Phase-2 study to assess the efficacy and safety of MK-1026 in participants with malignant hematological diseases.
Zusammenfassung der Studie
The study investigates the efficacy and safety of MK-1026, a BTK inhibitor, in adults with malignant hematological diseases. Approximately 486 patients are expected to participate in this study worldwide. Patients must have a relapse (disease progression after remission from the last therapy) or be refractory to an existing disease (no complete or partial response to the last therapy). B cells or B lymphocytes are a type of white blood cell whose main function in the immune system is to produce antibodies for immune defense. The malignant transformation of B cells and their precursors causes the diseases studied here. BTK is a molecule in the body that plays a key role in various biological processes such as cell growth, cell differentiation, metabolism, and apoptosis (programmed cell death). BTK also plays a very important role in B cell development. The investigational product in this study, MK-1026, contains a chemical active ingredient that inhibits this BTK molecule, thereby preventing B cell growth and survival and specifically targeting malignant cells. Significant progress has been made in recent years in exploring the complex mechanisms of action of BTK inhibition, and data are already available showing a response to BTK inhibitors in the B cell diseases studied here. Additionally, preliminary results suggest that MK-1026 is well tolerated in different malignant B cell diseases.
(BASEC)
Untersuchte Intervention
After careful eligibility assessment, collection of medical history, and detailed explanation, the participant will be included in the study.
This study is an open-label study, meaning that both the doctor and the participants themselves know which treatment they have been assigned.
All patients receive MK-1026. MK-1026 is a tablet and is taken once daily.
The treatment duration is up to 6.5 years, as long as safety is ensured and the medication shows effect. Participants will visit the study center approximately 26 times during the treatment period. During and after the treatment phase, health status will be regularly monitored for any progression of the cancer disease. In case of disease deterioration, patients will return to the study center for two additional safety follow-up visits. Subsequently, participants will be contacted by phone approximately every 12 weeks.
As part of the study appointments, various measures and examinations may take place, including: discussion of health status and current medication, inquiry about daily activities and any related limitations, administration/handing out of study medication, imaging procedures such as CT and/or MRI scans, cardiac examinations (electrocardiogram (ECG), samples of blood, urine, or tissue, physical examination including checking vital signs (pulse, blood pressure, etc.).
(BASEC)
Untersuchte Krankheit(en)
This study is aimed at male and female patients with a variety of hematological malignancies (cancers affecting the blood, bone marrow, and lymph nodes). Patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), Richter's transformation (RT), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and Waldenström's macroglobulinemia (WM) may be included. Patients must have a relapse (disease progression after remission from the last therapy) or be refractory to an existing disease (no complete or partial response to the last therapy). These diseases were selected for the study due to a significant medical need for effective and tolerable therapies, especially after the failure of first-line therapy. It cannot be guaranteed that participants in clinical trials will directly benefit from the treatment. Preliminary data already exist showing that BTK inhibitors, a special class of medications, have shown efficacy in these malignant hematological diseases. In recent years, treatments for malignant hematological diseases have shifted from chemotherapy to small molecular inhibitors such as BTK inhibitors.
(BASEC)
• Patients must have one of several different subtypes of a hematological disease specified in the protocol. • Patients must have a relapse (disease progression after remission from the last therapy) or be refractory to an existing disease (no complete or partial response to the last therapy). • Ability to swallow and retain oral medication. (BASEC)
Ausschlusskriterien
• An active HBV/HCV infection. • An active infection requiring systemic therapy. • An active CNS (central nervous system) disease. (BASEC)
Studienstandort
Bern, Lugano, Zürich
(BASEC)
Sponsor
MSD Merck Sharp & Dohme AG, Luzern
(BASEC)
Kontakt für weitere Auskünfte zur Studie
Kontaktperson Schweiz
Klaudia Georgi
+41 58 618 33 88,
klaudia.georgi@cluttermsd.comMSD Merck Sharp & Dohme AG, Luzern
(BASEC)
Wissenschaftliche Auskünfte
Merck Sharp & Dohme LLC,
1-888-577-8839
klaudia.georgi@cluttermsd.com(ICTRP)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Ethikkommission Zürich
(BASEC)
Datum der Bewilligung durch die Ethikkommission
05.04.2022
(BASEC)
ICTRP Studien-ID
NCT04728893 (ICTRP)
Offizieller Titel (Genehmigt von der Ethikkommission)
MK-1026-003: A Phase 2 Study to Evaluate the Efficacy and Safety of MK-1026 in Participants with Hematologic Malignancies (BASEC)
Wissenschaftlicher Titel
A Phase 2 Study to Evaluate the Efficacy and Safety of MK-1026 in Participants With Hematologic Malignancies (ICTRP)
Öffentlicher Titel
Efficacy and Safety of Nemtabrutinib (MK-1026) in Participants With Hematologic Malignancies (MK-1026-003) (ICTRP)
Untersuchte Krankheit(en)
Hematologic MalignanciesWaldenstroms MacroglobulinaemiaNon-Hodgkins LymphomaChronic Lymphocytic Leukaemia (ICTRP)
Untersuchte Intervention
Drug: Nemtabrutinib (ICTRP)
Studientyp
Interventional (ICTRP)
Studiendesign
Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Ein-/Ausschlusskriterien
Inclusion Criteria:
- 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 penile-vaginal intercourse as their preferred and usual lifestyle OR
agree to use contraception, during the intervention period and for at least the time
required to eliminate the study intervention after last dose of study intervention
- Female participants assigned female sex at birth who are not pregnant or
breastfeeding are eligible to participate if not a participant of childbearing
potential (POCBP), or if a POCBP they either use a contraceptive method that is
highly effective OR remain abstinent from penile-vaginal intercourse as their
preferred and usual lifestyle during the intervention period and for at least to
eliminate study intervention after the last dose of study intervention
- Participants with HIV are eligible if they meet all of the following: the CD4 count
is >350 cells/uL at screening, the HIV viral load is below the detectable level, are
on a stable ART regimen for at least 4 weeks prior to study entry, and are compliant
with their ART
Part 1 and Part 2 (Cohorts A to C and J)
- Has a confirmed diagnosis of CLL/SLL with
- At least 2 lines of prior therapy (Part 1 only)
- Part 2 Cohort A: CLL/SLL participants who are relapsed or refractory to prior
therapy with a covalent, irreversible Bruton's tyrosine kinase inhibitor
(BTKi), and a B-cell lymphoma 2 inhibitor (BCL2i). CLL participants must have
received and failed, been intolerant to, or determined by their treating
physician to be a poor phosphoinositide 3-kinase inhibitor (PI3Ki) candidate or
ineligible for a PI3Ki per local guidelines
- Part 2 Cohort B: CLL/SLL participants who are relapsed or refractory following
at least 1 line of prior therapy and are BTKi treatment naive
- Part 2 Cohort C: CLL/SLL participants with 17p deletion or tumor protein p53
(TP53) mutation who are relapsed or refractory following at least 1 line of
prior therapy
- Part 2 Cohort J: CLL/SLL participants whose disease relapsed or was refractory
to prior therapy with a covalent/irreversible BTKi and BCL2i
- 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 or bone marrow aspirate at Screening
(optional for participants enrolling in Part 1)
Part 2 (Cohorts D to G)
- Has a confirmed diagnosis of and meets the following prior therapy requirements:
- 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(1114), who are relapsed or are refractory to
chemoimmunotherapy and a covalent irreversible 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 or bone marrow aspirate (Cohort D) 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
=450 mg/dL or bone marrow infiltration of 10%
- Has fresh bone marrow aspirate or a lymph node biopsy for biomarker analysis at
Screening or a lymph node biopsy from an archival
Exclusion Criteria:
- Has active HBV/HCV infection (Part 1 and Part 2)
- Has a history of malignancy =3 years before providing documented informed consent.
Participants with basal cell carcinoma of skin, squamous cell carcinoma of skin, or
carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have
undergone potential curative therapy are not excluded. Participants with low-risk,
early-stage prostate cancer (T1-T2a, Gleason score =6, and prostate-specific antigen
<10 ng/mL) either treated with definitive intent or untreated in active surveillance
with SD are not excluded
- Has active central nervous system (CNS) disease
- Has an active infection requiring systemic therapy
- Has received prior systemic anti-cancer therapy within 4 weeks prior to allocation
- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose
of study intervention
- Has any clinically significant gastrointestinal abnormalities that might alter
absorption
- History of severe bleeding disorders (ICTRP)
nicht verfügbar
Primäre und sekundäre Endpunkte
Part 1: Number of participants experiencing dose-limiting toxicities (DLTs);Part 1: Number of participants experiencing adverse events (AEs);Part 1: Number of participants discontinuing study treatment due to AEs;Part 2: Objective Response Rate (ORR) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria 2018 as assessed by independent central review (ICR);Part 2: ORR per Lugano criteria 2014 as assessed by ICR;Part 2: ORR per International Workshop on Waldenstr�m's Macroglobulinemia (IWWM) criteria 2014 as assessed by ICR (ICTRP)
Part 1: Area Under the Curve (AUC) of Nemtabrutinib;Part 1: Minimum Concentration (Cmin) of Nemtabrutinib;Part 1: Maximum Concentration (Cmax) of Nemtabrutinib;Part 1: ORR per iwCLL criteria 2018 as assessed by ICR;Part 1: Duration of Response (DOR) per iwCLL criteria 2018 as assessed by ICR;Part 2: Number of participants experiencing AEs;Part 2: Number of participants discontinuing study treatment due to AEs;Part 2: AUC of Nemtabrutinib;Part 2: Cmin of Nemtabrutinib;Part 2: Cmax of Nemtabrutinib;Part 2: DOR per iwCLL criteria 2018 as assessed by ICR;Part 2: DOR per Lugano criteria 2014 as assessed by ICR;Part 2: DOR per IWWM criteria 2014 as assessed by ICR (ICTRP)
Registrierungsdatum
nicht verfügbar
Einschluss des ersten Teilnehmers
nicht verfügbar
Sekundäre Sponsoren
nicht verfügbar
Weitere Kontakte
Medical Director;Toll Free Number, Trialsites@msd.com, 1-888-577-8839, Merck Sharp & Dohme LLC, (ICTRP)
Sekundäre IDs
MK-1026-003, 2023-504931-42-00, U1111-1290-4004, 2020-002324-36, 1026-003 (ICTRP)
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar
Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT04728893 (ICTRP)
Ergebnisse der Studie
Zusammenfassung der Ergebnisse
nicht verfügbar
Link zu den Ergebnissen im Primärregister
nicht verfügbar