Phase-2-Studie zur Beurteilung der Wirksamkeit und Sicherheit von MK-1026 in Teilnehmenden mit bösartigen hämatologische Erkrankungen.

Drug: Nemtabrutinib

Gender: All
Maximum age: N/A
Minimum age: 18 Years
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(11;14), 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