This is an open-label, multicentre Phase Ib study to evaluate the safety and preliminary efficacy of new generation Bruton Tyrosine Kinase inhibitor Rocbrutinib in combination to R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristin, Prednison) in adult patients with newly diagnosed, previously untreated B-cell Non-Hodgkin Lymphoma [Diffuse Large B-cell Lymphoma (DLBCL), Marginal Zone Lymphoma (MZL) or Mantle Cell Lymphoma (MCL)].

OUTLINE:

Dose escalation portion(Part A): In the dose escalation portion of the study, the escalating doses of Rocbrutinib combined with R-CHOP may be explored, using the 3+3 principle for dose determination. If dose escalation is acceptable, and subsequently will determine the recommended Phase 2 dose.

Dose expansion portion(Part B): This will be conducted as a multicenter, open-label study, including three cohorts(Cohort 1: non-GCB DLBCL; Cohort 2: MZL; Cohort 3: MCL). Eligible subjects will receive Rocbrutinib combined with R-CHOP for 6 cycles, then Rocbrutinib plus Rituximab for 2 cycles, and followed by Rocbrutinib maintenance for 2 years.

After completion of study treatment, patients are followed up every 12 weeks for 1 year, then every 24 weeks for 4 year.

PRIMARY OBJECTIVES:

I. To evaluate the safety of Rocbrutinib in combination to R-CHOP in B-cell Non-Hodgkin Lymphoma, including the maximum tolerated dose (MTD), dose limiting toxicities(DLT), adverse events (AEs), clinically significant laboratory abnormalities.

2. To determine the recommended dose. 3. To determine the pharmacokinetic characteristics of Rocbrutinib in combination to R-CHOP.

SECONDARY OBJECTIVES:

I. To determine the overall response rate, the complete response rate, duration of remission, survival outcomes (progression free survival, event free survival, overall survival) in DLBCL/ Non-germinal Center(non-GCB) DLBCL.

2. To determine the overall response rate, the complete response rate, duration of remission, survival outcomes (progression free survival, event free survival, overall survival) in MZL.

3. To determine the overall response rate, the complete response rate, duration of remission, survival outcomes (progression free survival, event free survival, overall survival) in MCL.

Inclusion Criteria:

• Participants was histopathologically diagnosed with any of the following diseases: DLBCL, MZL or MCL (if enrolled in the dose expansion phase, histological confirmation of non-GCB subtype), and have not previously received anti-tumor systemic therapy or local radiation therapy for the above diseases.
• Participants must have at least one measurable lesion.
• ECOG physical status score 0-2.
• Life expectancy ≥6 months.
• International Prognostic Index (IPI) score ≥ 2 (only participants with DLBCL in dose expansion portion).
• Adequate coagulation, liver, kidney, and hematopoietic functions：PT and APTT <1.5x ULN; serum bilirubin <1.5x ULN except in participants with Gilbert's syndrome who must have a serum bilirubin of <3x ULN, AST and ALT ≤ 3x ULN or < 5x ULN if hepatic involvement are present; serum creatinine (Scr) ≤1.5 x ULN, or calculated creatinine clearance ≥ 30ml/min by Cockcroft-Gault formula.; ANC≥1500/mm3, hemoglobin≥8.0 g/dL, and platelets >100,000/mm3 unless deemed related to lymphoma involvement in the bone marrow and felt potentially reversible by the treating physician.
• Women of childbearing potential must have a negative serum or urine (beta-human chorionic gonadotropin [beta-hCG]) at screening.
• Women of childbearing potential and men who are sexually active with a woman of childbearing potential must be practicing a highly effective contraceptive measures of during and after the study (90 days after the last dose of ROCBRUTINIB and 12 months after the last dose of Rituximab). Men must agree to not donate sperm during and for up to 90 days after he last dose of ROCBRUTINIB.
• Participants voluntarily enrolled and signed the informed consent form, and followed the trial treatment and visits.

Exclusion Criteria:

• Participants are allergic to Rocbrutinib or any of its excipients; Participants who are assessed by the investigator as being unable to tolerate the R-CHOP regimen.
• Participants with known central nervous system involvement with lymphoma. or diagnosis of primary central nervous system lymphoma (PCNSL) or primary mediastinal large B-cell lymphoma (PMBL).
• Participants with DLBCL had a history of indolent lymphoma such as FL or CLL (Richter's transformation), or was histopathologically comfirmed with FL (regardless of grade) coexistentially.
• Prior treatment with solid organ transplantation or hematopoietic stem cell transplantation(HSCT) ; expected HSCT during the study.
• Major surgery within 4 weeks of study entry or expected major surgery during the study.
• Prior another non-antitumor or medical instruments clinical trials within 4 weeks.
• Known bleeding diseases (such as von Willebrand's disease or hemophilia A, hemophilia B, etc.), or have bleeding tendency.
• Prior treatment with warfarin or equivalent vitamin K antagonists within 14 days; requires anticoagulation with warfarin or equivalent vitamin K antagonists.
• Prior treatment with strong/moderate CYP3A4 inhibitors within 5 days or prior foods with inhibitory effects on CYP3A4 within 3 days at screening; requires chronic treatment with moderate/strong CYP3A inhibitors or inducers, or OATP1B1/OATP1B3 sensitive substrates during the study.
• Participants with other malignancies other than the target indications of this study within the past three years.
• Prior treatment with the cumulative dose of doxorubicin ≥150 mg/m2 (or other anthracyclines at doses converted based on cumulative cardiac toxicity)
• Any serious medical condition including but not limited to uncontrolled hypertension, uncontrolled congestive heart failure or ≥Class 2 cardiac disease as defined by the New York Heart Association Functional Classification or LVEF less than 40%, uncontrolled or symptomatic arrhythmias with corrected QT interval (QTc) > 480 msec, uncontrolled diabetes mellitus, active/symptomatic coronary artery disease, COPD, renal failure, severe hepatic disease, uncontrolled active infection, active hemorrhage.
• Known HIV infection, or syphilis infection, or hepatitis B DNA or hepatitis C RNA positive.
• Known diseases that affect drug swallowing or absorption.
• Unfit to participate in this study in the investigator's opinion.