Mature B-cell Neoplasms
Conditions
Brief summary
The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of nemtabrutinib in Japanese participants with mature B-cell neoplasms.
Interventions
DRUGNemtabrutinib
Nemtabrutinib tablets will be administered orally QD at dosage of 45 mg or 65 mg
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The main inclusion and
Exclusion criteria
include but are not limited to the following: Inclusion Criteria: * Histologically confirmed B-cell malignancy: * Chronic lymphocytic leukemia (CLL) * Small lymphocytic lymphoma (SLL) * Waldenström's macroglobulinemia (WM) * Lymphoplasmacytic lymphoma (LPL) * Other B-cell neoplasm * Failed or intolerant to either at least 2 prior regimens given in combination or sequentially OR have received 1 prior Bruton's tyrosine kinase (BTK)-containing regimen when a BTK inhibitor is approved as first line therapy * Have the ability to swallow and retain oral medication * Is Japanese
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience Dose Limiting Toxicities (DLTs) Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0 | Up to approximately 4 weeks | A DLT is ≥1 of: Grade ≥3 nonhematologic toxicity with exception of Grade 3 nausea, vomiting, diarrhea, rash, fatigue, and uncontrolled hypertension lasting \>72 hours despite optimal supportive case; Grade 4 hematologic toxicity lasting \>7 days, Grade 4 platelet count decreased of any duration (with exceptions), or Grade 3 platelet count decreased with bleeding (with exceptions), or Grade 3 or higher febrile neutropenia of any duration; Grade 3 or Grade 4 nonhematologic laboratory abnormality, if results in drug induced liver injury (DILI), or medical intervention is required, or the abnormality leads to hospitalization, or the abnormality persists for \>1 week (with exceptions); missing \>25% of nemtabrutinib doses as a result of drug-related AE(s); Grade 5 toxicity. Toxicities will be graded using NCI-CTCAE version 5.0 except hematologic toxicities in participants with chronic lymphocytic leukemia (CLL) assessed according to the International Workshop on CLL (iwCLL) criteria. |
| Number of Participants Who Experience Adverse Events (AEs) | Up to approximately 26 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
| Number of Participants Discontinuing Study Treatment Due to AEs | Up to approximately 26 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Dosing to 24 Hours Postdose (AUC0-24) of Nemtabrutinib | Day 1: Pre-dose and 1, 2, 4, 6, 8, 10, and 24 hours post-dose | AUC0-24 is the area under the curve of plasma concentration of nemtabrutinib from dosing to 24 hours postdose. |
| Minimum Concentration (Cmin) of Nemtabrutinib | Day 1: Pre-dose and 1, 2, 4, 6, 8, 10, and 24 hours post-dose | Cmin is the lowest observed plasma concentration. |
| Maximum Concentration (Cmax) of Nemtabrutinib | Day 1: Pre-dose and 1, 2, 4, 6, 8, 10, and 24 hours post-dose | Cmax is the lowest observed plasma concentration. |
| Time to Maximum Concentration (Tmax) of Nemtabrutinib | Day 1: Pre-dose and 1, 2, 4, 6, 8, 10, and 24 hours post-dose | Tmax is the time to reach Cmax. |
| Objective Response Rate (ORR) as Assessed by Investigator | Up to approximately 26 months | ORR is the proportion of participants in the analysis population with objective response. Objective response is defined as participants who achieve at least a partial response (PR) per disease-specific criteria as assessed by investigator. Data are presented separately for participants with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and non-CLL/SLL participants. |
| Duration of Response (DOR) as Assessed by Investigator | Up to approximately 26 months | For participants who demonstrate an objective response as assessed by investigator, per disease-specific criteria, duration of response is defined as the time from the first documented evidence of an objective response until disease progression or death due to any cause, whichever occurs first. |
Countries
Japan
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 71.3 Years STANDARD_DEVIATION 14.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 3 / 4 |
| other Total, other adverse events | 3 / 3 | 4 / 4 |
| serious Total, serious adverse events | 1 / 3 | 1 / 4 |
Outcome results
None listed