The Efficacy and Safety of Sonrotoclax, Zanubrutinib Combined With Obinutuzumab in MCL

A Single-Arm, Prospective Clinical Study Evaluating the Efficacy and Safety of Sonrotoclax and Zanubrutinib Combined With Obinutuzumab in the First-Line Treatment of Newly Diagnosed Intermediate-to-High-Risk Mantle Cell Lymphoma

A Single-Arm, Prospective Clinical Study Evaluating the Efficacy and Safety of Sonrotoclax, Zanubrutinib Combined with Obinutuzumab in the First-Line Treatment of Newly Diagnosed Intermediate-to-High-Risk Mantle Cell Lymphoma

Study Overview

• Status: Not yet recruiting
• Conditions: Intermediate-to-High-Risk Mantle Cell Lymphoma; the Efficacy and Safety
• Intervention / Treatment: Drug: Sonrotoclax, Zanubrutinib Combined with Obinutuzumab

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Weili Zhao; Phone Number: +86 02164370045; Email: zhao.weili@yahoo.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200000
      • Shanghai Ruijin Hospital
      • Contact: Weili Zhao; Phone Number: 021-64370045; Email: zhao.weili@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Age ≥18 years.

2. Histologically confirmed, previously untreated mantle cell lymphoma (MCL), with at least one of the following high-risk features:

   1. Blastoid or pleomorphic morphology;
   2. Ki-67 ≥30%;
   3. TP53 mutation or deletion;
   4. 17p deletion;
   5. High-risk MIPI group with an expected survival >3 months.

3. Laboratory criteria meeting the following requirements:

   1. Absolute neutrophil count ≥1,000/mm³ or ≥1.0 × 10⁹/L, platelet count ≥50,000/mm³ or ≥50 × 10⁹/L, and hemoglobin ≥8 g/dL;
   2. Creatinine clearance ≥50 mL/min (calculated using the standard Cockcroft-Gault formula);
   3. Serum albumin ≥3.0 g/dL; total bilirubin ≤1.5 × the upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN, or ≤5.0 × ULN in cases of hepatic lymphoma involvement; serum amylase or lipase ≤ULN;
   4. International normalized ratio (INR) ≤1.5 × ULN or activated partial thromboplastin time (aPTT) ≤1.5 × ULN; for patients receiving warfarin anticoagulation therapy, INR may be between 2 and 3;
   5. Cardiac function: left ventricular ejection fraction (LVEF) ≥50%.

Exclusion Criteria

1. Contraindications to any of the study drugs.
2. Known history of clinically significant liver disease, including viral or other hepatitis or cirrhosis (hepatitis B defined as positive hepatitis B core antibody [HBcAb] with HBV-DNA above the ULN; active hepatitis C defined as positive HCV antibody-patients with negative HCV-RNA may be enrolled).
3. Human immunodeficiency virus (HIV) infection.
4. Congestive heart failure (New York Heart Association [NYHA] Class >2); history of acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months prior to enrollment.
5. Congenital long QT syndrome or QTc >480 ms (QTc must be calculated using Fridericia's formula: QTcF = QT/(RR)^0.33).
6. History of other malignancies within the past 5 years, except for cured carcinoma in situ of the cervix, basal cell carcinoma of the skin, carcinoma in situ of the breast, or other second primary malignancies that were curatively treated and have had no recurrence within 5 years.
7. Pregnant or breastfeeding women, or those planning to become pregnant during the study period (fertile men and women must agree to use effective contraception during the study and for 30 days after the last dose of study treatment, such as dual-barrier methods, condoms, oral or injectable contraceptives, intrauterine devices, etc. Postmenopausal women and surgically sterilized women are exempt).
8. Prior history of significant neurological or psychiatric disorders, or history of psychotropic drug abuse or substance abuse.
9. Clinically significant active infection.
10. Inability to take oral medications, difficulty swallowing, chronic diarrhea, intestinal obstruction, or other conditions that may affect drug administration or absorption.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Sonrotoclax, Zanubrutinib Combined with Obinutuzumab treatment

Drug: Sonrotoclax, Zanubrutinib Combined with Obinutuzumab; The treatment regimen was as follows: In cycle 1 (C1), obinutuzumab 1000 mg was administered intravenously on day 1 (D1); sotoroclax was given at 80 mg on D2, 160 mg on D3, and 320 mg on D4; zanubrutinib was administered at 160 mg twice daily (BID). Each cycle was defined as 28 days. From cycles 2 to 6 (C2-C6), patients received obinutuzumab 1000 mg intravenously on D1, sotoroclax 320 mg once daily, and zanubrutinib 160 mg BID.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate	The percentage of participants with a complete response at the end of Cycle 6 was determined on the basis of investigator assessments according to the Lugano Classification for Response Criteria in Lymphoma	At the end of Cycle 6 (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival (OS) was measured from the date of diagnosis to the date of death or the last follow-up.	2 years after enrollment
Overall response rate	The percentage of participants with overall response was determined on the basis of investigator assessments according to the Lugano Classification for Response Criteria in Lymphoma	Overall Response Rate At the end of Cycle 6 (each cycle is 28 days)
Progression free survival	Progression-free survival was defined as the time from the date of diagnosis until the date of the first documented day of disease progression or relapse, or death from any cause, whichever occurred first.	2 years after enrollment
Treatment-Related Adverse Events	An adverse event is any untoward medical occurrence in a participant receiving a pharmaceutical product that does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease that is temporally associated with the use of a pharmaceutical product, whether or not it is considered related to the pharmaceutical product. Preexisting conditions that worsen during a study are also considered adverse events. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.	From enrollment to study completion, a maximum of 3 years.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma circulating tumor DNA (ctDNA) levels	Exploratory biomarker of ctDNA to predict treatment response and survival	From enrollment to study completion, a maximum of 3 years

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 20, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): March 1, 2029

Study Registration Dates

• First Submitted: March 29, 2026
• First Submitted That Met QC Criteria: April 21, 2026
• First Posted (Actual): April 23, 2026

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: obinutuzumab
• Other Study ID Numbers: Solide

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No