A Phase 3 Study of Nemtabrutinib vs Comparator (Investigator's Choice of Ibrutinib or Acalabrutinib) for 1L CLL/SLL

JRCT ID: jRCT2031230697

Registered date:13/03/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
• Date of first enrollment: 07/05/2024
• Target sample size: 16
• Countries of recruitment: Australia,Japan,Malaysia,Japan,Taiwan,Japan,Thailand,Japan,China,Japan,Belgium,Japan,Czech Republic,Japan,Denmark,Japan,Germany,Japan,Greece,Japan,Israel,Japan,Norway,Japan,Poland,Japan,Portugal,Japan,South Africa,Japan,Spain,Japan,Sweden,Japan,Turkiye,Japan,UK,Japan,Brazil,Japan,Chile,Japan,Colombia,Japan,Mexico,Japan,Peru,Japan,Canada,Japan,USA,Japan
• Study type: Interventional

Intervention(s)

- Nemtabrutinib (MK-1026)
Participants will receive nemtabrutinib at specified dose until disease progression, unacceptable toxicity or until discontinuation criteria are met.
Nemtabrutinib is administered as a daily 65 mg dose, taken orally.

- Ibrutinib/Acalabrutinib
Participants will receive investigator's choice of ibrutinib or acalabrutinib at specified dose until disease progression, unacceptable toxicity or until discontinuation criteria are met.
Ibrutinib is administered as a daily 420 mg dose, taken orally.
Acalabrutinib is administered as 100 mg every 12 hours, taken orally.

Outcome(s)

Primary Outcome

- Objective Response Rate (ORR) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria 2018 as assessed by Blinded Independent Central Review (BICR)
- Progression-Free Survival (PFS) per iwCLL criteria 2018 as assessed by BICR

Secondary Outcome

- Overall Survival (OS)
- Duration of Response (DOR) per iwCLL criteria 2018 as assessed by BICR
- Number of Participants Who Experience One or More Adverse Events (AEs)
- Number of Participants Who Discontinue Study Treatment Due to an AE

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Confirmed diagnosis of CLL/SLL and active disease clearly documented to have a need to initiate therapy.
- Has at least 1 marker of disease burden.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days before randomization.
- 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 deoxyribonucleic acid (DNA) viral load before randomization.
- Participants with history of hepatitis C virus (HCV) infection are eligible if HCV ribonucleic acid (RNA) viral load is undetectable at screening.
- Participants with human immunodeficiency virus (HIV) who meet ALL eligibility criteria.

Exclude criteria

- Has an active HBV/HCV infection.
- Has gastrointestinal (GI) dysfunction that may affect drug absorption.
- Has diagnosis of Richter Transformation or active central nervous system (CNS) involvement by CLL/SLL.
- Has had acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in the past 12 months before screening.
- Has QT interval corrected (QTc) prolongation or other significant electrocardiogram (ECG) abnormalities.
- Has hypersensitivity to nemtabrutinib or contraindication to ibrutinib or acalabrutinib, or any of the excipients.
- Has history of severe bleeding disorder.
- Has history of second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
- Has received any systemic anticancer therapy for CLL/SLL.
- Is currently being treated with p-glycoprotein (P-gp) substrates with a narrow therapeutic index, cytochrome P450 3A (CYP3A) strong inducers or CYP3A strong inhibitors.
- Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids.
- Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
- Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration.
- Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication.
- Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed.
- Has active infection requiring systemic therapy.
- Participants who have not adequately recovered from major surgery or have ongoing surgical complications.

Related Information

• Primary Sponsor: Koh Yasuhiro
• Secondary ID(s): NCT06136559