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

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

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

ALM-401: A first-in-class next generation bispecific ADC configured to deliver superior efficacy in selected solid tumor indications (AACR 2025) - "This bsADC significantly outperforms a zilovertamab vedotin biosimilar, which exhibits an ORR of 22% (2/9) in these models at the same payload equivalent dose. ALM-401 has excellent plasma stability, a PK profile in line with approved ADCs, and good overall manufacturing and developability characteristics, with the potential to deliver significantly improved patient outcomes across a range of solid tumor indications with high unmet need."

Clinical • Late-breaking abstract • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • ROR1

A Clinical Study of Zilovertamab Vedotin (MK-2140) Plus Rituximab Plus Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Polatuzumab Vedotin Plus R-CHP in People With Diffuse Large B-cell Lymphoma (DLBL) (MK-2140-011/waveLINE-011) (clinicaltrials.gov) - P2 | N=594 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) in BTKi-treated mantle cell lymphoma (AACR 2025) - P2 | "Here, we explored which biomarkers might be associated with resistance to acalabrutinib, a second generation BTKi, by analyzing samples from MCL patients who were on treatment or progressed on acalabrutinib from the ACE-LY-004 study (NCT02213926), as well as using a pre-clinical MCL cell line model...It was previously attributed to a bypass resistance mechanism to first generation BTKi ibrutinib (Zhang et al., 2019)...To assess potential therapeutic implications of decreased surface expression of ROR1 in MCL post BTKi treatment, we assessed activity of a ROR1-targeted ADC (Zilovertamab vedotin; Wang et al., 2021) in BTKi-R cells...These preliminary results highlight the possible association between ROR1 expression on MCL tumor cells and BTKi response. To further dissect the interplay between ROR1 and second generation/reversible BTKi treatment in MCL, studies utilizing a multi-omics integration approach, BTKi-R MCL cell lines, and ex vivo propagated MCL patient cell..."

B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD5 • ROR1

Zilovertamab vedotin in pediatric and young adult hematologic malignancies or solid tumors: Phase 1/2 LIGHTBEAM-U01A study (AACR 2025) - P1/2 | "Secondary end points include pharmacokinetics, immunogenicity, duration of response, and eligibility for transplant/CAR-T therapy in pts with B-ALL or DLBCL/Burkitt lymphoma. Recruitment is ongoing."

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

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 completion date: Apr 2027 ➔ May 2029

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

A Clinical Study of Zilovertamab Vedotin (MK-2140) Plus Rituximab Plus Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Polatuzumab Vedotin Plus R-CHP in People With Diffuse Large B-cell Lymphoma (DLBL) (MK-2140-011/waveLINE-011) (clinicaltrials.gov) - P2 | N=594 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

New P2 trial • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Zilovertamab Vedotin Produces Activity in Heavily Pretreated R/R Mantle Cell Lymphoma (OncLive) - P2 | N-223 | waveLINE-006 (NCT05458297) | Sponsor: Merck Sharp & Dohme LLC | "Treatment with the ROR1-targeted antibody-drug conjugate (ADC) zilovertamab vedotin (MK 2140) produced antitumor activity and displayed a manageable safety profile in heavily pretreated patients with relapsed/refractory mantle cell lymphoma (MCL), according to data from cohort A of the phase 2 waveLINE-006 trial (NCT05458297) presented at the 2024 ASH Annual Meeting. Findings showed that patients treated with the ADC (n = 40) achieved an overall response rate (ORR) of 40% (95% CI, 25%-57%), which included a complete response rate of 13% and a partial response rate of 28%. The rates of stable disease and progressive disease were 10% and 28%, respectively. One patient (3%) was not evaluable for response, and 20% of patients were not assessed for response."

P2 data • Mantle Cell Lymphoma

Merck Announces Phase 3 waveLINE-010 Trial Initiation Evaluating Zilovertamab Vedotin, an Investigational Antibody-Drug Conjugate, for the Treatment of Patients With Previously Untreated Diffuse Large B-Cell Lymphoma (Businesswire) - "Merck...today announced the initiation of waveLINE-010, a pivotal Phase 3 clinical trial evaluating zilovertamab vedotin in combination with rituximab plus cyclophosphamide, doxorubicin and prednisone (R-CHP) compared to rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) alone, for the treatment of patients with previously untreated diffuse large B-cell lymphoma (DLBCL)...Global recruitment of the waveLINE-010 trial has begun, with patients now enrolling."

Enrollment status • 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 | Not yet recruiting ➔ Recruiting

Enrollment open • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

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

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 • Bone Marrow Transplantation • Fatigue • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Oncology • Pain • ROR1 • TP53

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) - "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 Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • ROR1

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 • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Metabolic Disorders • Nephrology • Non-Hodgkin’s Lymphoma • Oncology • Pain • 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 • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Pain • ROR1 • TP53

Merck’s Investigational Zilovertamab Vedotin in Combination With R-CHP Demonstrates Complete Response Rate of 100% at 1.75 mg/kg Dose in Phase 2 Trial of Previously Untreated Patients With Diffuse Large B-Cell Lymphoma (Businesswire) - P2 | N=60 | WaveLINE-007 (NCT05406401) | Sponsor: Merck Sharp & Dohme LLC | "These data are being presented for the first time today in an oral presentation (Abstract #578) at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition....The efficacy results showed a CR was achieved in combination with R-CHP in 100% (n=15) of patients receiving the 1.75 mg/kg dose of zilovertamab vedotin (CI: 95%, 78.2-100.0), 93.3% (n=14) of patients receiving the 2.0 mg/kg dose (CI: 95%, 68.1-99.8) and 100% (n=6) of patients receiving the 2.25 mg/kg dose (CI: 95%, 54.1-100.0). The total CR rate at the end of treatment was 97.2% (CI: 95%, 85.5-99.9). The median follow-up for all patients was 17.6 months (range, 7.1-24.6). The ORR was 100% (CI: 95%, 78.2-100.0) for patients receiving the 1.75 mg/kg dose, 93.3% (CI: 95%, 68.1-99.8) for patients receiving the 2.0 mg/kg dose, and 100% (CI: 95%, 54.1-100.0) for patients receiving the 2.25 mg/kg dose, all in combination with R-CHP."

P2 data • Diffuse Large B Cell Lymphoma

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 | Not yet recruiting | Sponsor: Merck Sharp & Dohme LLC

Combination therapy • New P3 trial • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Merck Data at the ASH 2024 Annual Meeting Highlights Promising Hematology Pipeline With Diverse Range of Investigational Assets and Novel Modalities (Merck (MSD) Press Release) - "Merck...today announced that new data for approved and investigational medicines across multiple hematologic malignancies will be presented at the American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego from Dec. 7-10. Data being shared at the meeting will showcase the company’s continued progress in advancing clinical research for Merck’s expanding and diverse pipeline of investigational candidates, with more than 20 abstracts being presented."

Clinical data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Mantle Cell Lymphoma • Oncology