Clinical study of Zilovertamab Vedotin (MK-2140) plus R-CHP compared to R-CHOP in patients with diffuse large B-cell lymphoma (DLBCL)
Résumé de l'étude
In this study, patients with DLBCL will be included, who are at least 18 years old and have not previously received treatment for their disease. The aim of the study is to evaluate the efficacy and safety of Zilovertamab Vedotin (MK-2140) in combination with R-CHP compared to R-CHOP for the treatment of DLBCL. R-CHP corresponds to R-CHOP, the standard therapy for DLBCL, without the component, Vincristine. Zilovertamab Vedotin (MK-2140) is an experimental drug. It is an antibody-drug conjugate (ADC) consisting of a monoclonal antibody in combination with a toxin (MMAE). Antibodies are proteins produced by the immune system that help the body fight foreign substances such as bacteria or viruses but also tumors. Monoclonal antibodies bind to specific targets on the cells. MK-2140 binds to a target on certain cancer cells known as “receptor tyrosine kinase-like orphan receptor 1 (ROR1)”. Through this binding, the toxin (MMAE) can damage the cancer cells. Zilovertamab Vedotin (MK-2140) has shown promising results against DLBCL in previous clinical phase 2 studies and is therefore combined with R-CHP in this study. The total duration of the study is expected to be approximately 7.5 years and will include approximately 1046 patients worldwide, of which about 11 in Switzerland.
(BASEC)
Intervention étudiée
After thorough counseling, careful eligibility screening, and collection of medical history (taking up to 28 days), the patient will be included in the study and randomly assigned (1:1 ratio) to one of the two treatment groups.
Group 1: Patients receive Zilovertamab Vedotin (MK-2140) plus R-CHP
Group 2: Patients receive R-CHOP
The duration of the treatment phase is approximately 18 weeks and is divided into six 3-week cycles.
Zilovertamab Vedotin (MK-2140) and the medications that make up R-CHP and R-CHOP, except for prednisone, are administered via a needle in the arm. This is referred to as intravenous (i.v.) infusion. During the treatment phase, these medications are administered a total of 6 times every 3 weeks.
Prednisone is a tablet taken orally during the first 5 days of each cycle of the treatment phase.
Participants with high-risk DLBCL in both treatment groups may receive 2 additional cycles of rituximab. Rituximab is a component of R-CHP and R-CHOP. Thus, the duration of the treatment phase for these patients is approximately 24 weeks.
After the treatment phase or discontinuation of the study intervention, participants will continue to be monitored for disease progression and survival.
This study is referred to as a “non-blinded” study. This means that both the participants and the study physician and the sponsor know which group the patients have been assigned to and thus also which study medication they are receiving.
As part of study visits, various measures and examinations may be performed, e.g.: electrocardiogram (ECG), blood and urine tests, tumor biopsy sampling, radiological examinations (e.g., CT, PET, and MRI), assessment of general health status, and discussions with medical staff. The study team may also contact participants between visits and after the completion of the study drug intake to inquire about their health status.
(BASEC)
Maladie en cours d'investigation
Diffuse large B-cell lymphoma (DLBCL) is the most commonly diagnosed B-cell lymphoma in adults and accounts for about 30% of all cases of non-Hodgkin lymphoma (NHL) worldwide. Based on clinical and pathological features, DLBCL can be classified into different subgroups, with DLBCL, NOS (not otherwise specified) being the most common subtype. Despite the heterogeneity in morphology and clinical features, a combination therapy consisting of 5 different drugs (R-CHOP: rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) has remained the standard treatment approach for over two decades. Since the five-year survival rate for DLBCL patients is only between 60% and 80%, there is an urgent and unmet need in the first-line treatment of DLBCL.
(BASEC)
• Histologically confirmed diagnosis of DLBCL based on a prior biopsy • Evidence of PET-positive disease at the screening visit. This means that the patient receives a score of 4 to 5 on the 5-point Lugano scale. • No prior treatment for DLBCL. (BASEC)
Critères d'exclusion
• Change from an indolent (mild) disease to DLBCL (a more aggressive type) • Previous diagnosis of a type of lymphoma called PMBCL (primary mediastinal B-cell lymphoma) or a gray zone lymphoma • Diagnosis of a DLBCL classified as stage I according to the Ann-Arbor staging classification. (BASEC)
Lieu de l’étude
Bellinzona, St-Gall, Autre
(BASEC)
Baden
(BASEC)
Sponsor
Merck Sharp & Dohme LLC, Rahway, New Jersey, USA («MSD»), einer Tochtergesellschaft der Merck & Co., Inc., in der Schweiz vertreten durch MSD Merck Sharp & Dohme AG, Luzern
(BASEC)
Contact pour plus d'informations sur l'étude
Personne de contact en Suisse
Klaudia Georgi
+41 58 618 33 88
klaudia.georgi@cluttermsd.comMSD Merck Sharp & Dohme AG
(BASEC)
Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)
Commission cantonale d'éthique du Tessin
(BASEC)
Date d'approbation du comité d'éthique
16.01.2025
(BASEC)
Identifiant de l'essai ICTRP
NCT06717347 (ICTRP)
Titre officiel (approuvé par le comité d'éthique)
A Randomized, Open-Label, Multicenter, Phase 3 Study of Zilovertamab Vedotin (MK-2140) in Combination With R-CHP Versus R-CHOP in Participants With Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL) (waveLINE-010) (BASEC)
Titre académique
A Randomized, Open-Label, Multicenter, Phase 3 Study of Zilovertamab Vedotin (MK-2140) in Combination With R-CHP Versus R-CHOP in Participants With Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL) (waveLINE-010) (ICTRP)
Titre public
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) (ICTRP)
Maladie en cours d'investigation
Diffuse Large B-Cell Lymphoma (ICTRP)
Intervention étudiée
Biological: Zilovertamab vedotinBiological: RituximabDrug: CyclophosphamideDrug: DoxorubicinBiological: Rituximab BiosimilarDrug: PrednisoneDrug: PrednisoloneDrug: VincristineDrug: Rescue medication (ICTRP)
Type d'essai
Interventional (ICTRP)
Plan de l'étude
Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Critères d'inclusion/exclusion
Inclusion Criteria:
- Has histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL), by
prior biopsy, based on local testing according to the WHO classification of
neoplasms of the hematopoietic and lymphoid tissues
- Has positron emission tomography (PET) positive disease at screening, defined as 4
to 5 on the Lugano 5-point scale
- Has received no prior treatment for their DLBCL
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
assessed within 7 days before randomization
- Has an ejection fraction =45% as determined by either echocardiogram (ECHO) or
multigated acquisition (MUGA)
- Human immunodeficiency virus (HIV) infected participants must have well controlled
HIV on antiretroviral therapy (ART)
- Who are hepatitis B surface antigen (HBsAg) positive are eligible if they have
received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral
load prior to randomization
- Participants with history of hepatitis C virus (HCV) infection are eligible if HCV
viral load is undetectable at screening
Exclusion Criteria:
- Has a history of transformation of indolent disease to DLBCL
- Has received a diagnosis of primary mediastinal B-cell lymphoma (PMBCL) or Grey zone
lymphoma
- Has Ann Arbor Stage I DLBCL
- Has clinically significant (i.e., active) cardiovascular disease: cerebral vascular
accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months
prior to enrollment), unstable angina, congestive heart failure (New York Heart
Association Classification Class =II), or serious cardiac arrhythmia requiring
medication
- Has clinically significant pericardial or pleural effusion
- Has ongoing Grade >1 peripheral neuropathy
- Has a demyelinating form of Charcot-Marie-Tooth disease
- HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric
Castleman's Disease
- Has ongoing corticosteroid therapy
- Has received a live or live-attenuated vaccine within 30 days before the first dose
of study intervention. Administration of killed vaccines is allowed
- Known additional malignancy that is progressing or has required active treatment
within the past 2 years
- Known active central nervous system (CNS) lymphoma
- Has active autoimmune disease that has required systemic treatment in the past 2
years
- Has active infection requiring systemic therapy
- Has concurrent active HBV (defined as HBsAg positive and detectable HBV DNA) and HCV
(defined as anti-HCV antibody positive and detectable HCV ribonucleic acid (RNA))
infection
- Has history of allogeneic tissue/solid organ transplant (ICTRP)
non disponible
Critères d'évaluation principaux et secondaires
Progression-free survival (PFS) (ICTRP)
Complete Response at End of Treatment (CR at EOT);Overall Survival (OS);Event-free Survival (EFS);Duration of Complete Response (DurCR);Number of Participants Who Experience an Adverse Event (AE);Number of Participants Who Discontinue Study Treatment Due to an AE;Change From Baseline in Health-Related Quality Of Life (HRQoL) on Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) Trial Outcome Index (TOI) Score;Change From Baseline in HRQoL on FACT-Lym Total Score;Change From Baseline in HRQoL on FACT-Lym Physical Wellbeing (PWB) Score;Change From Baseline in HRQoL on Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) Neurotoxicity Subscale Score (ICTRP)
Date d'enregistrement
non disponible
Inclusion du premier participant
non disponible
Sponsors secondaires
non disponible
Contacts supplémentaires
Medical DirectorToll Free Number, Trialsites@msd.com, 1-888-577-8839, Merck Sharp & Dohme LLC (ICTRP)
ID secondaires
MK-2140-010, 2024-515566-13-00, U1111-1309-3971, jRCT2061240099, 2140-010 (ICTRP)
Résultats-Données individuelles des participants
non disponible
Informations complémentaires sur l'essai
https://clinicaltrials.gov/ct2/show/NCT06717347 (ICTRP)
Résultats de l'essai
Résumé des résultats
non disponible
Lien vers les résultats dans le registre primaire
non disponible