Phase Ib Study of Rocbrutinib in Combination with R-CHOP in Patients with Newly Diagnosed B-cell Non-Hodgkin Lymphoma

March 21, 2025 updated by: Guangzhou Lupeng Pharmaceutical Company LTD.

A Phase Ib Study to Assess Safety and Preliminary Efficacy of Rocbrutinib in Combination with R-CHOP in Patients with Newly Diagnosed B-NHL

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)].

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

112

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510060
        • Recruiting
        • Sun Yat-sen University Cancer Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation
Patients with DLBCL or MCL or MZL receive Rocbrutinib（at escalating dose）+R-CHOP
Drug: Rocbrutinib
orally once daily in a 21-day cycle for eight cycles, and as maintenance for 2 years.
Other Names:
  • LP-168
Biological: Rituximab
375 mg/m2 administered intravenously once on Day 1 in a 21-day cycle for eight cycles.
Other Names:
  • MabThera; Rituximab Biosimilar HLX01; Rituximab biosimilar TQB2303; Henlius; Halpryza
Drug: Cyclophosphamide
750 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.
Other Names:
  • CTX
Drug: doxorubicin
50 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.
Other Names:
  • ADM; Adriamycin; DOX; Doxorubin hydrochloride
Drug: Vincristin
1.4 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.
Other Names:
  • VCR; Vincrystine
Drug: Prednisone
100 mg orally once on Day 1 to Day 5 in a 21-day cycle for six cycles.
Other Names:
  • delta.1-Cortisone; 1, 2-Dehydrocortisone
Experimental: Dose Expansion [non-GCB DLBCL]
Patients with non-GCB DLBCL receive Rocbrutinib（at recommended dose )+R-CHOP
Drug: Rocbrutinib
orally once daily in a 21-day cycle for eight cycles, and as maintenance for 2 years.
Other Names:
  • LP-168
Biological: Rituximab
375 mg/m2 administered intravenously once on Day 1 in a 21-day cycle for eight cycles.
Other Names:
  • MabThera; Rituximab Biosimilar HLX01; Rituximab biosimilar TQB2303; Henlius; Halpryza
Drug: Cyclophosphamide
750 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.
Other Names:
  • CTX
Drug: doxorubicin
50 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.
Other Names:
  • ADM; Adriamycin; DOX; Doxorubin hydrochloride
Drug: Vincristin
1.4 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.
Other Names:
  • VCR; Vincrystine
Drug: Prednisone
100 mg orally once on Day 1 to Day 5 in a 21-day cycle for six cycles.
Other Names:
  • delta.1-Cortisone; 1, 2-Dehydrocortisone
Experimental: Dose Expansion [MCL]
Patients with MCL receive Rocbrutinib（at recommended dose )+R-CHOP
Drug: Rocbrutinib
orally once daily in a 21-day cycle for eight cycles, and as maintenance for 2 years.
Other Names:
  • LP-168
Biological: Rituximab
375 mg/m2 administered intravenously once on Day 1 in a 21-day cycle for eight cycles.
Other Names:
  • MabThera; Rituximab Biosimilar HLX01; Rituximab biosimilar TQB2303; Henlius; Halpryza
Drug: Cyclophosphamide
750 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.
Other Names:
  • CTX
Drug: doxorubicin
50 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.
Other Names:
  • ADM; Adriamycin; DOX; Doxorubin hydrochloride
Drug: Vincristin
1.4 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.
Other Names:
  • VCR; Vincrystine
Drug: Prednisone
100 mg orally once on Day 1 to Day 5 in a 21-day cycle for six cycles.
Other Names:
  • delta.1-Cortisone; 1, 2-Dehydrocortisone
Experimental: Dose Expansion [MZL]
Patients with MZL receive Rocbrutinib（at recommended dose )+R-CHOP
Drug: Rocbrutinib
orally once daily in a 21-day cycle for eight cycles, and as maintenance for 2 years.
Other Names:
  • LP-168
Biological: Rituximab
375 mg/m2 administered intravenously once on Day 1 in a 21-day cycle for eight cycles.
Other Names:
  • MabThera; Rituximab Biosimilar HLX01; Rituximab biosimilar TQB2303; Henlius; Halpryza
Drug: Cyclophosphamide
750 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.
Other Names:
  • CTX
Drug: doxorubicin
50 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.
Other Names:
  • ADM; Adriamycin; DOX; Doxorubin hydrochloride
Drug: Vincristin
1.4 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.
Other Names:
  • VCR; Vincrystine
Drug: Prednisone
100 mg orally once on Day 1 to Day 5 in a 21-day cycle for six cycles.
Other Names:
  • delta.1-Cortisone; 1, 2-Dehydrocortisone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MTD
Time Frame: Up to 21 days after the initial dose
Standard phase I 3+3 design.
Up to 21 days after the initial dose
Recommended Dose
Time Frame: Up to 1.5 years
Recommended Dose will be determined using available safety and pharmacokinetics data upon completion of the dose escalation phase.
Up to 1.5 years
Incidence of AEs
Time Frame: From first dose of study drug to 28 days after the last dose of study drugs
Type, frequency and severity of AEs, relationship of AEs to study treatment Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 Type, frequency and severity of AEs, relationship of AEs to study treatment Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0
From first dose of study drug to 28 days after the last dose of study drugs
Incidence of clinically significant laboratory abnormalities
Time Frame: From first dose of study drug to 28 days after last dose of study drug
Clinically significant abnormalities in hematology, chemistry, coagulation and urinalysis.
From first dose of study drug to 28 days after last dose of study drug
Cmax of Rocbrutinib
Time Frame: Up to 24 hours post dose
Maximum plasma concentration (Cmax) of Rocbrutinib.
Up to 24 hours post dose
Tmax of Rocbrutinib
Time Frame: Up to 24 hours post dose
Time to maximum plasma concentration (Tmax) of Rocbrutinib.
Up to 24 hours post dose
T1/2 of Rocbrutinib
Time Frame: Up to 24 hours post dose
The terminal elimination half-life (t1/2).
Up to 24 hours post dose
AUC0-t of Rocbrutinib
Time Frame: Up to 24 hours post dose
Area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration of Rocbrutinib.
Up to 24 hours post dose
CL/F of Rocbrutinib
Time Frame: Up to 24 hours post dose
Apparent clearance (CL/F) of Rocbrutinib.
Up to 24 hours post dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free Survival (EFS)
Time Frame: Measured from the date of first dose to the date of earliest evidence of disease progression, initiation of new non-protocol-specified antitumor therapy without documented progression, death, and for up to 5 years after the last subject is enrolled.
EFS is defined as the number of days from the date of first dose to the date of earliest evidence of disease progression/relapse, or initiation of new non-protocol-specified antitumor therapy without documented progression, or death.
Measured from the date of first dose to the date of earliest evidence of disease progression, initiation of new non-protocol-specified antitumor therapy without documented progression, death, and for up to 5 years after the last subject is enrolled.
Objective Response Rate (ORR)
Time Frame: Evey 2 cycles for 8 cycles, and followed every 3cyles for 24 months
Assessment using the Lugano Response Criteria for Malignant Lymphoma.
Evey 2 cycles for 8 cycles, and followed every 3cyles for 24 months
Complete remission (CR)
Time Frame: Evey 2 cycles for 8 cycles, and followed every 3cyles for 24 months
Assessment using the Lugano Response Criteria for Malignant Lymphoma.
Evey 2 cycles for 8 cycles, and followed every 3cyles for 24 months
Duration of Response(DOR)
Time Frame: Measured from the date of the first remission to the date of earliest disease progression or death, and assessed up to 5 years.
DOR is defined as the number of days from the date of the first remission to the date of earliest disease progression or death.
Measured from the date of the first remission to the date of earliest disease progression or death, and assessed up to 5 years.
Progression-Free Survival(PFS)
Time Frame: Measured from the date of first dose of study drug to the date of earliest disease progression or death or last visit, and assessed up to 5 years.
PFS is defined as the number of days from the date of the first dose of study drug to the date of earliest disease progression or death.
Measured from the date of first dose of study drug to the date of earliest disease progression or death or last visit, and assessed up to 5 years.
Overall survival (OS)
Time Frame: Measured from the date of date of first dose to the date of death or last visit, and for up to 5 years after the last subject is enrolled.
OS is defined as the number of days from the date of first dose to the date of death.
Measured from the date of date of first dose to the date of death or last visit, and for up to 5 years after the last subject is enrolled.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Guangzhou Lupeng Pharmaceutical Company LTD.

Investigators

  • Study Chair: Qingqing Cai, Ph D, Sun Yat-sen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 10, 2024

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2029

Study Registration Dates

First Submitted

February 1, 2024

First Submitted That Met QC Criteria

February 1, 2024

First Posted (Actual)

February 9, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 21, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LP-168-CN301

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on B-cell Non-Hodgkin Lymphoma

Clinical Trials on Rocbrutinib

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Jamaica

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe