MedDRA version: 20.0 Level: PT Classification code 10003899 Term: B-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: HLT Classification code 10026798 Term: Mantle cell lymphomas System Organ Class: 100000004851
Conditions
Interventions
Product Name: MK-1026
Pharmaceutical Form: Tablet
CAS Number: 2095393-15-8
Current Sponsor code: MK-1026
Other descriptive name: ARQ 531
Concentration unit: mg milligram(s)
Concentration type: equal
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. In Part 1 and Part 2 (Cohorts A to C) has a confirmed diagnosis of CLL/SLL with; • A response to previous treatment of o At least 2 lines of prior therapy (Part 1 only) o Part 2 Cohort A: CLL/SLL participants who are relapsed or refractory to prior therapy with a covalent, irreversible BTKi, BCL2i and PI3Ki. o Part 2 Cohort B: CLL/SLL participants who are relapsed or refractory following at least 1 line of prior therapy and are BTKi treatment naïve. o Part 2 Cohort C: CLL/SLL participants with 17p deletion who are relapsed or refractory following at least 1 line of prior therapy. • Active disease for CLL/SLL clearly documented to initiate therapy. • Provision of an evaluable core or excisional lymph node biopsy for biomarker analysis from an archival (=60 days relative to the date of sample submission to the central laboratory) or newly obtained biopsy at Screening. 2. Part 2 (Cohorts D to G): • Has a confirmed diagnosis of and response to previous treatment of one of the following: o Cohort D: participants with Richter’s transformation who are relapsed or refractory following at least 1 line of prior therapy. o Cohort E: 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. o Cohort F: participants with MZL (including splenic, nodal, and extra nodal MZL) who are relapsed or refractory to chemoimmunotherapy and a covalent irreversible BTKi. o Cohort G: participants with FL who are relapsed or refractory to chemoimmunotherapy, immunomodulatory agents (i.e. lenalidomide + rituximab), and a PI3Ki. • Have measurable disease defined as at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan. A minimum measurement must be >15 mm in the longest diameter or >10 mm in the short axis. • Provide an evaluable core or excisional lymph node biopsy for biomarker analysis from an archival (=60 days relative to the date of sample submission to the central laboratory) or newly obtained biopsy at Screening. 3. Part 2 (Cohort H): confirmed diagnosis of WM; participants who are relapsed or refractory to chemoimmunotherapy and a covalent irreversible BTKi. • Active disease is defined as 1 of the following: o Systemic symptoms – Fever, drenching night sweats, fatigue, weight loss, and/or severe neuropathy. o Physical findings – Symptomatic or bulky (=5 cm) lymphadenopathy, symptomatic hepatomegaly, and/or symptomatic splenomegaly. o Laboratory abnormalities – Hemoglobin =10 g/dL or platelet count 15 mm in the longest diameter or >10 mm in the short axis); IgM =4500 g/dL; or bone marrow infiltration of 70%. • Provide an evaluable core or excisional lymph node biopsy for biomarker analysis from an archival (=60 days relative to the date of sample submission to the central laboratory) or newly obtained biopsy at Screening. 4. Have an ECOG performance status of 0 to 2 within 7 days prior to allocation. 5. Have a life expectancy of at least 3 months, based on t
Exclusion criteria
Exclusion criteria: 1. Part 1 and Part 2 participants: active HBV/HCV infection. See Inclusion Criteria 7 (HBV) and 8 (HCV) for requirements. 2. Has a history of malignancy =3 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer. 3. Has active CNS disease. 4. Has an active infection requiring systemic therapy. 5. Has a known history of HIV infection. No HIV testing is required unless mandated by local health authority. 6. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. 7. Has QTc prolongation (defined as a QTcF >450 msecs) or other significant ECG abnormalities including 2nd degree AV block type II, 3rd degree AV block, or bradycardia (ventricular rate less than 50 beats/min). 8. Has received prior systemic anti-cancer therapy within 4 weeks prior to allocation. 9. Is currently being treated with the following drugs: •CYP 2C9 substrates with a narrow therapeutic index (such as warfarin, phenytoin) •CYP 2C8 substrates with a narrow therapeutic index (such as paclitaxel) •CYP 2C19 substrates with a narrow therapeutic index (such as S-mephenytoin) •CYP 2D6 substrates with a narrow therapeutic index (such as thioridazine, pimozide) •P-gp substrates with a narrow therapeutic index (such as digoxin) 10. 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. 11. Prior exposure to non-covalent, reversible BTK inhibitors. 12. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study. 13. Has any clinically significant gastrointestinal abnormalities that might alter absorption.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. Part 1: To determine the safety and tolerability and to establish a recommended Phase 2 dose (RP2D) of MK-1026. 2. Part 2: Cohorts A to C (chronic Lymphocytic Leukemia [CLL]/Small Lymphocytic Lymphoma [SLL]): To evaluate the objective response rate (ORR) following administration with MK-1026 per International Workshop on CLL (iwCLL) criteria 2018 as assessed by independent central review (ICR). 3. Part 2: Cohorts D to G (Richter’s Transformation [RT], Mantle cell Lymphoma [MCL], Marginal zone Lymphoma [MZL], Follicular Lymphoma [FL]): To evaluate the ORR following administration with MK-1026 per the Lugano criteria 2014 as assessed by ICR. 4. Part 2: Cohort H (Waldenström’s Macroglobulinemia [WM]): To evaluate the ORR following administration with MK-1026 per International Workshop on WM (IWWM) 2014 as assessed by ICR. ;Secondary Objective: 1. Part 1: To characterize the pharmacokinetic (PK) profile of MK-1026. 2. Part 1: To evaluate the ORR and duration of response (DOR) following administration with MK-1026 for CLL/SLL participants per iwCLL criteria 2018 as assessed by ICR. 3. Part 2: All Cohorts: To determine the safety and tolerability of MK-1026. 4. Part 2: All Cohorts: To characterize the PK profile of MK-1026. 5. Part 2: Cohorts A to C (CLL/SLL): To evaluate DOR following administration with MK-1026 per iwCLL criteria 2018 as assessed by ICR. 6. Pt 2: Cohorts D to G (RT, MCL, MZL, FL): To evaluate the DOR following administration with MK-1026 per the Lugano criteria 2014 as assessed by ICR. 7. Part 2: Cohort H (WM): To evaluate the DOR of MK-1026 per IWWM 2014 as assessed by ICR ;Primary end point(s): 1. Part 1: Number of participants experiencing dose-limiting toxicities (DLTs) 2. Part 1: Number of participants experiencing adverse events (AEs) 3. Part 1: Number of participants discontinuing study treatment due to AEs 4. Part 2 (Cohorts A to C): Objective Response Rate (ORR) per International Workshop on Chronic Lymphocytic Leukemia ( | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Part. 1: Area Under the Curve (AUC) of MK-1026 2. Part. 1: Minimum Concentration (Cmin) of MK-1026 3. Part 1: Maximum Concentration (Cmax) of MK-1026 4. Part 1: ORR per iwCLL criteria 2018 as assessed by ICR 5. Part 1: Duration of Response (DOR) per iwCLL criteria 2018 as assessed by ICR 6. Part 2 (All Cohorts): Number of participants experiencing AEs 7. Part 2 (All Cohorts): Number of participants discontinuing study treatment due to AEs 8. Part. 2 (All Cohorts): AUC of MK-1026 9. Part. 2 (All Cohorts): Cmin of MK-1026 10. Part 2 (All Cohorts): Cmax of MK-1026 11. Part 2 (Cohorts A to C): DOR per iwCLL criteria 2018 as assessed by ICR 12. Part 2 (Cohorts D to G): DOR per Lugano criteria 2014 as assessed by ICR 13. Part 2 (Cohort H): DOR per IWWM 2014 as assessed by ICR ;Timepoint(s) of evaluation of this end point: 1. At designated time points (up to ~57 days) 2. At designated time points (up to ~57 days) 3. At designated time points (up to ~57 days) 4. Up to ~78 months 5. Up to ~78 months 6. Up to ~78 months 7. Up to ~78 months 8. At designated time points (up to ~57 days) 9. At designated time points (up to ~57 days) 10. At designated time points (up to ~57 days) 11. Up to ~78 months 12. Up to ~78 months 13. Up to ~78 months | — |
Countries
Argentina, Australia, Brazil, Canada, Colombia, Czechia, Czech Republic, Denmark, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Korea, Republic of, Netherlands, Poland, Portugal, Romania, Russian Federation, Spain, Sweden, Switzerland, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Trial Operations
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
Outcome results
None listed