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

NCT06251180 | Recruiting Phase 1

• 1 other identifier: LP-168-CN301
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

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 \[Diffuse Large B-cell Lymphoma (DLBCL), Marginal Zone Lymphoma (MZL) or Mantle Cell Lymphoma (MCL)\].

Conditions

B-cell Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (9)

• MTD

  Standard phase I 3+3 design.

  Up to 21 days after the initial dose

• Recommended Dose

  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

  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

  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

  Maximum plasma concentration (Cmax) of Rocbrutinib.

  Up to 24 hours post dose

• Tmax of Rocbrutinib

  Time to maximum plasma concentration (Tmax) of Rocbrutinib.

  Up to 24 hours post dose

• T1/2 of Rocbrutinib

  The terminal elimination half-life (t1/2).

  Up to 24 hours post dose

• AUC0-t of Rocbrutinib

  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

  Apparent clearance (CL/F) of Rocbrutinib.

  Up to 24 hours post dose

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  Evey 2 cycles for 8 cycles, and followed every 3cyles for 24 months

• Complete remission (CR)

  Evey 2 cycles for 8 cycles, and followed every 3cyles for 24 months

• Duration of Response(DOR)

  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)

  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.

• Event-free Survival (EFS)

  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.

Study Arms (4)

Dose Escalation

EXPERIMENTAL

Patients with DLBCL or MCL or MZL receive Rocbrutinib（at escalating dose）+R-CHOP

Drug: Rocbrutinib; Biological: Rituximab; Drug: Cyclophosphamide; Drug: doxorubicin; Drug: Vincristin; Drug: Prednisone

Dose Expansion [non-GCB DLBCL]

EXPERIMENTAL

Patients with non-GCB DLBCL receive Rocbrutinib（at recommended dose )+R-CHOP

Drug: Rocbrutinib; Biological: Rituximab; Drug: Cyclophosphamide; Drug: doxorubicin; Drug: Vincristin; Drug: Prednisone

Dose Expansion [MCL]

EXPERIMENTAL

Patients with MCL receive Rocbrutinib（at recommended dose )+R-CHOP

Drug: Rocbrutinib; Biological: Rituximab; Drug: Cyclophosphamide; Drug: doxorubicin; Drug: Vincristin; Drug: Prednisone

Dose Expansion [MZL]

EXPERIMENTAL

Patients with MZL receive Rocbrutinib（at recommended dose )+R-CHOP

Drug: Rocbrutinib; Biological: Rituximab; Drug: Cyclophosphamide; Drug: doxorubicin; Drug: Vincristin; Drug: Prednisone

Interventions

Rocbrutinib DRUG

orally once daily in a 21-day cycle for eight cycles, and as maintenance for 2 years.

Also known as: LP-168

Dose Escalation; Dose Expansion [MCL]; Dose Expansion [MZL]; Dose Expansion [non-GCB DLBCL]

Rituximab BIOLOGICAL

375 mg/m2 administered intravenously once on Day 1 in a 21-day cycle for eight cycles.

Also known as: MabThera; Rituximab Biosimilar HLX01; Rituximab biosimilar TQB2303; Henlius; Halpryza

Dose Escalation; Dose Expansion [MCL]; Dose Expansion [MZL]; Dose Expansion [non-GCB DLBCL]

Cyclophosphamide DRUG

750 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.

Also known as: CTX

Dose Escalation; Dose Expansion [MCL]; Dose Expansion [MZL]; Dose Expansion [non-GCB DLBCL]

doxorubicin DRUG

50 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.

Also known as: ADM; Adriamycin; DOX; Doxorubin hydrochloride

Dose Escalation; Dose Expansion [MCL]; Dose Expansion [MZL]; Dose Expansion [non-GCB DLBCL]

Vincristin DRUG

1.4 mg/m2 administered intravenously once on Day 1 or 2 in a 21-day cycle for six cycles.

Also known as: VCR; Vincrystine

Dose Escalation; Dose Expansion [MCL]; Dose Expansion [MZL]; Dose Expansion [non-GCB DLBCL]

Prednisone DRUG

100 mg orally once on Day 1 to Day 5 in a 21-day cycle for six cycles.

Also known as: delta.1-Cortisone; 1, 2-Dehydrocortisone

Dose Escalation; Dose Expansion [MCL]; Dose Expansion [MZL]; Dose Expansion [non-GCB DLBCL]

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Guangzhou Lupeng Pharmaceutical Company LTD.: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (2)

• Younes A, Sehn LH, Johnson P, Zinzani PL, Hong X, Zhu J, Patti C, Belada D, Samoilova O, Suh C, Leppa S, Rai S, Turgut M, Jurczak W, Cheung MC, Gurion R, Yeh SP, Lopez-Hernandez A, Duhrsen U, Thieblemont C, Chiattone CS, Balasubramanian S, Carey J, Liu G, Shreeve SM, Sun S, Zhuang SH, Vermeulen J, Staudt LM, Wilson W; PHOENIX investigators. Randomized Phase III Trial of Ibrutinib and Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Non-Germinal Center B-Cell Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2019 May 20;37(15):1285-1295. doi: 10.1200/JCO.18.02403. Epub 2019 Mar 22.

  PMID: 30901302 BACKGROUND

• Younes A, Thieblemont C, Morschhauser F, Flinn I, Friedberg JW, Amorim S, Hivert B, Westin J, Vermeulen J, Bandyopadhyay N, de Vries R, Balasubramanian S, Hellemans P, Smit JW, Fourneau N, Oki Y. Combination of ibrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for treatment-naive patients with CD20-positive B-cell non-Hodgkin lymphoma: a non-randomised, phase 1b study. Lancet Oncol. 2014 Aug;15(9):1019-26. doi: 10.1016/S1470-2045(14)70311-0. Epub 2014 Jul 17.

  PMID: 25042202 BACKGROUND

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Qingqing Cai, Ph D

  Sun Yat-sen University

  STUDY CHAIR

Central Study Contacts

Yue Shen, Ph D

CONTACT

86-020-31605119; yshen@lupengbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2024
• First Posted: February 9, 2024
• Study Start: April 10, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2029
• Last Updated: March 25, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)