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MK-1026-003 - A Phase 2 Study to Evaluate the Efficacy and Safety of MK-1026 in Participants With Hematologic Malignancies

Studio Clinico

Patologia: Neoplasie ematologiche

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: No

Fase di studio: II

Linee di trattamento: Seconda linea, Terza/N linea

Criteri di inclusione: 

  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days prior to allocation
  • Has a life expectancy of at least 3 months, based on the investigator assessment
  • Has the ability to swallow and retain oral medication
  • 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
  • Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening
  • Has adequate organ function
  • Male participants agree to refrain from donating sperm and agree to either remain abstinent from heterosexual intercourse as their preferred and usual lifestyle OR agree to use contraception, during the intervention period and for 12 days after last dose of study intervention
  • Female participants not pregnant or breastfeeding are eligible to participate if not a woman of childbearing potential (WOCBP), or if a WOCBP they either use a contraceptive method that is highly effective OR remain abstinent from heterosexual intercourse as their preferred and usual lifestyle during the intervention period and for at least 30 days after the last dose of study intervention

Part 1 and Part 2 (Cohorts A to C and Cohort I):

  • Has a confirmed diagnosis of CLL/SLL
  • Has active disease for CLL/SLL clearly documented to initiate therapy
  • Has evaluable core or excisional lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy at Screening (optional for participants enrolling in Part 1)

Part 2 (Cohorts D to G):

  • Has a confirmed diagnosis of and response to previous treatment of one of the following:
  • Participants with Richter's transformation who are relapsed or refractory following at least 1 line of prior therapy (Cohort D)
  • Participants with pathologically confirmed MCL, documented by either overexpression of cyclin D1 or t(11;14), who are relapsed or are refractory to chemoimmunotherapy and a covalent irreversible BTK inhibitor (BTKi) (Cohort E)
  • Participants with MZL (including splenic, nodal, and extra nodal MZL) who are relapsed or refractory to chemoimmunotherapy and a covalent irreversible BTKi (Cohort F)
  • Participants with FL who are relapsed or refractory to chemoimmunotherapy, immunomodulatory agents (i.e. lenalidomide plus rituximab) (Cohort G)
  • Have measurable disease defined as at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan
  • Has a lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy at Screening

Part 2 (Cohort H):

  • Confirmed diagnosis of WM; participants who are relapsed or refractory to standard therapies for WM including chemoimmunotherapy and a covalent irreversible BTKi
  • Has active disease defined as 1 of the following: systemic symptoms, physical findings, laboratory abnormalities, coexisting disease
  • Has measurable disease, satisfying any of the following: at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan (minimum measurement must be >15 mm in the longest diameter or >10 mm in the short axis); IgM ≥4500 g/dL; or bone marrow infiltration of 70%
  • Has fresh bone marrow aspirate for biomarker analysis at Screening

Criteri di esclusione: 

  • Active HBV/HCV infection
  • History of malignancies < 3 years
  • Active CNS disease
  • Active infections requiring systemic Therapy
  • HIV infection known history
  • Received prior systemic anticancer therapy < 4 weeks prior to llocation
  • Currently participating in or has participated in a study with investigational agent

Schema di trattamento: 

Participants receive nemtabrutinib tablets orally once daily (QD) until progressive disease (PD) or discontinuation (single group, open label)

Trattamento sperimentale: 

Nemtabrutinib (MK1026)

Trattamento di controllo: 

NA

Obiettivi primari dello studio: 

The purpose of this study is to evaluate the safety and efficacy of nemtabrutinib (formerly ARQ 531) in participants with hematologic malignancies of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Richter's transformation, marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and Waldenström's macroglobulinemia (WM). This study will be conducted in 2 parts: dose escalation and confirmation (part 1) and cohort expansion (part 2). Following determination of RP2D in Part 1, the study will proceed with Part 2 using 8 disease specific expansion cohorts (A-H). The primary endpoints of Part 1 of the study are to evaluate the DLTs, AEs, and AEs related resulting in treatment discontinuation with the aim to establish a RP2D of MK1026 for Part 2. Part 2 primary objectives: ORR per iWCLL, ORR per Lugano, ORR per iWWM as assesses by ICR.

Obiettivi secondari dello studio: 

Approximately 466 participants will be enrolled in Part 2: a target of 60 participants in each for Cohort A and E-H; 40 participants in each of Cohorts B, C, and D; and 46 in Cohort I. Participants will be enrolled within disease-specific cohorts. Part 2 primary objectives: PK, DOR, safety.

Data di inizio dell'arruolamento: 01.04.2021

Data di fine dell'arruolamento: 31.03.2025

Centri partecipanti

Nord Italia

Ospedale S.Orsola Malpighi, Università di Bologna
Via Pietro Albertoni 15 - 40138 Bologna - BO
Ematologia

Riferimento: Prof. Pierluigi Zinzani
Telefono: 0512143680
Email: pierluigi.zinzani@unibo.it

 

Ospedale San Raffaele di Milano
Via Olgettina 60 - 20132 Milano - MI

 

Sud Italia e isole

Istituto Nazionale Tumori IRCCS Fondazione Pascale
Via Mariano Semmola - 80131 Napoli - NA
N.B.: Arruolamento pazienti non ancora attivo

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2020-002324-36

Data di inserimento: 24.05.2022

Promotore

Merck Sharp & Dohme LLC

Principal Investigator ITALIA

Ospedale Sant'Orsola Malpighi, Università di Bologna (Ematologia)

Riferimento: Prof. Pierluigi Zinzani

Telefono: 0512143680

Email: pierluigi.zinzani@unibo.it

Localita: Bologna

 

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