Clinical trial NCT06463691: Sonrotoclax, Zanubrutinib and CD20mab in Untreated MCL Patients
Official title: An Open-label, Multi-center, Single-arm Study to Evaluate the Efficacy and Safety of Sonrotoclax, Zanubrutinib and CD20mab in Untreated MCL Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: MCL
Keywords: MCL
Sonrotoclax
Zanubrutinib
Lead sponsor: Tianjin Medical University Cancer Institute and Hospital
Sponsor class: OTHER
First posted: 2024-06-18
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Sonrotoclax, Zanubrutinib and CD20mab
Primary purpose: TREATMENT

Brief summary: This is a an open-label, multi-center, single-arm study to evaluate the efficacy and safety of sonrotoclax, zanubrutinib and CD20mab in untreated MCL patients.

Detailed description: The benefits of efficacy and survival of immunotherapy regimen in TN MCL is limited, and not all patients are fit for receiving chemotherapy. Considering the balance of toxicity and efficacy, a chemo-free regimen will be a trend in 1L MCL patients. The study is to explore the sonrotoclax, zanubrutinib and CD20mab combination regimen for TN MCL.

Eligibility criteria: Inclusion Criteria:

1. Subject must be ≥ 18 years of age.
2. Subject must have a confirmed Mantle Cell Lymphoma (MCL) diagnosis according to WHO (2008) criteria.
3. Previously untreated MCL
4. Subject has an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2.
5. Nonsterile men and women of child-bearing potential must agree to use highly effective contraceptives (e.g., condoms, implants, injectables, combined oral contraceptives, intrauterine devices, sexual abstinence, or sterilized partner) while on study; this should be maintained for 90 days after the last dose of study drug.
6. Subject must have adequate bone marrow function at Screening as follows:

   a.Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L (neutropenia due to marrow infiltration may be supported by growth factors);

   • b. Platelets ≥ 75,000/mm3 (or ≥ 50,000/mm3 for patients with bone marrow involvement of lymphoma) within 7 days
7. Subject must have adequate coagulation, renal, and hepatic function, per laboratory reference range at Screening as follows:

   1. aPTT and PT not to exceed 1.5 × the upper limit of normal (ULN); Serum creatinine not to exceed 2 x ULN, and a calculated creatinine clearance of at least 50 mL/min using the Cockcroft-Gault equation or a 24-hour urine collection;
   2. AST or ALT ≤ 3.0 × the upper normal limit (ULN) of institution's normal range; Bilirubin ≤ 1.5 × ULN. Subjects with documented Gilbert's Syndrome may have a bilirubin \> 1.5 × ULN.
8. Written informed consent form according to GCP and national regulations.

Exclusion Criteria:

1. Subject has known central nervous system involvement by MCL.
2. Prior malignancy other than MCL within the past 3 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score 6 prostate cancer.
3. Receiving any treatment with a moderate CYP3A4 inhibitor or strong CYP3A4 inhibitor or inducer within 2 weeks (or 5 half-lives, whichever is longer) before the first dose of study drug or requiring long-term use of strong CYP3A4 inhibitors or inducers.
4. Prior ASCT within the last 3 months; or prior autologous chimeric antigen receptor-T cell therapy within the last 3 months; or prior allogeneic stem cell transplant within the last 6 months or currently has an active graft-vs-host disease requiring the use of immunosuppressants.
5. Major surgery within 4 weeks of screening.
6. Clinically significant cardiovascular disease including the following:

   1. Myocardial infarction within 6 months before screening
   2. Unstable angina within 3 months before screening
   3. New York Heart Association class III or IV congestive heart failure
   4. History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation)
   5. QT interval corrected based on Fridericia's formula (QTcF) \> 480 msec.
   6. History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place
   7. Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements showing systolic blood pressure \> 170 mmHg and diastolic blood pressure \> 105 mmHg at screening.
7. Prior exposure to a BCL2 inhibitor (e.g., venetoclax/ABT-199).
8. Prior exposure to a BTK inhibitor (e.g., ibrutinib, zanubrutinib).
9. History of hypersensitivity to excipient(s) of the sonrotoclax tablet.
10. Patients with unresolved hepatitis B or C infection or known HIV-positive infection：

    1. Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable (\< 20 IU/mL), and if they are willing to undergo monitoring for HBV reactivation.
    2. Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable (\< 15 IU/mL), and if they are willing to undergo monitoring for HCV reactivation.
11. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
12. Pregnant or lactating women.
13. History of stroke or intracranial hemorrhage within 6 months before the first dose of study drug.
14. Underlying medical conditions that, in the investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of safety or efficacy results.

Primary outcomes:
measure: CR (complete response) rate at cycle 12 by investigator (INV).
timeFrame: From enrollment to the end of treatment at the end of cycle 12 (each cycle is 28 days)
Secondary outcomes:
measure: ORR (Overall response rate)
timeFrame: From enrollment to the end of treatment at the end of cycle 36 (each cycle is 28 days)
measure: Overall survival (OS)
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
Study officials:
References: