Back to resultsA Study of Nemtabrutinib (MK-1026) in China Participants With Relapsed or Refractory Hematologic Malignancies (MK-1026-005)
Primary Purpose
Hematological Malignancies
Status
Active
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Nemtabrutinib
Sponsored by
About this trial
This is an interventional treatment trial for Hematological Malignancies
Eligibility Criteria
Inclusion Criteria:
- Relapsed or refractory participants with a diagnosis of B-cell Non-Hodgkin's Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) or Waldenström's Macroglobulinemia (WM) who have received no more than 4 prior standard systemic therapies. Participants must have failed or are intolerant to standard therapies and cannot be a candidate for standard salvage regimens and those with low grade lymphoma must be progressing and requiring treatment
- Must have received prior systemic treatment before joining this study
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- HBV/HCV viral load undetectable or no history of HBV/HCV
- Has adequate organ function
- Male participants agree to be abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 30 days after the last dose of the study intervention
- Female participant is not a Women of Child Bearing Potential (WOCBP) or is a WOCBP using contraception during the intervention period and for at least 30 days after the last dose of the study intervention
Exclusion Criteria:
- Has a history of prior cancer within <3 years, except for adequately treated basal cell or squamous cell carcinoma of the skin, cervical cancer in situ, or other in situ carcinomas
- Has active primary tumor involvement of central nervous system (CNS) disease
- Has an active infection requiring systemic therapy
- Has a known history of Human Immunodeficiency Virus (HIV) infection
- Has an uncontrolled illness including but not limited to ongoing symptomatic congestive heart failure (New York Heart Association Class III or IV heart failure), unstable angina pectoris, cardiac arrhythmia, and psychiatric illness
- Had immunotherapy, radioimmunotherapy, biological therapy, chemotherapy, or treatment with an investigational product ≤4 weeks prior to treatment initiation
- Has any clinically significant gastrointestinal abnormalities that might alter absorption
Sites / Locations
- Guangdong Provincial People's Hospital-hematology department ( Site 1002)
- SUN YAT-SEN UNIVERSITY CANCER CENTRE-Internal medicine ( Site 1007)
- Henan Cancer Hospital-hematology department ( Site 1003)
- Hunan Cancer Hospital ( Site 1004)
- Institute of hematology&blood disease hospital-Hematology ( Site 1001)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Nemtabrutinib
Arm Description
Participants receive nemtabrutinib at specified dose orally once daily (QD) until progressive disease (PD) or discontinuation.
Outcomes
Primary Outcome Measures
Number of Participants who Experience Adverse Events (AEs)
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
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.
Maximum Concentration (Cmax) of Nemtabrutinib
Cmax is the maximum concentration of nemtabrutinib observed in plasma. Blood samples collected at designated timepoints will be used to determine Cmax.
Minimum Concentration (Cmin) of Nemtabrutinib
Cmin is the minimum concentration of nemtabrutinib observed in plasma. Blood samples collected at designated timepoints will be used to determine Cmin.
Area Under the Plasma Concentration-Time Curve from 0 to 24 Hours (AUC0-24) of Nemtabrutinib
AUC0-24 is the area under the curve of plasma concentration of nemtabrutinib from time 0 to 24 hours. Blood samples collected at designated timepoints will be used to determine AUC0-24.
Time to Maximum Concentration (Tmax) of Nemtabrutinib
Tmax is the time to reach maximum concentration of nemtabrutinib. Blood samples collected at designated timepoints will be used to determine Tmax.
Secondary Outcome Measures
Objective Response Rate (ORR) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 as Assessed by the Investigator
ORR per iwCLL criteria 2018 is defined as the percentage of participants achieving a complete response (CR), complete response with incomplete bone marrow (BM) recovery (CRi), nodular partial response (nPR) or partial response (PR). CR is defined as meeting the following criteria: no lymph nodes ≥1.5 cm, spleen size <13 cm, liver normal; no constitutional symptoms, normal lymphocyte count, platelets ≥100 x 10^9/L; hemoglobin ≥11 g/dL; and normocellular marrow (no CLL cells or B lymphoid nodules). CRi is defined as meeting CR criteria but with incomplete bone marrow recovery. nPR is defined as having features of CR but with lymphoid nodules in the marrow. PR is defined as ≥50% decrease in ≥2 of the following: lymph nodes, liver and/or spleen size, lymphocytes PLUS ≥1 of the following met: platelets ≥100 x 10^9/L or >50% increase from screening, hemoglobin ≥11 g/dL or >50% increase from screening, CLL cells or B lymphoid nodules in marrow.
ORR per International Workshop on Waldenström's Macroglobulinemia (IWWM) Criteria 2014 as Assessed by the Investigator
ORR per IWWM criteria 2014 is defined as the percentage of participants achieving a CR, very good partial response (VGPR), or PR. CR is defined as all lymph nodes are normal in size (none ≥15 mm), liver and spleen normal in size, serum immunoglobulin M (IgM) values in the normal range, disappearance of monoclonal protein by immunofixation (confirmation needed with a second immunofixation at any subsequent timepoint), and no histological evidence of BM involvement. VGPR is defined as ≥50% decrease from baseline in sum of product of diameter (SPD) of lymph nodes (if abnormal at baseline) ≥50% decrease from baseline in the abnormal portion of the spleen (if previously abnormal) and ≥90% decrease from baseline in serum IgM or serum IgM values in normal range. PR is defined as ≥50% decrease from baseline in SPD of lymph nodes (if abnormal at baseline) ≥50% decrease from baseline in serum IgM and ≥50% decrease from baseline in the abnormal portion of the spleen (if previously abnormal).
ORR per Lugano Criteria 2014 as Assessed by the Investigator
ORR per Lugano criteria 2014 is defined as the percentage of participants achieving a CR or PR. CR defined as EITHER CR by imaging (computed tomography [CT]): all lymph nodes normal (none ≥15 mm) and normal liver and spleen OR complete metabolic response (CMR): assessing fluorodeoxyglucose (FDG) metabolic activity in lymphomatous lesions AND bone marrow normal by morphology. PR defined as EITHER PR by imaging (CT) with ≥50% decrease in the SPD of target lesions, no worsening of nontarget lesions, no new lesions and ≥50% spleen abnormal portion OR Partial Metabolic Response (PMR) with no new lesions and decreased overall uptake AND residual BM abnormalities; OR CR by imaging with residual BM abnormalities; OR PR by imaging without residual BM abnormalities.
Duration of Response (DOR) per iwCLL Criteria 2018 as Assessed by the Investigator
For participants with CR, CRi, nPR, or PR per iwCLL 2018 criteria, DOR is defined as the time from the first documented evidence of objective response until disease progression or death due to any cause, whichever occurs first. CR is defined as meeting the following criteria: no lymph nodes ≥1.5 cm, spleen size <13 cm, liver normal; no constitutional symptoms, normal lymphocyte count, platelets ≥100 x 10^9/L; hemoglobin ≥11 g/dL; and normocellular marrow (no CLL cells or B lymphoid nodules). CRi is defined as meeting CR criteria but with hypocellular bone marrow. nPR is defined as having features of CR but with lymphoid nodules in the marrow. PR is defined as ≥50% decrease in ≥2 of the following: lymph nodes, liver and/or spleen size, lymphocytes PLUS ≥1 of the following met: platelets ≥100 x 10^9/L or >50% increase from screening, hemoglobin ≥11 g/dL or >50% increase from screening, CLL cells or B lymphoid nodules in marrow.
DOR per IWWM Criteria 2014 as Assessed by the Investigator
For participants with CR, VGPR, or PR per IWWM criteria 2014, DOR defined as the time from first documented evidence of objective response until PD or death due to any cause, whichever occurs first. CR defined as all lymph nodes normal in size (none ≥15 mm), liver and spleen normal in size, serum IgM values in normal range, disappearance of monoclonal protein by immunofixation (confirmation needed with second immunofixation at any subsequent timepoint), and no histological evidence of BM involvement. VGPR defined as ≥50% decrease from baseline in SPD of lymph nodes (if abnormal at baseline), ≥50% decrease from baseline in abnormal portion of the spleen (if previously abnormal), and ≥90% decrease from baseline in serum IgM, or serum IgM values in normal range. PR is defined as ≥50% decrease from baseline in SPD of lymph nodes (if abnormal at baseline), ≥50% decrease from baseline in serum IgM, and ≥50% decrease from baseline in abnormal portion of the spleen (if previously abnormal).
DOR per Lugano Criteria 2014 as Assessed by the Investigator
For participants with CR or PR per Lugano criteria 2014, DOR is defined as the time from the first documented evidence of objective response until PD or death due to any cause, whichever occurs first. CR defined as EITHER CR by imaging (CT): all lymph nodes normal (none ≥15 mm) and normal liver and spleen OR CMR: assessing FDG metabolic activity in lymphomatous lesions AND BM normal by morphology. PR defined as EITHER PR by imaging (CT) with ≥50% decrease in the SPD of target lesions, no worsening of nontarget lesions, no new lesions and ≥50% spleen abnormal portion OR PMR with no new lesions and decreased overall uptake AND residual BM abnormalities; OR CR by imaging with residual BM abnormalities; OR PR by imaging without residual BM abnormalities.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05347225
Brief Title
A Study of Nemtabrutinib (MK-1026) in China Participants With Relapsed or Refractory Hematologic Malignancies (MK-1026-005)
Official Title
A Phase 1 Clinical Study to Investigate the Safety, Pharmacokinetics and Efficacy of MK-1026 in China Participants With Relapsed or Refractory Hematologic Malignancies
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 9, 2022 (Actual)
Primary Completion Date
April 28, 2025 (Anticipated)
Study Completion Date
April 28, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety, pharmacokinetics (PK) and preliminary efficacy of oral nemtabrutinib in Chinese participants at least 18 years of age who have Relapsed/Refractory hematologic malignancies.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematological Malignancies
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Nemtabrutinib
Arm Type
Experimental
Arm Description
Participants receive nemtabrutinib at specified dose orally once daily (QD) until progressive disease (PD) or discontinuation.
Intervention Type
Drug
Intervention Name(s)
Nemtabrutinib
Other Intervention Name(s)
MK-1026, ARQ 531
Intervention Description
Nemtabrutinib tablets will be administered orally QD.
Primary Outcome Measure Information:
Title
Number of Participants who Experience Adverse Events (AEs)
Description
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.
Time Frame
Up to ~ 35 months
Title
Number of Participants Discontinuing Study Treatment due to AEs
Description
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.
Time Frame
Up to ~ 35 months
Title
Maximum Concentration (Cmax) of Nemtabrutinib
Description
Cmax is the maximum concentration of nemtabrutinib observed in plasma. Blood samples collected at designated timepoints will be used to determine Cmax.
Time Frame
Day 1 of Cycles 1 and 2: Pre-dose,1, 2, 4, 6, 8, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2 hours post-dose (up to ~57 days). Each cycle is 28 days
Title
Minimum Concentration (Cmin) of Nemtabrutinib
Description
Cmin is the minimum concentration of nemtabrutinib observed in plasma. Blood samples collected at designated timepoints will be used to determine Cmin.
Time Frame
Day 1 of Cycles 1 and 2: Pre-dose,1, 2, 4, 6, 8, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2 hours post-dose (up to ~57 days). Each cycle is 28 days
Title
Area Under the Plasma Concentration-Time Curve from 0 to 24 Hours (AUC0-24) of Nemtabrutinib
Description
AUC0-24 is the area under the curve of plasma concentration of nemtabrutinib from time 0 to 24 hours. Blood samples collected at designated timepoints will be used to determine AUC0-24.
Time Frame
Day 1 of Cycles 1 and 2: Pre-dose,1, 2, 4, 6, 8, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2 hours post-dose (up to ~57 days). Each cycle is 28 days
Title
Time to Maximum Concentration (Tmax) of Nemtabrutinib
Description
Tmax is the time to reach maximum concentration of nemtabrutinib. Blood samples collected at designated timepoints will be used to determine Tmax.
Time Frame
Day 1 of Cycles 1 and 2: Pre-dose,1, 2, 4, 6, 8, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2 hours post-dose (up to ~57 days). Each cycle is 28 days
Secondary Outcome Measure Information:
Title
Objective Response Rate (ORR) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 as Assessed by the Investigator
Description
ORR per iwCLL criteria 2018 is defined as the percentage of participants achieving a complete response (CR), complete response with incomplete bone marrow (BM) recovery (CRi), nodular partial response (nPR) or partial response (PR). CR is defined as meeting the following criteria: no lymph nodes ≥1.5 cm, spleen size <13 cm, liver normal; no constitutional symptoms, normal lymphocyte count, platelets ≥100 x 10^9/L; hemoglobin ≥11 g/dL; and normocellular marrow (no CLL cells or B lymphoid nodules). CRi is defined as meeting CR criteria but with incomplete bone marrow recovery. nPR is defined as having features of CR but with lymphoid nodules in the marrow. PR is defined as ≥50% decrease in ≥2 of the following: lymph nodes, liver and/or spleen size, lymphocytes PLUS ≥1 of the following met: platelets ≥100 x 10^9/L or >50% increase from screening, hemoglobin ≥11 g/dL or >50% increase from screening, CLL cells or B lymphoid nodules in marrow.
Time Frame
Up to ~ 35 months
Title
ORR per International Workshop on Waldenström's Macroglobulinemia (IWWM) Criteria 2014 as Assessed by the Investigator
Description
ORR per IWWM criteria 2014 is defined as the percentage of participants achieving a CR, very good partial response (VGPR), or PR. CR is defined as all lymph nodes are normal in size (none ≥15 mm), liver and spleen normal in size, serum immunoglobulin M (IgM) values in the normal range, disappearance of monoclonal protein by immunofixation (confirmation needed with a second immunofixation at any subsequent timepoint), and no histological evidence of BM involvement. VGPR is defined as ≥50% decrease from baseline in sum of product of diameter (SPD) of lymph nodes (if abnormal at baseline) ≥50% decrease from baseline in the abnormal portion of the spleen (if previously abnormal) and ≥90% decrease from baseline in serum IgM or serum IgM values in normal range. PR is defined as ≥50% decrease from baseline in SPD of lymph nodes (if abnormal at baseline) ≥50% decrease from baseline in serum IgM and ≥50% decrease from baseline in the abnormal portion of the spleen (if previously abnormal).
Time Frame
Up to ~ 35 months
Title
ORR per Lugano Criteria 2014 as Assessed by the Investigator
Description
ORR per Lugano criteria 2014 is defined as the percentage of participants achieving a CR or PR. CR defined as EITHER CR by imaging (computed tomography [CT]): all lymph nodes normal (none ≥15 mm) and normal liver and spleen OR complete metabolic response (CMR): assessing fluorodeoxyglucose (FDG) metabolic activity in lymphomatous lesions AND bone marrow normal by morphology. PR defined as EITHER PR by imaging (CT) with ≥50% decrease in the SPD of target lesions, no worsening of nontarget lesions, no new lesions and ≥50% spleen abnormal portion OR Partial Metabolic Response (PMR) with no new lesions and decreased overall uptake AND residual BM abnormalities; OR CR by imaging with residual BM abnormalities; OR PR by imaging without residual BM abnormalities.
Time Frame
Up to ~ 35 months
Title
Duration of Response (DOR) per iwCLL Criteria 2018 as Assessed by the Investigator
Description
For participants with CR, CRi, nPR, or PR per iwCLL 2018 criteria, DOR is defined as the time from the first documented evidence of objective response until disease progression or death due to any cause, whichever occurs first. CR is defined as meeting the following criteria: no lymph nodes ≥1.5 cm, spleen size <13 cm, liver normal; no constitutional symptoms, normal lymphocyte count, platelets ≥100 x 10^9/L; hemoglobin ≥11 g/dL; and normocellular marrow (no CLL cells or B lymphoid nodules). CRi is defined as meeting CR criteria but with hypocellular bone marrow. nPR is defined as having features of CR but with lymphoid nodules in the marrow. PR is defined as ≥50% decrease in ≥2 of the following: lymph nodes, liver and/or spleen size, lymphocytes PLUS ≥1 of the following met: platelets ≥100 x 10^9/L or >50% increase from screening, hemoglobin ≥11 g/dL or >50% increase from screening, CLL cells or B lymphoid nodules in marrow.
Time Frame
Up to ~ 35 months
Title
DOR per IWWM Criteria 2014 as Assessed by the Investigator
Description
For participants with CR, VGPR, or PR per IWWM criteria 2014, DOR defined as the time from first documented evidence of objective response until PD or death due to any cause, whichever occurs first. CR defined as all lymph nodes normal in size (none ≥15 mm), liver and spleen normal in size, serum IgM values in normal range, disappearance of monoclonal protein by immunofixation (confirmation needed with second immunofixation at any subsequent timepoint), and no histological evidence of BM involvement. VGPR defined as ≥50% decrease from baseline in SPD of lymph nodes (if abnormal at baseline), ≥50% decrease from baseline in abnormal portion of the spleen (if previously abnormal), and ≥90% decrease from baseline in serum IgM, or serum IgM values in normal range. PR is defined as ≥50% decrease from baseline in SPD of lymph nodes (if abnormal at baseline), ≥50% decrease from baseline in serum IgM, and ≥50% decrease from baseline in abnormal portion of the spleen (if previously abnormal).
Time Frame
Up to ~ 35 months
Title
DOR per Lugano Criteria 2014 as Assessed by the Investigator
Description
For participants with CR or PR per Lugano criteria 2014, DOR is defined as the time from the first documented evidence of objective response until PD or death due to any cause, whichever occurs first. CR defined as EITHER CR by imaging (CT): all lymph nodes normal (none ≥15 mm) and normal liver and spleen OR CMR: assessing FDG metabolic activity in lymphomatous lesions AND BM normal by morphology. PR defined as EITHER PR by imaging (CT) with ≥50% decrease in the SPD of target lesions, no worsening of nontarget lesions, no new lesions and ≥50% spleen abnormal portion OR PMR with no new lesions and decreased overall uptake AND residual BM abnormalities; OR CR by imaging with residual BM abnormalities; OR PR by imaging without residual BM abnormalities.
Time Frame
Up to ~ 35 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Relapsed or refractory participants with a diagnosis of B-cell Non-Hodgkin's Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL) or Waldenström's Macroglobulinemia (WM) who have received no more than 4 prior standard systemic therapies. Participants must have failed or are intolerant to standard therapies and cannot be a candidate for standard salvage regimens and those with low grade lymphoma must be progressing and requiring treatment
Must have received prior systemic treatment before joining this study
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
HBV/HCV viral load undetectable or no history of HBV/HCV
Has adequate organ function
Male participants agree to be abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 30 days after the last dose of the study intervention
Female participant is not a Women of Child Bearing Potential (WOCBP) or is a WOCBP using contraception during the intervention period and for at least 30 days after the last dose of the study intervention
Exclusion Criteria:
Has a history of prior cancer within <3 years, except for adequately treated basal cell or squamous cell carcinoma of the skin, cervical cancer in situ, or other in situ carcinomas
Has active primary tumor involvement of central nervous system (CNS) disease
Has an active infection requiring systemic therapy
Has a known history of Human Immunodeficiency Virus (HIV) infection
Has an uncontrolled illness including but not limited to ongoing symptomatic congestive heart failure (New York Heart Association Class III or IV heart failure), unstable angina pectoris, cardiac arrhythmia, and psychiatric illness
Had immunotherapy, radioimmunotherapy, biological therapy, chemotherapy, or treatment with an investigational product ≤4 weeks prior to treatment initiation
Has any clinically significant gastrointestinal abnormalities that might alter absorption
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Guangdong Provincial People's Hospital-hematology department ( Site 1002)
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510000
Country
China
Facility Name
SUN YAT-SEN UNIVERSITY CANCER CENTRE-Internal medicine ( Site 1007)
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
511400
Country
China
Facility Name
Henan Cancer Hospital-hematology department ( Site 1003)
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450008
Country
China
Facility Name
Hunan Cancer Hospital ( Site 1004)
City
Changsha
State/Province
Hunan
ZIP/Postal Code
410013
Country
China
Facility Name
Institute of hematology&blood disease hospital-Hematology ( Site 1001)
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Links:
URL
http://merckoncologyclinicaltrials.com
Description
Merck Oncology Clinical Trials Information
Learn more about this trial
A Study of Nemtabrutinib (MK-1026) in China Participants With Relapsed or Refractory Hematologic Malignancies (MK-1026-005)
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