Clinical trial NCT05406401: A Study of Zilovertamab Vedotin (MK-2140) in Combination With Cyclophosphamide, Doxorubicin, and Prednisone Plus Rituximab or Rituximab Biosimilar (Truxima) (R-CHP) in Participants With Diffuse Large B-Cell Lymphoma (DLBCL) (MK-2140-007)
Official title: A Multicenter, Open-label, Phase 2 Dose Escalation and Confirmation, and Efficacy Expansion Study of Zilovertamab Vedotin (MK-2140) in Combination With R-CHP in Participants With DLBCL (waveLINE)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Lymphoma, Large B-Cell, Diffuse (DLBCL)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-06-06
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study consists of a dose escalation/confirmation phase and an efficacy expansion phase. The dose escalation/confirmation phase is to determine the safety and tolerability and establish a preliminary recommended Phase 2 dose (RP2D) of zilovertamab vedotin when administered in combination with R-CHP in participants with DLBCL who have received no prior treatment for their disease. The efficacy expansion phase is to determine the efficacy of the RP2D of zilovertamab vedotin when administered in combination with R-CHP in participants with DLBCL who have received no prior treatment for their disease.


Eligibility criteria: The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion:

* Has histologically confirmed diagnosis of DLBCL by prior biopsy
* Has PET-positive disease verified by blinded independent central review (BICR) at screening, defined as 4-5 on the Lugano response criteria 5-point scale
* Has received no prior treatment for DLBCL
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days prior to the start of study intervention

Exclusion:

* Has a history of transformation of indolent disease to DLBCL
* Has received solid organ transplant at any time
* Has received a diagnosis of primary mediastinal B-cell lymphoma (PMBCL)
* Has clinically significant (ie, 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 pericardial effusion or clinically significant pleural effusion
* Has ongoing Grade \>1 peripheral neuropathy
* Has a demyelinating form of Charcot-Marie-Tooth disease
* History of a second malignancy unless potentially curative treatment has been completed with no evidence of malignancy for 2 years with the exception of participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous-cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder
* Has received prior radiotherapy within 28 days of start of study intervention
* Has ongoing corticosteroid therapy (exceeding 30 mg daily of prednisone equivalent)
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
* Has received a strong inhibitor or inducer of CYP3A4 (including itraconazole, ketoconazole, posaconazole, or voriconazole) within 7 days prior to the start of study intervention or expected requirement for chronic use of a strong CYP3A4 inhibitor until \<30 days after the last dose
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 28 days before the first dose of study intervention
* Has known active central nervous system (CNS) lymphoma
* Has an active infection requiring systemic therapy
* Has a known history of human immunodeficiency virus (HIV) infection
* Has a known active hepatitis C virus infection
* Has a known active hepatitis B virus infection

Primary outcomes:
measure: Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) in Cycle 1
timeFrame: Cycle 1 (up to 21 days)
measure: Number of Participants Who Experienced At Least One AE
timeFrame: Up to approximately 8 months
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 5.5 months
measure: Complete Response Rate (CRR) per Lugano Response Criteria
timeFrame: Up to approximately 60 months
Secondary outcomes:
measure: Objective Response Rate (ORR) per Lugano Response Criteria
timeFrame: Up to approximately 60 months
measure: Duration of Response (DOR) per Lugano Response Criteria
timeFrame: Up to approximately 60 months
Other outcomes:
Locations:
city: Victoria
country: Canada
facility: BC Cancer Victoria-Clinical Trials Unit ( Site 0105)
state: British Columbia
city: Toronto
country: Canada
facility: William Osler Health System ( Site 0106)
state: Ontario
city: Montreal
country: Canada
facility: Hopital du Sacre-Coeur de Montreal ( Site 0108)
state: Quebec
city: Jerusalem
country: Israel
facility: Hadassah Medical Center ( Site 0401)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center-Hemato Oncology ( Site 0400)
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli-ISTITUTO DI EMATOLOGIA ( Site 0306)
state: Lazio
city: Milano
country: Italy
facility: Ospedale San Raffaele-Unità Linfomi ( Site 0305)
state: Lombardia
city: Palermo
country: Italy
facility: Az. Osp. Ospedali Riuniti VILLA SOFIA-CERVELLO-EMATOLOGIA I ( Site 0307)
state: Sicilia
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi-SOD Ematologia ( Site 0308)
state: Toscana
city: Alessandria
country: Italy
facility: Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare -Azienda Ospedaliera Nazionale SS. Ant
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 0201)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 0200)
city: Łódź
country: Poland
facility: Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumat-Oddiał Hematologii Ogólnej ( Site 0503)
state: Lodzkie
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Kilinka Onkologii I Hematologii ( Site
state: Mazowieckie
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 0504)
state: Pomorskie
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0505)
state: Slaskie
city: Sevilla
country: Spain
facility: HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO-Hematology ( Site 0704)
state: Andalucia
city: L'Hospitalet Del Llobregat
country: Spain
facility: Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 0703)
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz-Oncology & Hematology ( Site 0700)
city: Stanbul
country: Turkey
facility: Mega Medipol-Hematology ( Site 0808)
state: Istanbul
city: Ankara
country: Turkey
facility: Ankara Universitesi Tip Fakultesi Hastanesi-hematology ( Site 0801)
city: Edirne
country: Turkey
facility: Trakya University ( Site 0805)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: