A Phase 3, Randomized Study to Compare Nemtabrutinib Versus Comparator (Investigator’s Choice of Ibrutinib or Acalabrutinib) in Participants With Untreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BELLWAVE 011)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2024-01-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2022-501697-19-00

WHO UTN

U1111-1281-7895

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Pharmacogenomic, Efficacy, Safety

1. To compare nemtabrutinib to ibrutinib or acalabrutinib with respect to ORR per iwCLL criteria 2018 as assessed by BICR.
2. To compare nemtabrutinib to ibrutinib or acalabrutinib with respect to PFS per iwCLL criteria 2018 as assessed by BICR.

Secondary objectives 3

1. To compare nemtabrutinib to ibrutinib or acalabrutinib with respect to OS.
2. To evaluate DOR per iwCLL criteria 2018 as assessed by BICR.
3. To evaluate the safety and tolerability of nemtabrutinib.

Conditions and MedDRA coding

Small Lymphocytic Lymphoma (SLL) / Untreated Chronic Lymphocytic Leukemia (CLL)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Confirmed diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and active disease clearly documented to have a need to initiate therapy.
2. Has at least 1 marker of disease burden.
3. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days before randomization.
4. Has the ability to swallow and retain oral medication.
5. 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.
6. Participants with history of hepatitis C virus (HCV) infection are eligible if HCV ribonucleic acid (RNA) viral load is undetectable at screening.
7. Participants with human immunodeficiency virus (HIV) who meet ALL eligibility criteria.

Exclusion criteria 17

1. Has an active hepatitis B virus/ hepatitis C virus (HBV/HCV) infection.
2. Has gastrointestinal (GI) dysfunction that may affect drug absorption.
3. Has diagnosis of Richter Transformation or active central nervous system (CNS) involvement by CLL/SLL.
4. Has had acquired immune deficiency syndrome (AIDS)-defining opportunistic infection in the past 12 months before screening.
5. Has QT interval corrected (QTc) prolongation or other significant electrocardiogram (ECG) abnormalities.
6. Has hypersensitivity to nemtabrutinib or contraindication to ibrutinib or acalabrutinib, or any of the excipients.
7. Has history of severe bleeding disorder.
8. Has history of second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
9. Has received any systemic anticancer therapy for CLL/SLL.
10. Is currently being treated with p-glycoprotein (P-gp) substrates with a narrow therapeutic index, cytochrome P450 3A (CYP3A) strong or moderate inducers or CYP3A strong inhibitors.
11. Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids.
12. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
13. Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration.
14. 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.
15. Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed.
16. Has active infection requiring systemic therapy.
17. Participants who have not adequately recovered from major surgery or have ongoing surgical complications.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Objective Response Rate (ORR) per Chronic Lymphocytic Leukemia (iwCLL) Criteria 2018 as assessed by Blinded Independent Central Review (BICR)
2. Progression-Free Survival (PFS) per iwCLL Criteria 2018 as assessed by BICR

Secondary endpoints 4

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Siyang Leng

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Siyang Leng

Third parties 9

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Application history

1 submissions — initial application plus substantial / non-substantial modifications