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

Phase 3

• Conditions: C911 Chronic lymphocytic leukaemia of B-cell type; Chronic lymphocytic leukaemia of B-cell type; C911

• Registration Number: PER-046-23
• Lead Sponsor: Merck Sharp & Dohme LLC., (una subsidiaria de Merck & Co. Inc.)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-06-06
• Last Update Posted: 20 August 2024

Recruitment & Eligibility

• Status: Without startig enrollment
• Sex: All
• Target Recruitment: 0

Inclusion Criteria

Type of Participant and Disease Characteristics: Confirmed diagnosis of CLL/SLL and active disease clearly documented to have a need to initiate therapy. At least 1 of the following criteria should be met:
-Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia and/or thrombocytopenia. Cutoff levels of Hb <10 g/dL or platelet counts <100 × 109/L are generally regarded as indication for treatment. However, in some participants, platelet counts <100 × 109/L may remain stable over a long period; this situation does not automatically require therapeutic intervention.
-Massive (ie, =6 cm below the left costal margin) or progressive or symptomatic splenomegaly.
-Massive nodes (ie, =10 cm in longest diameter) or progressive or symptomatic lymphadenopathy.
-Progressive lymphocytosis with an increase of =50% over a 2-month period, or LDT <6 months. LDT can be obtained by linear regression extrapolation of ALCs obtained at intervals of 2 weeks over an observation period of 2 to 3 months; participants with initial blood lymphocyte counts <30 × 109/L may require a longer observation period to determine the LDT. Factors contributing to lymphocytosis other than CLL (eg, infections, steroid administration) should be excluded.
-Autoimmune complications including anemia or thrombocytopenia poorly responsive to corticosteroids, as deemed by the investigator.
-Symptomatic or functional extranodal involvement (eg, skin, kidney, lung, spine).
-Disease-related symptoms as defined by any of the following:
oUnintentional weight loss =10% within the previous 6 months.
oSignificant fatigue (cannot work or unable to perform usual activities).
oFever of 100.5 °F or 38.0 °C for 2 or more weeks without evidence of infection.
oNight sweats for =1 month without evidence of infection.

Type of Participant and Disease Characteristics: At least 1 of the following markers of disease burden:
-Malignant lymph nodes attributable to CLL/SLL, which are clearly and reproducibly measurable in 2 dimensions in the axial plane, and measure >1.5 cm in longest diameter when assessed by CT/MRI scan.
-Absolute lymphocyte count >4 × 109/l.
-Platelet count <100 × 109/l.
-Hemoglobin <11 g/dL

Type of Participant and Disease Characteristics: Provision of peripheral blood, bone marrow aspirate, and/or a lymph node sample as specified in the SoA (Section 1.3.1) and Appendix 13 for determination of del(17p) status and TP53 mutation status, both determined by central testing. This is required before randomization.
-Del(17p) indeterminate is eligible only if TP53 mutation is present.
-TP53 indeterminate is eligible only if del(17p) is detected.

Type of Participant and Disease Characteristics: An ECOG PS of 0 to 2 within 7 days before randomization.

Type of Participant and Disease Characteristics: The ability to swallow and retain oral medication.
NOTE: Administration of nemtabrutinib is not permitted through a J-PEG tube.

Type of Participant and Dis

Exclusion Criteria

Medical Conditions: History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
NOTE: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder.

Medical Conditions: Active HBV/HCV infection. See Inclusion Criteria 6 (HBV) and 7 (HCV) for requirements.

Medical Conditions: Gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy).

Medical Conditions: Diagnosis of Richter Transformation or active CNS involvement by CLL/SLL.

Medical Conditions: AIDS-defining opportunistic infection in the past 12 months before screening.

Medical Conditions: 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).

Medical Conditions: Hypersensitivity to nemtabrutinib or contraindication to ibrutinib or acalabrutinib (eg, Child-Pugh Class C hepatic impairment), or any of the excipients.
NOTE: Refer to the IB for details regarding excipients for nemtabrutinib and the current prescribing information for ibrutinib or acalabrutinib.

Medical Conditions: History of severe bleeding disorder.

Prior/Concomitant Therapy: Has received any systemic anticancer therapy for CLL/SLL

Prior/Concomitant Therapy: Currently being treated with the following drugs:
a.P-gp substrates with a narrow therapeutic index
b.CYP3A strong inducers
c.CYP3A strong inhibitors
-CYP3A moderate inhibitors are not excluded, but coadministration with ibrutinib or acalabrutinib may require dose modifications.
-Consult the current version of the relevant prescribing information as stated in Section 6.6.2.
NOTE:
-A washout period of at least 5 times the half-life after the last dose of any of the above treatments is required for a participant to be eligible for study enrollment.
-Refer to Section 6.5 and Appendix 8 regarding prohibited concomitant

Study & Design

• Study Type: Interventional
• Study Design: Not specified