A Phase 2 Study to Evaluate the Efficacy and Safety of MK-1026 in Participants with Hematologic Malignancies

Phase 1

• Conditions: MedDRA version: 20.0Level: PTClassification code 10003899Term: B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.0Level: LLTClassification code 10008976Term: Chronic lymphocytic leukemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: HLTClassification code 10026798Term: Mantle cell lymphomasSystem Organ Class: 100000004851; MedDRA version: 21.1Level: LLTClassification code 10054693Term: Von Waldenstrom macroglobulinemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10076596Term: Marginal zone lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-002324-36-CZ
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-09-01
• Last Update Posted: 26 February 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

1. In Part 1 and Part 2 (Cohorts A to C) 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 BTKi and a BCL2i. CLL participants must have received and failed, been intolerant to, or determined by their treating physician to be a poor PI3Ki candidate or ineligible for a PI3Ki per local (institution) 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 naïve
-Part 2 Cohort C: CLL/SLL participants with 17p deletion or TP53 mutation (as determined locally) who are relapsed or refractory following at least 1 line of prior therapy
-Active disease for CLL/SLL clearly documented to initiate therapy
-For SLL participants in Part 2: Participants with lymphoma must provide a lymph node biopsy for biomarker analysis from an archival 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:
*Cohort D:participants with RT who are relapsed or refractory following at least 1 line of prior therapy
*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
*Cohort F: participants with MZL (including splenic, nodal, and extranodal MZL) who are relapsed or refractory to chemoimmunotherapy and a covalent irreversible BTKi
*Cohort G: participants with FL who are relapsed or refractory to chemoimmunotherapy, and immunomodulatory agents (i.e. lenalidomide + rituximab)
-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 lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy at Screening
3.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
-Active disease is defined as 1 of the following:
*Systemic symptoms – Fever, drenching night sweats, fatigue, weight loss, and/or severe neuropathy
*Physical findings – Symptomatic or bulky (=5 cm) lymphadenopathy, symptomatic hepatomegaly, and/or symptomatic splenomegaly
*Laboratory abnormalities – Hemoglobin =10 g/dL or platelet count <100,000/µL
*Coexisting disease – Immunoglobulin light chain amyloidosis with organ dysfunction, symptomatic cryoglobulinemia, cold agglutinin anemia, immune hemolytic anemia and/or thrombocytopenia, or nephropathy due to WM
-Have 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%
-Provide a fresh bone marrow aspirate for biomarker analysis at Screening. A lymph node biopsy from an archival or newly obtained biopsy at screening is also acceptable
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 the investigator assessment(all cohorts except D [RT])
6.Have

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 providing documented 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. Exclusion criterion removed.
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 second degree AV block type II, third degree AV block, or bradycardia (ventricular rate less than 50 beats/min).
8. Has received prior systemic anticancer therapy within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibody) prior to allocation.
9. Is currently being treated with the following drugs:
-CYP2C8 substrates with a narrow therapeutic index (such as paclitaxel)
-P-gp substrates with a narrow therapeutic index (such as digoxin)
-CYP3A strong inducers (such as rifampin)
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 noncovalent, 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.
14. Has a known severe hypersensitivity (=Grade 3) to nemtabrutinib, its active substance and/or any of its excipients. Refer to the IB for a list of excipients.
15. History of bleeding disorders

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified