Nemtabrutinib With Rituximab for the Treatment of Patients With Mantle Cell Lymphoma

Exclusion Criteria

• •* HIV screening tests are not required unless:
• •* Known history of HIV infection
• •* As mandated by local health authority
• •Person of childbearing potential (POCBP): negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• •Participants assigned male sex at birth:
• •If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:
• •Nemtabrutinib: 12 days
• •Rituximab: 3 months
• •Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR
• •Uses contraception as detailed below unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel's review of the participant's medical records, medical examination, or medical history interview) as detailed below:
• •Uses a penile/external condom plus nonparticipant of childbearing potential who is not currently pregnant and should also be advised of the benefit for that partner to use an additional method of contraception, as a condom may break or leak.
• •* Note: Participants capable of producing ejaculate whose partner is pregnant or breastfeeding must agree to use penile/external condom during each episode of sexual activity in which the partner is at risk of drug exposure via ejaculate.
• •Contraceptive use by participants capable of producing sperm should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed
• •* Participants assigned female sex at birth:
• •A participant assigned female sex at birth is eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies:
• •Is not a person of childbearing potential (POCBP) OR
• •Is a POCBP and:
• •* Uses a contraceptive method that is highly effective (with a failure rate of \< 1% per year), with low user dependency, or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:
• •* Nemtabrutinib: 1 month
• •* Rituximab: 12 months
• •* The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by POCBPs should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed.
• •Has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for urine test) or 72 hours (for serum test) before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• •Abstains from breastfeeding during the study intervention period and for at least 30 days after study intervention with nemtabrutinib.
• •Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy
• •Chronic systemic corticosteroid use \> 20 mg/day of prednisone or equivalent. Patients who received corticosteroid treatment with ≤ 20 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to day 1 of cycle 1. Patients may have received a brief (≤ 14 days) course of systemic steroids (≤ 100 mg prednisone equivalent per day) prior to initiation of study therapy for control of lymphoma-related symptoms
• •History of severe bleeding disorder defined as an ongoing congenital or acquired condition that leads to an increased likelihood of bleeding
• •Unstable cardiac disease as defined by one of the following:
• •* Acute myocardial infarction (MI) within the past 6 months
• •* NYHA (New York Heart Association) heart failure class III-IV
• •* Unstable angina (angina symptoms at rest) or new-onset angina (begun within the last 3 months)
• •Corrected QT (QTc) prolongation (defined as a Fridericia's corrected QT interval \[QTcF\] \> 450 msecs) or other significant electrocardiogram (ECG) abnormalities including second degree atrioventricular (AV) block type II, third degree AV block, or bradycardia (ventricular rate less than 50 beats/min)
• •Positive for hepatitis C virus (HCV) virus by polymerase chain raction (PCR) at screening. Testing only required if the hepatitis (hep) C antibody is positive
• •AIDS-defining opportunistic infection in the past 12 months prior to screening
• •Known allergy/sensitivity (≥ grade 3) to nemtabrutinib or any of the excipients; history of allergic reactions attributed to compounds of similar chemical or biologic composition to study agents
• •Clinically significant uncontrolled illness
• •Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection (as evaluated by the investigator) within 4 weeks prior to the first study treatment
• •Primary or secondary central nervous system (CNS) lymphoma at the time of recruitment or history of CNS lymphoma
• •Other active malignancy. Exceptions include malignancy treated with curative intent and no known active disease present for ≥ 2 years prior to initiation of protocol therapy; adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease; adequately treated in situ carcinomas (e.g., cervical, esophageal, etc.) without evidence of disease; asymptomatic prostate cancer managed with "watch and wait" strategy
• •POCBP: Pregnant or breastfeeding
• •Patients with gastrointestinal dysfunction and/or clinically significant medical condition of malabsorption, inflammatory bowel disease, chronic conditions which manifest with diarrhea, refractory nausea, vomiting or any other condition that will interfere significantly with drug absorption (e.g., gastric bypass surgery, gastrectomy)
• •Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• •Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)