MK-2140-006 - A Multicenter, Open-label, Phase 2 Basket Study to Evaluate the Safety and Efficacy of MK-2140 as a Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies.

Studio Clinico

Patologia: Linfomi, Neoplasie ematologiche

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: II Randomizzato

Linee di trattamento: Seconda linea, Terza/N linea

Criteri di inclusione: 

For aggressive B-cell malignancies MCL:
- Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease after at least 2 prior systemic therapies including a Bruton's tyrosine kinase inhibition/inhibitor(s) (BTKi), and is post chimeric antigen receptor T (CAR-T) cell therapy or is ineligible for CAR-T cell therapy.
For aggressive B-cell malignancies MCL Cohort C:
- Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease after at least 1 prior systemic therapy and has no prior exposure to a non-covalent BTKi.
For aggressive B-cell malignancies Richter transformation lymphoma (RTL):
- Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease.
For indolent B-cell malignancies FL and CLL:
- Has histologically confirmed biopsy and has relapsed or refractory disease after at least 2 prior systemic therapies and no other available therapy.
- Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization/allocation.
- Have an ECOG performance status of 0 to 2 assessed within 7 days before cycle 1 day 1.

Criteri di esclusione: 

- Has received solid organ transplant at any time.
- 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 (<6 months prior to enrollment), 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.
- Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
- Participants with FL who have transformed to a more aggressive type of lymphoma.
- Has received prior systemic anticancer therapy within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibodies) or 2 weeks (if prior therapy was small molecules like kinase inhibitors) prior to the first dose of study intervention.
- Has received prior radiotherapy within 28 days of start of study intervention. Participants must have recovered from all radiation-related toxicities.
- 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 known active central nervous system (CNS) lymphoma involvement or active CNS involvement by lymphoma.
- Has an active infection requiring systemic therapy.
- Has a known history of human immunodeficiency virus (HIV) infection.
- Active HBV or hepatitis C virus (HCV) infection.
- For Cohort C only: has any clinically significant gastrointestinal abnormalities that might alter absorption.

Trattamento sperimentale: 

BIOLOGICAL: Zilovertamab vedotin
DRUG: Nemtabrutinib

Trattamento di controllo: 

-

Centri partecipanti

Nord Italia

Centro Italia

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2021-004450-36

Data di inserimento: 16.11.2023

Data di aggiornamento: 23.09.2024

Promotore

Merck Sharp & Dohme LLC

Principal Investigator ITALIA

Istituto Clinico Humanitas - Rozzano

Riferimento: Prof. Armando Santoro

Telefono: 0282244080

Email: armando.santoro@cancercenter.humanitas.it

Localita: Rozzano (MI)