 data • B Cell Lymphoma • Bone Marrow Transplantation • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ROR1

Zilovertamab Vedotin (MK-2140) in Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL): Updated Results from the Phase 2 Waveline-004 Study (ASH 2023) - P2 | "In this updated analysis of waveLINE-004, zilovertamab vedotin continued to demonstrate clinically meaningful antitumor activity in pts with R/R DLBCL who had progressed after or were ineligible for ASCT and/or CAR T-cell therapy. The safety profile of zilovertamab vedotin was manageable, and consistent with the known profile of MMAE-containing agents."

P2 data • Acute Kidney Injury • Anemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Metabolic Disorders • Nephrology • Non-Hodgkin’s Lymphoma • Oncology • Renal Disease • Septic Shock • ROR1

Zilovertamab Vedotin Monotherapy for Patients with Relapsed or Refractory Mantle Cell Lymphoma: Cohort a of the Multicenter, Open-Label, Phase 2 Waveline-006 Study (ASH 2024) - P2 | "The phase 2, multicohort, waveLINE-006 study (NCT05458297) was designed to assess the efficacy and safety of zilovertamab vedotin as monotherapy and in combination with the BTKi nemtabrutinib in R/R aggressive and indolent B-cell malignancies. Conclusions : Zilovertamab vedotin monotherapy demonstrated antitumor activity and manageable safety in heavily pretreated pts with R/R MCL in cohort A of waveLINE-006. Further investigation is warranted to better understand the efficacy of zilovertamab vedotin for R/R MCL."

Clinical • Monotherapy • P2 data • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • ROR1 • TP53

Zilovertamab Vedotin in Combination with Nemtabrutinib for Patients with Relapsed or Refractory Mantle Cell Lymphoma: Cohort C of the Open-Label, Phase 2 Waveline-006 Study (ASH 2024) - P2 | "Further investigation into efficacy of this combination is warranted for pts with R/R MCL. The study is ongoing and the RP2D is yet to be determined."

Clinical • Combination therapy • P2 data • Fatigue • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Oncology • ROR1 • TP53

Updated Results from the Phase 2 Waveline-004 Study of Zilovertamab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma (ASH 2024) - P2 | "Summary/Conclusion : After additional follow-up, zilovertamab vedotin continued to demonstrate sustained antitumor activity and manageable safety in patients with R/R DLBCL whose disease progressed after or were ineligible for ASCT and/or CAR-T therapy. These results support the continued investigation of zilovertamab vedotin in patients with R/R DLBCL."

P2 data • Acute Kidney Injury • Anemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Metabolic Disorders • Nephrology • Non-Hodgkin’s Lymphoma • Oncology • Renal Disease • Septic Shock • ROR1

A Phase 1/2 Study of a ROR1-Targeting CAR T Cell Therapy (ONCT-808) in Adult Patients with Relapsed/Refractory (R/R) Aggressive B Cell Lymphomas (BCL) (ASH 2024) - P1/2 | "ONCT-808 utilizes a ROR1-binding moiety derived from zilovertamab, which, in a prior study of zilovertamab vedotin, demonstrated antitumor activity and no evidence of off-tumor toxicity in a population of heavily pretreated patients (pts) with aggressive lymphoma (Wang 2022, Spurgeon 2023)...ONCT-808 is administered as a single infusion following lymphodepletion with fludarabine and cyclophosphamide...Preliminary PK demonstrates successful expansion and persistence of ROR1-positive CAR T cells, including beyond 12 months post-infusion.CONCLUSIONS : ONCT-808 is a novel ROR1-targeting CAR T therapy with promising early activity and appears to be well-tolerated at 0.3 x 106 and 1 x 106 viable cells/kg dose in patients with R/R BCL. Dose escalation continues towards optimizing activity and safety (NCT 05588440)."

CAR T-Cell Therapy • Clinical • P1/2 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • ROR1

Waveline-007: Dose Escalation and Confirmation, and Efficacy Expansion Trial of Zilovertamab Vedotin in Combination with Cyclophosphamide, Doxorubicin, and Prednisone Plus Rituximab in Patients with Diffuse Large B Cell Lymphoma (ASH 2024) - P2 | "The recommended Phase 2 dose (RP2D) of ZV was established at 1.75 mg/kg and the combination therapy at this dose level achieved objective response rate and complete response rate at end of treatment of 100%. The combination provided a robust response in patients with DLBCL and warrants further evaluation in a larger population."

Clinical • Combination therapy • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Respiratory Diseases • ROR1

Next Questions: Mantle Cell Lymphoma (SOHO 2025) - "Glofitamab is being evaluated in a phase 3 randomized clinical trial (GLOBRYTE) in patients with MCL who have relapsed following BTKi therapy, 7 which may prove to be an excellent option in this population...The combination of mosunetuzumab with the ADC polatuzumab vedotin (M-Pola) was evaluated in a phase 1b/2 study, with an ORR of 75% (15/20) and CRR of 70% (14/20)...The receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal protein that is present in MCL, and the ADC zilovertamab vedotin recognizes ROR1 and delivers the anti-microtubule cytotoxin monomethyl auristatin E. In a phase 1 study that included patients with MCL, the ORR was 47% (7/15). 12 Loncastuximab tesirine is an ADC containing a CD19 monoclonal antibody conjugated to a pyrrolobenzodiazepine dimer toxin...Novel immunomodulatory agents (ie, golcadomide) are being evaluated in both FL and DLBCL and currently demonstrate favorable outcome — especially in combination with rituximab. 16, 17..."

B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Oncology • Waldenstrom Macroglobulinemia • CD20 • CRBN • ROR1

Ongoing Phase 3 waveLINE-010 Study of Zilovertamab Vedotin (ZV) Plus R-CHP Versus R-CHOP in Participants With Untreated Diffuse Large B-Cell Lymphoma (DLBCL) (SOHO 2025) - P3 | "Design: waveLINE-010 is a randomized, open-label, phase 3 study designed to evaluate ZV in combination with rituximab plus cyclophosphamide, doxorubicin, and prednisone (R-CHP) versus rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in untreated DLBCL. Reused with permission. This abstract was accepted and previously presented at the 2025 ASCO Annual Meeting."

P3 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ROR1

Phase 2 Study of Zilovertamab Vedotin in Participants With Metastatic Solid Tumors. (PubMed, Cancer Res Commun) - P2 | "Zilovertamab vedotin had minimal antitumor activity, with only a single responder, and manageable safety in participants with previously-treated metastatic solid tumors."

Journal • P2 data • Platinum resistant • Breast Cancer • Fatigue • Hematological Malignancies • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Lymphoma • Non Small Cell Lung Cancer • Non-Hodgkin’s Lymphoma • Oncology • Ovarian Cancer • Pain • Pancreatic Cancer • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • HER-2 • ROR1

waveLINE-006: A Study of Zilovertamab Vedotin (MK-2140) as Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (MK-2140-006) (clinicaltrials.gov) - P2 | N=223 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial primary completion date: Mar 2027 ➔ Mar 2029

Monotherapy • Pan tumor • Trial primary completion date • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Mantle Cell Lymphoma • Oncology • Richter's Syndrome

waveLINE-004: A Study to Evaluate Zilovertamab Vedotin (MK-2140) for Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) (MK-2140-004) (clinicaltrials.gov) - P2 | N=140 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Jun 2025 ➔ Jan 2026 | Trial primary completion date: Jun 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

PHASE 2/3 waveLINE-003 STUDY: ZILOVERTAMAB VEDOTIN PLUS STANDARD OF CARE IN RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA (ICML 2025) - P2/3 | "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. 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."

P2/3 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ROR1

KEYMAKER-U04 substudy 04A: A Substudy of Investigational Agents in Programmed Cell Death-1/Ligand 1 (PD-1/L1) Refractory Locally Advanced or Metastatic Urothelial Carcinoma (mUC) (MK-3475-04A) (clinicaltrials.gov) - P1/2 | N=48 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial completion date: Oct 2027 ➔ May 2028 | Trial primary completion date: Oct 2027 ➔ May 2028

Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Urothelial Cancer

ZILOVERTAMAB VEDOTIN PLUS STANDARD OF CARE IN RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: RESULTS FROM THE PHASE 2/3 WAVELINE-003 STUDY (EHA 2025) - P2/3 | "Zilovertamab vedotin (ZV) is a novel ROR1-targeting antibody-drug conjugate that has shown promising efficacy in patients with DLBCL.Aims: We present results of the dose confirmation phase of the waveLINE-003 (NCT05139017) study evaluating ZV plus rituximab and gemcitabine-oxaliplatin (R-GemOx) in participants with R/R DLBCL.Eligible participants were aged ≥18 years with confirmed R/R DLBCL who 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) and have failed ≥1 line of prior therapy. In participants with R/R DLBCL, ZV in combination with R-GemOx showed promising efficacy and a manageable safety profile at the RP2D of ZV at 1.75 mg/kg. Evaluation of ZV–R-GemOx versus R-GemOx is proceeding to the randomized phase 3 portion of the study"

P2/3 data • Anemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • Septic Shock • ROR1

WaveLINE-003: Phase 2/3 trial of zilovertamab vedotin plus standard of care in relapsed/refractory diffuse large B-cell lymphoma. (ASCO 2025) - P2/3 | "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. 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."

P2/3 data • Anemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • Septic Shock • ROR1

waveLINE-010: Zilovertamab vedotin plus R-CHP versus R-CHOP in untreated diffuse large B-cell lymphoma. (ASCO 2025) - P3 | "Modest improvements have been made over standard-of-care with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) immunochemotherapy being used in the first-line setting. Adverse events will be graded per NCI CTCAE v5.0. Recruitment is ongoing."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Epstein-Barr Virus Infections • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ROR1

Phase 1/2 study of zilovertamab vedotin in pediatric and young adult hematologic malignancies or solid tumors (LIGHTBEAM-U01A). (ASCO 2025) - P1/2 | "Approximately 50-90 pts will be enrolled. Recruitment is underway."

Clinical • P1/2 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Lymphoma • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Ewing Sarcoma • Hematological Malignancies • Leukemia • Lymphoma • Neuroblastoma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • Sarcoma • Solid Tumor • ROR1

Research on Novel Treatment Approaches and Scientific Advances From Merck’s Broad and Differentiated Oncology Portfolio and Pipeline to be Presented at ASCO 2025 (Merck (MSD) Press Release) - "New and updated data for MK-1084, an investigational KRAS G12C inhibitor, from the colorectal cancer and non-small cell lung cancer cohorts of the Phase 1 KANDLELIT-001 study will be presented; Zilovertamab vedotin and sacituzumab tirumotecan data to highlight progress in Merck’s pipeline of innovative antibody-drug conjugates; Follow-up data for KEYTRUDA (pembrolizumab) and WELIREG (belzutifan), as well as new and updated analyses for KEYTRUDA in earlier stages of cancer, add to the body of evidence supporting the role of these medicines."

Clinical data • Cervical Cancer • Clear Cell Renal Cell Carcinoma • Colorectal Cancer • Diffuse Large B Cell Lymphoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Melanoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Prostate Cancer • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Von Hippel-Lindau Syndrome

Merck’s Investigational Zilovertamab Vedotin at 1.75 mg/kg Dose Plus Standard of Care Showed Promising Antitumor Activity, Including Complete Response Rate, in Patients With Relapsed/Refractory DLBCL in Phase 2 Portion of waveLINE-003 Trial (Merck (MSD) Press Release) - P2/3 | N=290 | waveLINE-003 (NCT05139017) | Sponsor: Merck Sharp & Dohme LLC | "At a pre-planned analysis, zilovertamab vedotin 1.75 mg/kg in combination with R-GemOx achieved a 56.3% objective response rate (ORR) in patients with relapsed or refractory DLBCL (n=16), with eight complete responses (CR) and one partial response (PR). These data are being presented for the first time today during an oral presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #7005)...Treatment-related adverse events (TRAEs) were reported in 98% of patients (n=40)....The median follow-up for all participants was 9.8 months. At a median follow-up of 18.1 months (range, 2.4 to 23.3 months) in patients receiving the 1.5 mg/kg dose of zilovertamab vedotin (n=15), ORR was 26.7% (3 CR [20.0%], 1 PR [6.7%]) and median DOR was 14.4 months (95% CI, not reached [NR]-NR)."

P2 data • Diffuse Large B Cell Lymphoma

waveLINE-010: A Study to Evaluate Zilovertamab Vedotin (MK-2140) Combination With Rituximab Plus Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Participants With Previously Untreated DLBCL (MK-2140-010) (clinicaltrials.gov) - P3 | N=1046 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Trial primary completion date: Mar 2032 ➔ Jul 2029

Trial primary completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology